Relation of serum albumin concentration to death rate in nursing home men

Serum albumin was measured in 126 men (average age 70.6; range 40 to 96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base, including death or survival during the year after the analysis. The reason for institutionalization was chronic neurologic disease or other disabling physical condition in 63 men (group A), and psychiatric disorder in 63 men (group B). In group A, the proportions of men with albumin less than 3.5, 3.5-4.0, and greater than 4.0 g/dl were 6%, 37%, and 57%, respectively. In this group, the serum albumin level was significantly (p less than 0.05) correlated with death rate, hemoglobin, hematocrit, serum cholesterol, and serum lactic dehydrogenase. The death rate in group A during the year after the albumin analysis was 25%. For the patients with albumin level less than 3.5, 3.5-4.0, and greater than 4.0 g/dl, the death rates were 50%, 43%, and 11% respectively (p less than 0.01 for comparison of the former two groups with the latter). The subgroup with albumin 3.5-4.0 g/dl represented only 37% of the men in group A, but accounted for 63% of the group's deaths. In group B, serum albumin level was not significantly correlated with any other clinical variable. Death rate during the year after the albumin analysis was only 2% in group B, and did not correlate with the albumin level. These data indicate that, in nonpsychiatric Nursing Home men, the desirable level for the serum albumin concentration is higher than 3.5 g/dl.     

Synthesis, phencyclidine-like pharmacology, and antiischemic potential of meta-substituted 1-(1-phenylcyclohexyl)-1,2,3,6-tetrahydropyridines

A series of 1-[1-arylcyclohexyl]-1,2,3,6-tetrahydropyridines were prepared by the reaction between 1-(1-cyanocyclohexyl)-1,2,3,6-tetrahydropyridine (1) and an appropriately substituted Grignard reagent. The resulting compounds were tested for their phencyclidine binding site affinities. Selected compounds were then tested for their ability to produce ketamine appropriate responding in monkeys and/or to show neuroprotective effects in a baby rat hypoxia/ischemia model. While it was found that binding site affinity correlated well with discriminative stimulus effects, it was found to be a poor indicator of neuroprotective efficacy within this series.     

Prognostic significance of serum cholesterol in nursing home men

Serum cholesterol was measured in 129 men (average age 70.6; range 41-96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base. Serum cholesterol was less than 150 mg/dl in 13% of the subjects, and was less than 160 mg/dl in 18%. Cholesterol greater than 280 mg/dl occurred in 8%. Serum cholesterol varied directly (p less than 0.02) with: body weight, serum albumin, serum total protein, serum sodium, ability to walk, and ability to feed oneself; and indirectly (p less than 0.02) with death rate, degree of functional dependence, and serum SGOT and LDH. Nursing home men with cholesterol less than 150 mg/dl had a death rate of 63% during the 14 months after the cholesterol analysis, compared to a death rate of 9% in men with cholesterol greater than 150 mg/dl (p less than 0.05). Death rate during the year after the analysis was 52% if cholesterol was below 160 mg/dl, compared to 7% if it was above this threshold (p less than 0.05).     

ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

Activities in cellular signalling pathways: a two-edged sword?

The maintenance and adaptive plasticity of neural circuitry requires the coordinated activities of an array of signal transduction systems. These different signalling systems play critical roles in carving out and modifying functional neural circuitry in development and adult plasticity. Ironically, aberrant activity in these systems may sever neural connections and take the lives of neurons in a variety of disorders including Alzheimer's disease. A rather complex set of circumstances must be taken into account when considering the consequences of activity in pathways that regulate neuroarchitecture. The specific signalling pathways activated, their levels of activation, activity in other pathways, and environmental conditions are among the factors that enter into the equation for determining whether use is a boon or a bane.     

Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons

The present study examined the effects of glutamate on the outgrowth of dendrites and axons in isolated hippocampal pyramidal-like neurons in cell culture. During the first day of culture the survival and outgrowth of these neurons was unaffected by high concentrations (up to 1 nM) of glutamate, quisqualic acid (QA), kainic acid (KA), and N-methyl-D-aspartic acid. Beginning on day 2 of culture high levels of glutamate, KA and QA were toxic to the majority of pyramidal neurons, while subtoxic levels of these agents caused a well-defined, dose-dependent, sequence of effects on dendritic outgrowth. At increasing concentrations of glutamate, QA, and KA, the following events were observed: (1) dendritic outgrowth rates were reduced, while axonal elongation rates were unaffected; (2) dendritic length was reduced, while axons continued to grow; (3) dendrites regressed dramatically, and axonal outgrowth rate was reduced. These dendrite-specific effects of glutamate were apparently mediated at the growth cones since focal application of glutamate to individual dendritic growth cones resulted in suppression of growth cone activity and a regression of the dendrite; axons were unaffected by focal glutamate application. Pharmacological tests using glutamate receptor agonists and antagonists demonstrated that receptors of the KA/QA type mediated the glutamate effects on outgrowth and survival. The calcium channel blocker Co2+ prevented both glutamate neurotoxicity and glutamate-induced dendritic regression. Ionophore A23187 and elevations in extracellular K+ levels each caused a dose-dependent series of outgrowth and survival responses similar to those caused by glutamate. Taken together, these results indicate that activation of glutamate receptors leads to the opening of voltage-dependent calcium channels; the resulting increases in calcium influx lead to the observed alterations in dendritic outgrowth and neuronal survival.