Modulatory actions of norepinephrine in the central nervous system.

Early studies have shown that norepinephrine (NE) released synaptically or iontophoretically onto neurons in the central nervous system acts to depress firing by a mechanism associated with a hyperpolarization but no change or an increase in membrane resistance. This in contrast to classical transmitters, which cause hyperpolarization by a conductance increase. Recent studies designed to clarify the functional implications of these biophysical actions have revealed new phenomenons in which the major overall effect of NE on cerebellar Purkinje cells is to enhance conventional synaptic input and induce an increase in signal-to-noise ratio of evoked versus spontaneous activity. NE released iontophoretically or via stimulation of the locus coeruleus also has been found to enhance the inhibitory effects of gamma-aminobutyric acid, an endogenous cerebellar transmitter. The effects appear even at low doses of NE having no direct depressant action on spontaneous activity. Specificity tests have shown no enhancement of glycine-induced inhibition by NE and an inability of dopamine to mimic NE. The hypothesis is presented that a significant action of NE in the central nervous system is to induce a bias that alters postsynaptic responsiveness to conventional transmitter systems, which themselves may be more directly concerned with detailed information transfer.     

Preliminary evaluation of non-native rainbow trout (Oncorhynchus mykiss) impact on the Cederberg ghost frog (Heleophryne depressa) in South Africa’s Cape Fold Ecoregion

We evaluated the impact of non-native rainbow trout Oncorhynchus mykiss on a population of endemic Cedarberg ghost frog Heleophryne depressa in the upper Krom River (Olifants-Doring River Catchment, Cape Fold Ecoregion). We compared H. depressa abundance (using kick-sampling and underwater video analysis) and environmental conditions between sites above and below a waterfall that marks the upper distribution limit of O. mykiss. Heleophryne depressa abundance was significantly greater above the waterfall than that below it, and, because there was no significant difference in measured environmental variables, O. mykiss presence is identified as the most likely explanation for the observed decrease in H. depressa abundance.     

Effect of reducing anatomic dead space on arterial PCO2 during CO2 inhalation

Carotid body-denervated (CBD) ponies have a less than normal increase in arterial PCO2 (PaCO2) when inspired CO2 (PICO2) is increased, even when pulmonary ventilation (VE) and breathing frequency (f) are normal. We studied six tracheostomized ponies to determine whether this change 1) might be due to increased alveolar ventilation (VA) secondary to a reduction in upper airway dead space (VD) or 2) is dependent on an upper airway sensory mechanism. Three normal and three chronic CBD ponies were studied while they were breathing room air and at 14, 28, and 42 Torr PICO2. While the ponies were breathing room air, physiological VD was 483 and 255 ml during nares breathing (NBr) and tracheostomy breathing (TBr), respectively. However, at elevated PICO2, mixed expired PCO2 often exceeded PaCO2; thus we were unable to calculate physiological VD using the Bohr equation. At all PICO2 in normal ponies, PaCO2 was approximately 0.3 Torr greater during NBr than during TBr (P less than 0.05). In CBD ponies this NBr-TBr difference was only evident while breathing room air and at 28 Torr PICO2. At each elevated PICO2 during both NBr and TBr, the increase in PaCO2 above control was always less in CBD ponies than in normal ponies (P less than 0.01). The VE-PaCO2, f-PaCO2, and tidal volume-PaCO2 relationships did not differ between NBr and TBr (P greater than 0.10) nor did they differ between normal and CBD ponies (P greater than 0.10). We conclude that the attenuated increase in PaCO2 during CO2 inhalation after CBD is not due to a relative increase in VA secondary to reducing upper airway VD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gossypol modulation of nucleotide metabolizing enzymes in the reproductive tract of male rats

The activities of several pivotal nucleotide metabolizing enzymes from the testis and vasal sperm of rats treated for 7 wk with 0, 20 or 30 mg X kg X day gossypol acetic acid were examined. Total testicular lactate dehydrogenase (LDH) activity increased 40% above control in the highest treatment group examined. However, the specific activity of the testis-specific isozyme of LDH, LDH-C4, decreased to 50 and 20% of control in the 20 and 30 mg X kg X day treatment groups, respectively. Basal soluble adenylate cyclase from a 100,000 X g supernatant of testis homogenate exhibited a 25% decrease in activity only in the 30-mg treatment group. Basal adenylate cyclase activity in the testicular membrane fraction increased 20 to 30% above control in response to gossypol administration. Testis membranes from the 20- and 30-mg treatment group exhibited a 2- and 4-fold greater activation of adenylate cyclase by guanine nucleotides. In vitro dose-response curves showed a half-maximal inhibitory concentration (IC50) for inhibition of soluble testicular adenylate cyclase by gossypol of 400 microM in each treatment group. Caudal epididymal sperm adenylate cyclase activity decreased to 25% of control levels in gossypol-treated animals, and the in vitro sensitivity of the enzyme to the inhibitory effects of gossypol increased 4-fold. IC50 values for gossypol inhibition of sperm adenylate cyclase decreased from 200 microM in control animals to 75 and 50 microM in the 20 and 30 mg X kg X day treatment groups, respectively. Cyclic adenosine 3':5' monophosphate phosphodiesterase activity in caudal sperm increased 6-fold in the 20- and 30-mg treatment groups. These results demonstrate that nucleotide metabolizing enzymes in sperm are major targets for the actions of gossypol and provide a possible mechanism for the inhibition of normal sperm function by this compound.     

Metal contamination and human health risk associated with the consumption of Labeo rosae from the Olifants River system,South Africa

The Olifants River, a tributary of the Limpopo River system, is one of the most polluted rivers in South Africa. In May 2011 the concentrations of metals in fish muscle tissue from two impoundments, Loskop and Flag Boshielo dams, on the Olifants River were measured and a human health risk assessment conducted to investigate whether it was safe to consume Labeo rosae from these impoundments. Labeo rosae is one of the most common pan fish in these impoundments and is readily available to rural communities. Metals are accumulating in the muscle tissue of L. rosae even although the fish populations appear to be healthy. At Loskop Dam all L. rosae analysed exceeded the recommended hazard quotient (HQ) of 1 for antimony, and less than 50% exceeded that for lead. At Flag Boshielo Dam, the recommended HQ was exceeded for lead in less than 50% of L. rosae analysed, and more than 50% exceeded that for antimony. The weekly consumption of 150?g of L. rosae muscle tissue from these impoundments may pose an unacceptable health risk to rural communities.     

Electrophysiological effects of enkephalin analogs in rat cortex.

The microiontophoretic potencies of methionine-enkephalin (ME) analogs with similar charges but different potencies in the $\text{in vitro}$ assays were studied with respect to spontaneous and evoked activity of rat cerebral cortex neurons (CX). ME slowed discharge in 65% of the 62 CX tested; activity evoked by acetylcholine (ACh) or glutamate, as well as spontaneous discharge, was affected. The vast majority of responsive cells were deeper than 500 μ and excited by ACh. Antidromic spikes were elicited in many of these neurons by pyramidal tract stimulation. The electrophysiological effects of D-Ala² ME amide, a more potent analog $\text{in vitro}$, was similar to ME when tested on the same parietal CX, however, D-Ala² ME amide was much more potent than ME on frontal CX. On the other hand N-acetyl D-Ala²-Lys³ ME amide, which has low potency $\text{in vitro}$, had little effect on CX which were readily depressed by equivalent doses of ME or the D-Ala² analog. The depressions induced by ME or the D-Ala² derivative were readily and reversibly antagonized by prior iontophoretic administration of naloxone. It is concluded that opiate receptor interactions may play an important role in electrophysiological responses to iontophoretically administered ME and that the deeper cholineceptive cortical cells, possibly pyramidal neurons, may be preferentially affected.     

The electronic medical-student exchange: a low-cost alternative to overseas electives.

The authors report on an international collaboration that uses the Internet for medical education. In addition to introducing the students to electronic communication, the project aims to further international collaboration and understanding and to emphasize the importance of a population perspective for health and disease. Students and professors in Canada, England and Hungary participated.