Lipid-based nutrient supplements containing vitamins and minerals attenuate renal electrolyte loss in HIV/AIDS patients starting antiretroviral therapy: A randomized controlled trial in Zambia.

BACKGROUND & AIMS: Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. METHODS: 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. RESULTS: Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups. CONCLUSIONS: The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings. TRIAL REGISTRATION: www.pactr.org ID number: PACTR201106000300631.

Inhaled benzo(a)pyrene impairs long-term potentiation in the F1 generation rat dentate gyrus.

The purpose of this study is to provide a point of reference regarding the neurotoxic effects resulting from exposure to environmental contaminants. Benzo(a)pyrene is a member of the polycyclic aromatic hydrocarbon (PAH) family and it is a by-product of combustion processes. Thus, persons living near factories or hazardous waste sites face the danger of exposure through contact with contaminated air, water and soil. In an effort to understand the impact of environmental contaminants, we have investigated the effects of gestational B(a)P aerosol exposure on long-term potentiation (LTP), a cellular correlate of learning and memory in the F1 generation. Briefly, timed-pregnant rats were exposed to B(a)P via nose-only inhalation on gestation days 11-21 for 4 hr per day. Dams were maintained to term and pups were weaned on postnatal day 30. Subsequent electrophysiological studies during postnatal days 60-70 revealed a diminution in LTP across the perforant path-granular cells synapses in the hippocampus of F1 generation animals that were transplacentally exposed to B(a)P aerosol relative to unexposed controls. Additionally, NMDA receptor subunit 1 (NR1) protein was found to be downregulated in the hippocampus of B(a)P exposed F1 generation animals. Taken together, our results suggest that gestational exposure to B(a)P aerosol attenuates the capacity for LTP in the F1 generation.

An in vivo model for investigating bilateral synaptic plasticity across CA3/CA1 synapses in guinea pig dorsal hippocampus.

A method is described for concurrent investigation of long-term potentiation (LTP) in the left and right CA1 synapses in dorsal hippocampi in guinea pig in vivo. Briefly, animals are anesthetized with urethane, and small access holes are made in the skull through which electrodes are lowered to stimulate the left CA3 and record from both CA1 regions. Using this animal model, we have found that LTP is produced in both CA1 regions, following conditioning stimulation to the left CA3. However, in some animals LTP occurred in the left CA1 without concomitant synaptic potentiation in the contralateral CA1. We also observed that in some experiments synaptic potentiation in the contralateral CA1, when present, decayed to baseline levels even though LTP persisted in the ipsilateral CA1. To conclude, our data on bilateral LTP demonstrates findings that are best addressed in vivo.

Age-dependent changes in cat masseter nerve: an electrophysiological and morphological study.

The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study.

Blockade of hippocampal long-term potentiation by saccharin.

Population spikes, population excitatory postsynaptic potentials and intracellular excitatory postsynaptic potentials were recorded in the CA1 area of guinea-pig hippocampal slices in response to low frequency stimulation of the stratum radiatum. Tetanic stimulation of the same afferents during an application of saccharin (10 mM, 10 min) failed to induced a long-term potentiation of the population spike, population excitatory postsynaptic potential and intracellularly recorded excitatory postsynaptic potential. A post-tetanic application of saccharin did not prevent long-term potentiation of the population spike from developing. Saccharin did not change the input resistance, the membrane potential or the ability to induce action potentials in the CA1 neurons. The slope of the intracellular excitatory postsynaptic potentials recorded in normal medium, in normal medium containing 2-amino-5-phosphonovalerate, or in Mg(2+)-free medium containing 6-cyano-7-nitroquinoxaline-2,3-dione was not significantly altered by saccharin. The depolarizations of CAI neurons produced by superfusion of N-methyl-D-aspartate or during a brief tetanic stimulation of the stratum radiation were also not altered by the drug. It therefore appears that saccharin blocks the induction of long-term potentiation by a mechanism that does not involve a blockade of N-methyl-D-aspartate receptors. Application of fluid samples collected from rabbit neocortical surface during a tetanic stimulation of the neocortex caused neurite growth in PC-12 cells, suggesting that growth-related substances were present in the collected samples. If these samples were superfused onto hippocampal slices, long-term potentiation developed. If however, the samples were co-applied with saccharin, neither neurite growth in PC-12 cells nor long-term potentiation in hippocampal slices was observed, raising the possibility that growth-related substances are involved in long-term potentiation.

Strychnine antagonizes jaw-closer motoneuron IPSPs induced by reticular stimulation during active sleep.

In chronic, unanesthetized, normally respiring cats, stimulation of the nucleus reticularis pontis oralis induced inhibitory postsynaptic potentials (IPSPs) in masseter motoneurons during active sleep, but not during wakefulness or quiet sleep. Strychnine, when applied juxtacellularly by microiontophoresis to masseter motoneurons, specifically suppressed the active sleep-dependent IPSPs. In contrast, bicuculline did not suppress the active sleep-dependent IPSPs. These results indicate these IPSPs are mediated by the putative neurotransmitter glycine.

Intraarticular bupivacaine (Marcaine) after arthroscopic meniscectomy: a randomized double-blind controlled study.

In this study, 79 patients undergoing arthroscopic meniscectomy were entered into a randomized double-blind controlled trial in which intraarticular bupivacaine (Marcaine), was compared with a saline placebo. Intraarticular bupivacaine was shown to be an effective and safe method of achieving analgesia after arthroscopic meniscectomy.

Substances released during tetanic stimulation of rabbit neocortex induce neurite growth in PC-12 cells and long-term potentiation in guinea pig hippocampus.

Samples collected from rabbit neocortical surface during a tetanic stimulation of the neocortex induced neurite growth in PC-12 cells in culture and synaptic long-term potentiation (LTP) in guinea pig hippocampal slices. If these samples were preheated and cooled, or if they were collected in the absence of a tetanic stimulation of the rabbit neocrotex, they did not induce neurite growth in PC-12 cells or LTP in the guinea pig hippocampus. These results suggest that neurite-inducing factors are released during tetanic stimulations and that these substances are involved in LTP.

Asynchronous synaptic responses in hippocampal CA1 neurons during synaptic long-term potentiation.

In guinea pig hippocampal slices incubated in Ba2+, stimulation of stratum radiatum induced an EPSP that was followed by an increased frequency of miniature EPSPs in CA1 neurons. These miniature EPSPS, which were presumably due to the asynchronous release of transmitter, were increased after the induction of long-term potentiation.

The involvement of nonspiking cells in long-term potentiation of synaptic transmission in the hippocampus.

In guinea pig hippocampal slices, stimulation of stratum radiatum during depolarization (with intracellular current injections) of nonspiking cells (presumed to be glia) in the apical dendritic area of CA1 pyramidal neurons resulted in a subsequent long-term potential of intracellularly recorded excitatory postsynaptic potentials as well as extracellularly recorded population spikes in the CA1 area. Tetanic stimulation of stratum radiatum resulted in a subsequent prolonged depolarization of the presumed glial cells, and this depolarization was smaller when the tetanus was given during the presence of 2-amino-5-phosphonovalerate or when the slices were exposed to Ca2+-free medium containing Mn2+ and Mg2+. These results suggest that glial depolarization is involved as one of the steps in generating long-term potentiation.

Effect of a volatile anesthetic upon presynaptic excitability in mammalian hippocampus.

Changes in presynaptic terminal axon excitability produced by enflurane in the rat hippocampal slice preparation were investigated by stimulation of Schaeffer collateral terminal axons and by recording single unit antidromic action potentials. Stimulating pulses were preceded by conditioning hyperpolarizing or depolarizing current pulses. A plot of net threshold for action potential generation against the conditioning pulse yields an "accommodation curve;" changes in this curve can be used to assess the mechanism by which changes in excitability are produced. Enflurane, at a concentration equivalent to approximately equal to 1.3 times the minimum alveolar concentration, reduced excitability of terminal axons and increased accommodation in a manner consistent with a possible change in the inactivation of gNa.

Verapamil counteracts depression but not long-lasting potentiation of the hippocampal population spike.

In transversely sectioned rat hippocampal slices, population spikes and population "EPSPs" were recorded from CA1 neurones in response to the stimulation of Schaffer collateral and commissural inputs. High frequency tetanic stimulation (400 Hz, 200 pulses) of an input induced LLP of the homosynaptic response without significantly changing the heterosynaptic response. This LLP was not interrupted by either a 400 Hz tetanus given to the heterosynaptic input or by verapamil (0.33 microM) which blocks Ca++ channels, but not transmitter release. A low frequency tetanus (20 Hz, 200 pulses) given to an input induces co-occurring homosynaptic and heterosynaptic depressions of about 20 min duration. This tetanus could also mask an established LLP in homosynaptic or heterosynaptic pathway. Verapamil counteracts homo- and heterosynaptic depressions. The population spike as well as the population "EPSP" were depressed following iontophoretic application of Ca++ (2-100 nA) at the CA1 cell body area. These results indicate that homosynaptic and heterosynaptic depressions are at least partly due to an accumulation of Ca++ into CA1 neurones. An established LLP is not interrupted by LLP of another input. Homo- and heterosynaptic depressions mask, but not reverse, LLP.