An extract of neem leaves reduces anxiety without causing motor side effects in an experimental model.

Anxiety modulation often requires pharmaceutical intervention, and though effective in the short-term, benzodiazepines may cause impaired motor function. As a potential alternative, anxiety-modulating effects of a neem leaf (Azadirachta indica, A Juss) extract were investigated using ethological analysis of rat behaviour on an elevated X maze and compared with diazepam treatment. Sexually immature female Sprague-Dawley rats received 0.07 or 7 mg/kg neem leaf steroidal extract, a sham injection, a 1% DMSO/saline vehicle, 2 mg/kg diazepam or no treatment one hour prior to a recorded five-minute exploration of the elevated X maze. Neem matched diazepam in anxiety reduction as both treatments caused a decrease in per cent protected stretched-attend postures (PPSAP). Neem treatment had no effect on closed arm entries or total rears, distinguishing it pharmacologically from diazepam which resulted in a predictable decrease in those locomotor measures. Whereas both neem and diazepam reduced anxiety in complex ethological behavioural indices, only neem produced anxiolysis without motor deficiency.

Role of neutrophil elastase in LTB4-induced neutrophil transmigration in vivo assessed with a specific inhibitor and neutrophil elastase deficient mice.

BACKGROUND AND PURPOSE: The serine protease neutrophil elastase (NE) appears to regulate inflammatory responses at multiple levels but its role in leukocyte transmigration in vivo remains unclear. The present study aimed to address this issue by using both an NE inhibitor (ONO-5046) and NE deficient (NE(-/-)) mice. EXPERIMENTAL APPROACH: A number of inflammatory mediators (LTB(4), KC and PAF) were investigated in vitro for their ability to stimulate the release and the surface expression of NE by neutrophils. In addition, the role of NE in leukocyte migration elicited by topical LTB(4) was investigated in vivo in mouse cremasteric venules as observed by intravital microscopy. KEY RESULTS: Amongst the mediators tested in vitro, LTB(4) was found to be a highly potent and efficacious inducer of NE cell surface expression on murine neutrophils. Furthermore, in wild-type mice (WT), LTB(4)-induced leukocyte transmigration was reduced by intravenous ONO-5046 (66% inhibition), an effect that appeared to occur at the level of the perivascular basement membrane. Interestingly, LTB(4)-induced responses were normal in NE(-/-) mice and, while ONO-5046 had no inhibitory effect in these animals, the broad-spectrum serine protease inhibitor aprotinin suppressed leukocyte transmigration in both WT and NE(-/-) mice. CONCLUSIONS AND IMPLICATIONS: The findings demonstrate the potent ability of LTB(4) to induce cell-surface expression of NE and provide evidence for the involvement of NE in LTB(4)-induced neutrophil transmigration in vivo. The results also suggest the existence of compensatory mechanisms in NE(-/-) mice, highlighting the added value of investigating pharmacological blockers in parallel with genetic deletion.

Regulation of blood pressure in the land crab Cardisoma guanhumi.

We examined the cardiovascular responses to acute and chronic changes in blood volume (BV) in the land crab Cardisoma guanhumi. Acute reduction in BV caused an increase in activity in the dorsoventral muscles (DVMs) and to a lesser extent in the epimeral attractor muscles (EAMs). Contraction of the DVMs and EAMs will decrease the volume of the dorsal sinus and the thorax as a whole, respectively. BV reduction also caused bradycardia with frequent periods of cardiac arrest. There was a small drop in hemolymph pressure. BV expansion had the reciprocal effect on DVM and EAM activity but had no effect on heart rate (fH). After the cardioregulatory nerves were cut, acute hypovolemia had no effect on fH but still caused a moderate increase in DVM activity. After dehydration-induced BV reduction, DVM activity increased, whereas hemolymph pressure, fH, and EAM activity were maintained close to control levels.

Cold-induced elevation of forearm vascular resistance is inversely related to birth weight.

Fetal growth retardation has been linked to elevated blood pressure in adult life. This association between birth weight and blood pressure is present in childhood and is amplified with age. However, the mechanisms that underlie this association are largely unknown. We examined the relationship between birth weight and forearm vascular resistance and forearm blood flow in children aged 9-12.7 years. A total of 58 children were randomly selected from a cohort of 1610 born at the University Hospital of the West Indies in Jamaica where adequate antenatal and delivery records were available. Blood pressure, heart rate and forearm blood flow (by venous occlusion plethysmography) were measured at rest and after cold pressor and mental arithmetic tests. There was a significant inverse correlation between birth weight and the change in the vascular resistance for the cold pressor test (r=-0.47; P<0.001) and the mental arithmetic stress test (r=-0.26; P=0.05). The log ratio of vascular resistance under stress to resting decreased by 0.289 units per kg of birth weight (95% CI: 0.145-0.434; P=0.0002). Lower birth weight is associated with increased vascular responsiveness. Increased vascular resistance might be one mechanism linking fetal growth to subsequent elevated blood pressure.

Divergent mechanisms of action of the inflammatory cytokines interleukin 1-beta and tumour necrosis factor-alpha in mouse cremasteric venules.

1. Protein synthesis dependency and the role of endogenously generated platelet activating factor (PAF) and leukotriene B(4) (LTB(4)) in leukocyte migration through interleukin-1beta (IL-1beta)- and tumour necrosis factor-alpha (TNFalpha)-stimulated mouse cremasteric venules was investigated using established pharmacological interventions and the technique of intravital microscopy. 2. Based on previously obtained dose-response data, 30 ng rmIL-1beta and 300 ng rmTNFalpha were injected intrascrotally (4 h test period) to induce comparable levels of leukocyte firm adhesion and transmigration in mouse cremasteric venules. 3. Co-injection of the mRNA synthesis inhibitor, actinomycin D (0.2 mg kg(-1)), with the cytokines significantly inhibited firm adhesion (49+/-13.6%) and transmigration (67.2+/-4.2%) induced by IL-1beta, but not TNFalpha. 4. In vitro, TNFalpha (1-100 ng ml(-1)), but not IL-1beta, stimulated L-selectin shedding and increased beta(2) integrin expression on mouse neutrophils, as quantified by flow cytometry. 5. The PAF receptor antagonist, UK-74,505 (modipafant, 0.5 mg kg(-1), i.v.), had no effect on adhesion induced by either cytokine, but significantly inhibited transmigration induced by IL-1beta (66.5+/-4.5%). 6. The LTB(4) receptor antagonist, CP-105,696 (100 mg kg(-1), p.o.), significantly inhibited both IL-1beta induced adhesion (81.4+/-15.2%) and transmigration (58.7+/-7.2%), but had no effect on responses elicited by TNFalpha. Combined administration of the two antagonists had no enhanced inhibitory effects on responses induced by either cytokine. 7. The data indicate that firm adhesion and transmigration in mouse cremasteric venules stimulated by IL-1beta, but not TNFalpha, is protein synthesis dependent and mediated by endogenous generation of PAF and LTB(4). Additionally, TNFalpha but not IL-1beta, can directly stimulate mouse neutrophils in vitro. The findings provide further evidence to suggest divergent mechanisms of actions of IL-1beta and TNFalpha, two cytokines often considered to act via common molecular/cellular pathways.

A molecular phylogeny of the Octopoda (Mollusca: Cephalopoda) evaluated in light of morphological evidence.

In this paper we examine the phylogenetic relationships of the Octopoda utilizing molecular sequence data from the cytochrome c oxidase subunit I (COI) gene and compare results from analyses of molecular data with classifications and phylogenies based on previous morphological studies. Partial COI sequences (657 bp, excluding primers) were obtained from 28 species representing most of the diversity in the Order Octopoda, along with a sequence from the established sister taxon to the Octopoda, Vampyroteuthis infernalis. Our results exhibit a number of basic differences from inferences based on standard morphological data. We attempt to resolve these differences based on our confidence in various morphological features. An important finding is the failure of the molecular data to support the monophyly of the Octopodidae. This family contains over 90% of the species in the Suborder Incirrata and has always been difficult to define. Statistical tests constraining Octopodidae monophyly by use of parsimony and maximum-likelihood techniques suggest that all incirrates may be derived from octopodids.

Motor pathway analysis in HAM/TSP using magnetic stimulation and F-waves.

BACKGROUND: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (HAM/TSP) is a chronic, progressive myelopathy endemic to the Caribbean. In HAM/TSP, peripheral motor pathways have been assessed using electromyography and nerve conduction studies; central motor pathways have been assessed to a limited extent using electrocortical stimulation. We used magnetic cortical stimulation (a painless alternative to electrocortical stimulation) and F-wave analysis to study conduction in the central and peripheral motor pathways in 18 HTLV-I seropositive, Jamaican TSP patients (ages 29-70 years; duration of symptoms 3-20 years) and 22 normal controls. METHODS: Magnetic cortical stimulation was effected using a 9 cm diameter undamped MES10 coil. F-waves and M-responses were elicited by electrical stimulation of the ulnar nerve at the wrist, and deep peroneal stimulation at the knee. Stimulation and recording of response latencies in abductor digitii minimi (ADM) and tibialis anterior (TA) were carried out using a Cadwell Excel system. RESULTS: With cortical stimulation, response latencies (TMCTs) to ADM and TA were prolonged in the patients relative to controls. F-wave and M-response latencies were unaffected, suggesting no peripheral pathology. Latency (CMCT) between cortex and lumbar cord was significantly prolonged; that between cortex and C7/T1, also, but less markedly (P < 0.0005). Amplitudes of cortically evoked responses were significantly reduced only in the lower limbs (TA). CMCT increased as the disease progressed from mild to moderate, thereafter remaining largely unchanged. CONCLUSIONS: Meta-analysis of interlaboratory control data revealed no significant differences in TMCTs between our controls and others studied using similar techniques. The observations are consistent with pathology affecting mainly the thoracolumbar cord in HAM/TSP.

Evolution of the Martian water cycle.

The current Martian water cycle is extremely asymmetric, with large amounts of vapor subliming off a permanent north polar water ice cap in northern summer, but with no apparent major source of water vapor in the southern hemisphere. Detailed simulations of this process with a three-dimensional circulation model indicate that the summertime interhemispheric exchange (Hadley cell) is very much stronger than transport by eddies in other seasons. As a result, water ice would be distributed globally were it not for the buffering action of regolith soil adsorption which limits the net flux of water vapor off the north polar cap to amounts that are insignificant even on the scale of thousands of years. It has been suggested that the polar layered deposits are the result of exchange on these long time scales, driven by changes in Martian orbital parameters. We therefore are conducting simulations to test the effect of varied orbital parameters on the Martian water cycle. We find that when the perihelion summer pole is charged with a polar water ice cap, large quantities of water are quickly transfered to the aphelion summer pole, setting up an annual cycle that resembles the present one. Thus, the adsorptivity of the Martian regolith may be in the narrow range where it can limit net transport from the aphelion but not the perihelion pole.

Disturbed anal sphincter function following vaginal delivery.

BACKGROUND: Recently interest in idiopathic (neurogenic) faecal incontinence has swung from denervation of the external anal sphincter to the internal sphincter. AIMS: To evaluate the effects of vaginal delivery on the internal sphincter. SUBJECTS: 1372 mothers were studied antenatally and 1202 were accepted into the study. METHODS: Sphincter pressures were measured antenatally, in the early postnatal period, and six to 10 weeks later in selected patients. RESULTS: 755 of 1202 subjects assessed antenatally were primiparous women and 447 multiparous women. Some 320 previous spontaneous vaginal deliveries (SVD) (mean 59 mm Hg) and 67 previous forceps deliveries (mean 58 mm Hg) had lower resting pressures than 755 primiparous women (mean 66 mm Hg) (p < 0.01). A total of 493 subjects were reassessed postnatally. There were 372 SVDs, 47 vacuum extractions, 20 forceps, and 54 caesarean deliveries. All vaginal deliveries but not caesarean sections dropped their resting anal pressures from antenatal values (p < 0.001). Some 227 first SVDs had a much greater fall than 145 subsequent SVDs. In 162 subjects who had undergone their first vaginal delivery and who were followed up there was some recovery but the resting pressures were still lowered at six to 10 weeks post partum. CONCLUSIONS: The first vaginal delivery causes a permanent lowering of resting anal pressures. The possible reasons for this are discussed.

Galileo probe: in situ observations of Jupiter's atmosphere.

The Galileo probe performed the first in situ measurements of the atmosphere of Jupiter on 7 December 1995. The probe returned data until it reached a depth corresponding to an atmospheric pressure of approximately 24 bars. This report presents a brief overview of the origins and purpose of the mission. Science objectives, entry parameters and mission events, and results are described. The remaining reports address in more detail the individual experiments summarized here.

Neural factors influence the degeneration of muscle fibers in the chelae of snapping shrimps.

The asymmetric pincer and snapper claws in the snapping shrimp differ in external morphology and musculature. The snapper is a massive claw used for displays and defense; the pincer is small and slender, used for feeding and burrowing. The snapper has only slow muscle fibers; the pincer has both slow and fast. Removal or denervation of the snapper claw induces transformation of the contralateral pincer to a snapper type of claw at the subsequent molt. A removed claw regenerates as a pincer type, as long as the innervation of the remaining claw is intact. Fast muscle fibers, found exclusively in the pincer claw, normally degenerate completely within 10 d after the moult, which transforms the pincer to a snapper. Morphological transformation of the pincer following removal of the snapper claw can occur even if the pincer claw is denervated. Denervation of the pincer, however, delays degeneration of the fast fibers, increasing the estimated half-time of muscle degeneration, for 4.4 +/- 0.2 to 19.5 +/- 0.8. d after the transforming moult. Neural influences therefore are involved both in the determination of the morphology of the claw and in the induction of degenerative changes during the remodeling of an existing claw.

Electrophysiological assessment of brain function in severe malnutrition.

Brain function in 10 severely malnourished children and matched controls was assessed using spectral analysis of electroencephalographic responses to photic driving during slow-wave sleep. The percentage power in the classical EEG broad-band domains was derived from temporo-occipital records. The malnourished group (5-23 months old; z-score height-for-age -3.2 +/- 0.3, weight-for-height -2.5 +/- 0.3) were tested on admission and on discharge from hospital. No significant differences were found between admission and discharge. Significant differences were found between malnourished and control groups, in the alpha 1 band in the undriven EEG, and in the alpha/beta 1 power ratio while driving at 8 Hz. These electrophysiological abnormalities, persisting despite somatic rehabilitation, must be associated with the chronic rather than the acute aspects of malnutrition, and can index the deviation of brain function from normality.

Bioelectrical-impedance analysis as a measure of body composition in a West Indian population.

Percent body fat (%BF) was estimated in 50 males and 50 females aged 8-21 y by using hydrodensitometry (%BFd) and a bioelectrical-impedance analyzer (%BF-BIA). The sample population was racially heterogeneous, though predominantly of African origin. Percent body fat was computed from density by using an equation derived specifically for blacks. The BIA predicted %BF with r2 = 0.77 (SEE = 3.7%BF), underestimating by a mean of 1.7%BF. Residuals (%BFd - %BF-BIA) were normally distributed but were significantly correlated with age (P less than 0.01), although this effect was small. The theoretical bases for impedance analysis and for hydrodensitometry would appear for different reasons to impair applicability of these techniques to the present population and age group. However, for our population sample the BIA estimated %BF as precisely as other simple techniques applied to other populations.

Antithyroid drugs in the treatment of hyperthyroidism of Graves' disease: long-term follow-up of 434 patients. Scottish Automated Follow-Up Register Group.

A study of antithyroid drug (ATD) therapy with a mean follow-up period of 10 years (range 2-25) in 434 patients with Graves' disease has been made by linking hospital records with those of a central follow-up register. The majority (89%) were treated with carbimazole and 87% received combined therapy with triiodothyronine (T3) (73%) or thyroxine (T4) (14%). Sixty-one per cent were assessed for T3 suppression tests on completion of treatment, of whom 61% (95% CL, 55-67%) suppressed. The overall 5-year cumulative proportion developing recurrent hyperthyroidism was 54-62% with rates of 26-44% in suppressed patients and 65-79% in those not suppressed. In unsuppressed patients, most (72%) of the recurrences occurred within 1 year with only an additional 10% predicted up to 10 years. In suppressed patients 30% of recurrences occurred in the first year, 60% between 1 and 5 years and a further 10% between 5 and 10 years. Suppression with T3 is probably the best and cheapest predictor of outcome but has an accuracy of only 70% for both positive and negative tests which limits its usefulness in planning long-term follow-up and surveillance. A standard format should be adopted for the analysis and reporting of follow-up studies, based on actuarial methods of estimating the cumulative proportion with recurrences or other events, to facilitate comparisons between different centres.

Photoreceptor evoked potentials and phototactic behaviour in Cercaria caribbea LXXI cable.

1. Transient potential changes evoked in response to light stimuli, and presumably arising from rhabdomeric eye-spots in the cercarial body, were recorded for the first time, to our knowledge, in helminth parasites. 2. Pigmented Cercaria caribbea LXXI gave a very slowly adapting response to maintained light stimulus, while a non-pigmented variety appeared to emit a stronger, rapidly adapting response to light onset. 3. Swimming towards a directional light source is disrupted by several neuropharmacological agents, which presumably disturb synaptic transmission in the nerve/muscle system. 4. The light evoked potentials were unaffected by these same agents and therefore, appeared to be directly recorded receptor potentials.

Overview of VEGA Venus Balloon in Situ Meteorological Measurements.

The VEGA balloons made in situ measurements of pressure, temperature, vertical wind velocity, ambient light, frequency of lightning, and cloud particle backscatter. Both balloons encountered highly variable atmospheric conditions, with periods of intense vertical winds occurring sporadically throughout their flights. Downward winds as large as 3.5 meters per second occasionally forced the balloons to descend as much as 2.5 kilometers below their equilibrium float altitudes. Large variations, in pressure, temperature, ambient light level, and cloud particle backscatter (VEGA-1 only) correlated well during these excursions, indicating that these properties were strong functions of altitude in those parts of the middle cloud layer sampled by the balloons.

VEGA Balloon Dynamics and Vertical Winds in the Venus Middle Cloud Region.

The VEGA balloons provided a long-term record of vertical wind fluctuations in a planetary atmosphere other than Earth's. The vertical winds were calculated from the observed displacement of the balloon relative to its equilibrium float altitude. The winds were intermittent; a large burst lasted several hours, and the peak velocity was 3 meters per second.

Thermal structure of the venus atmosphere in the middle cloud layer.

Thermal structure measurements obtained by the two VEGA balloons show the Venus middle cloud layer to be generally adiabatic. Temperatures measured by the two balloons at locations roughly symmetric about the equator differed by about 6.5 kelvins at a given pressure. The VEGA-2 temperatures were about 2.5 kelvins cooler and those of VEGA-1 about 4 kelvins warmer than temperatures measured by the Pioneer Venus Large Probe at these levels. Data taken by the VEGA-2 lander as it passed through the middle cloud agreed with those of the VEGA-2 balloon. Study of individual frames of the balloon data suggests the presence of multiple discrete air masses that are internally adiabatic but lie on slightly different adiabats. These adiabats, for a given balloon, can differ in temperature by as much as 1 kelvin at a given pressure.

Implications of the VEGA Balloon Results for Venus Atmospheric Dynamics.

Both VEGA balloons encountered vertical winds with typical velocities of 1 to 2 meters per second. These values are consistent with those estimated from mixing length theory of thermal convection. However, small-scale temperature fluctuations for each balloon were sometimes larger than predicted. The approximate 6.5-kelvin difference in temperature consistently seen between VEGA-1 and VEGA-2 is probably due to synoptic or planetary-scale nonaxisymmetric disturbances that propagate westward with respect to the planet. There is also evidence from Doppler data for the existence of solar-fixed nonaxisymmetric motions that may be thermal tides. Surface topography may influence atmospheric motions experienced by the VEGA-2 balloon.