The effect of urinary pH and flow rate on monoamine output.

Three-hour urinary output values of dopamine, noradrenaline, adrenaline, 2-phenylethylamine and p-tyramine were measured in normal volunteers who had been induced, by pretreatment with ammonium chloride or sodium bicarbonate, to excrete maximally acid or alkaline urine. There were significant effects on the excretion of dopamine, adrenaline and 2-phenylethylamine, inversely proportional to urinary pH value. Adrenaline output increased with increasing urinary flow rate. There was a significant correlation between urinary concentrations of 2-phenylethylamine and p-tyramine. These findings may have important clinical implications.     

Potassium induced release of GABA and other substances from the guinea pig cochlea

Gamma-aminobutyric acid (GABA) has been proposed as a neurotransmitter of a subset of efferent nerve fibers in the mammalian cochlea. We tested this hypothesis by examining if GABA was released by high concentrations of K+ from the guinea pig cochlea. Artificial perilymph solutions containing either normal K+ (5 mM) or high K+ (50 mM) were perfused through the perilymphatic compartment of the guinea pig cochlea while collecting the effluent. Nineteen primary amines including GABA were quantified in the effluent by HPLC. This was carried out in normal animals and in animals pretreated with ethacrynic acid and kanamycin to destroy the organ of Corti. Significantly greater levels of GABA, taurine, glutamate, aspartate, glycine and three unidentified substances appeared in effluent collected during exposure of the cochlea to solutions containing higher K+ than normal K+. Compared to normal animals, destruction of the organ of Corti significantly decreased the K(+)-induced release of GABA, taurine, glutamate, aspartate, glycine and one of the unidentified substances; although significant release of glutamate and taurine still occurred in the destroyed ears. The release of GABA is consistent with it being a neurotransmitter in the cochlea. In addition the results: confirm the release of glutamate and taurine from the organ of Corti; suggest that additional substances may be released; and demonstrate the release of glutamate and taurine from tissue other than the organ of Corti.     

Kynurenic acid and gamma-D-glutamylaminomethylsulfonic acid suppress the compound action potential of the auditory nerve

Kynurenic acid and gamma-D-glutamylaminomethylsulfonic acid, two excitatory amino acid antagonists, were perfused through the guinea pig cochlea while monitoring various cochlear potentials. Both drugs (0.6-10 mM) reduced the magnitude of the compound action potential (CAP) of the cochlear nerve without much effect on other potentials. The results are consistent with the hypothesis that the hair cell transmitter is an excitatory amino acid, possibly L-glutamate.     

In vitro killing of community-associated methicillin-resistant Staphylococcus aureus with drug combinations

This study employs time-kill techniques to examine the most common drug combinations used in the therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin plus either gentamicin or rifampin. Community-associated MRSA were more likely to be synergistically inhibited by combinations of vancomycin and gentamicin versus vancomycin alone compared to inhibition associated with hospital-acquired strains.     

Changing cation levels (Mg2+, Ca2+, Na+) alters the release of glutamate, GABA and other substances from the guinea pig cochlea.

We examined the effects of changes in cation levels (increased Mg2+ concentration combined with low Ca2+ concentration, and two low concentrations of Na+) on the perilymph levels of gamma-aminobutyric acid (GABA), glutamate (Glu), aspartate (Asp) and other substances. Artificial perilymph solutions containing normal (5 mM) and high (50 mM) levels of K+ were perfused through the perilymphatic compartment of the guinea pig cochlea to examine basal release (5 mM K+) and depolarization-induced release (50 mM K+). Each of the two K+ concentrations were contained in four different solutions: [I] normal artificial perilymph (NARP; NaCl, 137 mM; CaCl2, 2 mM; MgCl2, 1 mM;); [II] high Mg2+ (20 mM)/low Ca2+ (0.1 mM) (HMgLCa); [III] low Na+ (117 mM; LNa), and [IV] very low Na+ (NaCl, 0 mM; VLNa). The effluent was collected and assayed for eighteen primary amines by HPLC. Compared with NARP, the HMgLCa group had an increase in the high K(+)-induced release of Asp and Glu with no change in GABA. VLNa increased the normal K+ levels of Asp, Glu and GABA up to those observed with high K+ in NARP. VLNa increased the high K+ levels of Asp and Glu over fivefold compared with the high K+ levels in NARP, but decreased GABA. We ascribe the results to an interference with either a Na(+)-dependent uptake processes or a Na+/Ca2+ exchange carrier.     

Academic and cognitive abilities in children of parents with bipolar disorder: a test of the nonverbal learning disability model

It has been hypothesized that children who are at genetic risk to develop bipolar disorder demonstrate deficiencies consistent with the syndrome of nonverbal learning disabilities (NLD); however, this hypothesis has never been tested directly. In the present study, a group of at-risk children (AR group; N = 28) was compared to a demographically matched control group of children of healthy parents (HC group; N = 24) for evidence of a constellation of features associated with NLD. Some characteristic features of NLD were evident, including significant Verbal IQ (VIQ) > Performance IQ (PIQ) discrepancies and psychomotor deficits. However, academic deficiencies in mechanical arithmetic relative to reading and spelling abilities were not demonstrated. These findings replicate and extend the current literature on the cognitive functioning of children of parents with Bipolar disorder (BPD). The results, however, do not support the presence of NLD in these children.     

Administration of protein-conjugate pneumococcal vaccine to patients who have invasive disease after splenectomy despite their having received 23-valent pneumococcal polysaccharide vaccine

Patients who undergo splenectomy are at greatly increased risk for overwhelming pneumococcal bacteremia and death. Twenty-three-valent pneumococcal polysaccharide vaccine (PPV-23), which contains capsular polysaccharides (PSs) from 23 common serotypes of Streptococcus pneumoniae, is strongly recommended for such patients. The capacity to respond to PPV-23 by producing immunoglobulin (Ig) G is genetically regulated. Some proportion of adults do not respond and, despite postsplenectomy administration of PPV-23, may remain susceptible to recurrent pneumococcal sepsis. Here, we describe 2 patients who had recurring pneumococcal bacteremia after undergoing splenectomy despite having received numerous doses of PPV-23. Heptavalent protein-conjugate pneumococcal vaccine (PCPV-7) was then administered, and it induced high levels of IgG to all 7 PSs; in one of the patients, functional activity against 5 of the 7 PSs was demonstrable, both in vitro and in vivo. Recurrent pneumococcal bacteremia in patients who have undergone splenectomy may indicate a genetically regulated failure to respond to PPV-23; PCPV-7 may stimulate production of IgG to PSs in such patients.