How in the world is WHO doing?

The World Health Organization has chalked up some impressive victories in its 43 years but is nowhere near reaching its ambitious goal of "Health for All by the Year 2000." Uphill battles against some intractable health conundrums and shrinking financial resources face the Geneva, Switzerland-based organization, threatening its stated goal of guaranteeing universal health care within the decade.     

Synergistic Regulation of Cytosolic Ca2+ Concentration by Adenosine and alpha1-Adrenergic Agonists in Mouse Striatal Astrocytes

Adenosine has a broad array of actions on neurons but astrocytes also possess adenosine receptors. We have previously shown that adenosine, by acting on astrocytes in the striatum, can modulate neuronal responses mediated by receptors coupled to phospholipase C through an astrocyto - neuronal interaction. In addition, adenosine was found to potentiate the alpha1-adrenergic production of inositol phosphates in astrocytes. The mechanism involved in this potentiation was further investigated by examining the effects of adenosine and alpha1-adrenergic receptor agonists on cytosolic Ca2+ in cultured striatal astrocytes from the embryonic mouse in primary culture. When used alone, methoxamine, a selective agonist of alpha-adrenergic receptors or 2-chloroadenosine, a stable analogue of adenosine, induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+, which seems to be due to a Ca2+ influx, because it was not observed in the absence of external Ca2+. Voltage independent Ca2+ channels contribute to this process and different blockers of voltage-operated calcium channels, such as dihydropyridines, phenylalkylamines, La3+ or Co2+ were ineffective in suppressing the sustained cytosolic Ca2+ elevation. Three observations suggest the implication of arachidonic acid in the observed potentiation: (i) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the coapplication of methoxamine and 2-chloroadenosine; (ii) the addition of arachidonic acid during the calcic plateau produced by the combined application of the agonists did not increase further cytosolic Ca2+ levels; (iii) in the presence of methoxamine, 2-chloroadenosine induced a release of arachidonic acid. The stimulation of phospholipase C and the resulting activation of protein kinase C induced by methoxamine seem to be required for the potentiating effect of 2-chloroadenosine on cytosolic Ca2+. In fact, the direct activation of protein kinase C by an exogenous diacylglycerol analogue mimicked the effect of methoxamine because, in this condition, 2-chloroadenosine alone evoked a sustained elevation of cytosolic Ca2+. Therefore, methoxamine, through the successive activation of phospholipase C and protein kinase C, could allow a lipase, probably phospholipase A2, to be stimulated by 2-chloroadenosine. Arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates in other cell types. Therefore, in striatal astrocytes, 2-chloroadenosine, through an arachidonic acid-mediated hyperpolarization, could increase the Ca2+ driving force and thus improve Ca2+ influx through inositol phosphate-gated channels. This hypothesis is further supported by the suppressing effect of a 50 mM KCI-induced depolarization on the long lasting elevation of cytosolic Ca2+ seen in the combined presence of 2-chloroadenosine and methoxamine.     

The cardiovascular and metabolic effects of bench stepping exercise in females.

The purpose of this investigation was to measure cardiovascular and metabolic responses to 20 min continuous bouts of "choreographed" bench stepping exercise in healthy females. Four frequently used bench heights were employed in a cross-over design: 15.2 cm (6 inches, B-6), 20.3 cm (8 inches, B-8), 25.4 cm (10 inches, B-10), and 30.5 cm (12 inches, B-12). Oxygen uptake (VO2) responses were significantly more pronounced in direct relationship to the bench height: B-12 greater than B-10 greater than B-8 greater than B-6 (P less than 0.05). Mean responses for VO2 ranged from 28.4 ml.kg-1.min-1 for B-6 to 37.3 ml.kg-1.min-1 for B-12. Interestingly, no difference was revealed for heart rate and the respiratory exchange ratio between B-12 and B-10 despite a higher VO2 for B-12 (B-12, B-10 greater than B-8 greater than B-6, P less than 0.05). The incorporation of 0.91 kg (2 lb) hand weights with exercise on the 20.3 cm bench elicited a modest but statistically significant increase in VO2 compared with no hand weights. No significant increase in VO2 was revealed for conditions that employed 0.45 kg (1 lb) hand weights. The results demonstrate that aerobic bench stepping is an exercise modality that provides sufficient cardiorespiratory demand for enhancing aerobic fitness and promoting weight loss in females.     

A review of computerized tomography evaluation of acetabular fractures--part 1

Computerized tomography is an established modality for use in the evaluation of acetabular fractures. As open reduction and internal fixation of acetabular fractures becomes more common, the need for an accurate understanding of the fracture anatomy is critical. An anatomic study of the innominate bone is reported and the relevant standard radiographic landmarks as seen with computerized tomography are illustrated.     

Intracerebral venous angiomas as a cause of exophthalmos.

Three cases of an infrequent cerebral vascular malformation, venous angioma, are reported. The first 2 of these cases, with the lesion in a supratentorial location, exhibited exophthalmos as a presenting symptom, together with palpebral or intraobital angiomatous formations, and also impairment of visual function. The first patient was operated upon and the "venous angioma" could be confirmed histologically. An angiographic follow-up of the same patient at an 18 year interval was also possible. The diagnostic work-up to be performed in cases of exophthalmos is discussed and the need for angiography is stressed.     

Single-dose tolerance to the behavioral effects of dibutyryl cyclic AMP in mice

The behavioral effects of varying doses of intraperitoneally administered dibutyryl cyclic AMP, cyclic AMP, adenosine, 5-AMP, and butyric acid were studied in male ICR mice. Behavioral parameters 25 min following treatment included measurement of spontaneous locomotor activity (SLMA) and rotarod performance, the latter providing an indication of neuromuscular coordination. Dibutyryl cyclic AMP produced a dose-related inhibition of SLMA with the largest dose, 75 mg/kg, decreasing activity by 89%. Adenosine and 5-AMP produced maximal inhibition of approximately 50–80% of SLMA at doses ranging from 75–250 mg/kg, while cyclic AMP decreased SLMA by 58% at only the highest dose, 250 mg/kg. Butyric acid failed to produce alterations in SLMA at doses ranging from 25–250 mg/kg. No compound altered neuromuscular coordination. Single-dose tolerance to the inhibitory effect of dibutyryl cyclic AMP on SLMA developed within 3 h and lasted at least 7 days. Adenosine failed to produce tolerance while cyclic AMP and 5-AMP exhibited only a slightly reduced effect following a second injection at intervals of 4 and 24 h. These results suggest that exogenous administration of dibutyryl cyclic AMP and its metabolites exert centrally mediated behavioral effects with selective development of single-dose tolerance to the dibutyryl derivative.     

Gender differences in supported employment

Questions about gender equity have been asked in many aspects of the disability field and have resulted in findings that women with disabilities have significantly different experiences than do men. We analyzed an existing database of information on supported employment and natural supports to ascertain whether gender plays an important role in the employment of people with mental retardation. The findings suggest that there are several important differences. Although women were perceived as being more socially appropriate on several dimensions, they worked in jobs traditionally stereotyped by gender. Women also typically worked fewer hours than did men and, therefore, earned less money, although not statistically significantly so. The pattern of findings suggests parallels with the broader society.     

Spatiotemporal profile of synaptic activation produced by the electrical and visual stimulation of retinal inputs to the optic tectum: a current source density analysis in the pigeon (Columba livia)

The optic tectum of the pigeon is a highly organized, multilayered structure that receives a massive polystratified afference of at least five different populations of retinal ganglion cells and gives rise to various anatomically segregated efferent systems. The synaptic organization of retino-tectal circuitry is, at present, mostly unknown. To investigate the spatiotemporal profile of synaptic activation produced by differential (electrical and visual) stimulation of the retinal inputs, we performed a high-spatial-resolution current source density analysis in the optic tectum of the anaesthetized pigeon. Electrical stimuli consisted of brief pulses of different durations applied to the optic nerve head, while visual stimuli consisted of light flashes of different intensities. Electrical stimulation generated sinks confined to retinorecipient layers. The temporal structure, spatial location and thresholds of these sinks indicated that they are all due to primary tectal synapses of retinal fibers with different conduction velocities. Sinks evoked by the fastest retinal axons were more superficially located than sinks produced by slower retinal fibers. Visual stimulation, on the other hand, resulted in a more complex pattern of current sinks, with various sinks located in the retinorecipient layers and also well below. Visual stimulation induced action potentials at superficial as well as deep tectal levels. We conclude that electrical stimulation activates most of the populations of ganglion cells as well as their primary tectal synapses, but is unable to elicit a significant activation of secondary tectal synapses. Visual stimulation, on the contrary, activates just some of the incoming retinal populations, but in a way that produces noticeable secondary activation of intratectal circuits. Laminar segregation of retinally evoked tectal activity, as reported here, has also been found in other vertebrates. Similarities and differences with previous studies are discussed.     

Running and cocaine both upregulate dynorphin mRNA in medial caudate putamen

Physical activities such as long-distance running can be habit forming and associated with a sense of well-being to a degree that justifies comparison with drug-induced addictive behaviours. To understand molecular similarities and dissimilarities controlling these behaviours in humans we compared the effects of running in running wheels to the effects of chronic cocaine or morphine administration on mRNA levels in brain reward pathways in the inbred Fischer and Lewis rat strains. These strains are both inbred from the Sprague-Dawley strain; Lewis rats display a higher preference towards addictive drugs and running than do Fischer rats. After chronic cocaine or running a similar increase of dynorphin mRNA in medial caudate putamen was found in the Lewis rat, suggesting common neuronal adaptations in this brain region to both cocaine and running. Fischer and Lewis rats both responded to cocaine with increased dynorphin mRNA levels in medial caudate putamen. However, only Lewis rats increased dynorphin mRNA after running, possibly reflecting the much higher degree of running by the Lewis strain as compared to the Fischer strain. Moreover, the running-induced upregulation of dynorphin mRNA was blocked by the opioid receptor antagonist naloxone. We suggest that running increases dynorphin mRNA by a mechanism that involves endogenous opioids. The voluntary wheel-running model in rats might be used to study natural reward and compulsive behaviours and possibly also to screen candidate drugs for treatment of compulsive disorders.