Adult rat olfactory nerve ensheathing cells are effective promoters of adult central nervous system neurite outgrowth in coculture

A coculture method is described for ensheathing glial cells from adult rat olfactory nerve, serving as a substrate for the regrowth of neurites from adult rat retinal ganglion cells. Immunocytochemically identified phenotypes present in primary cultures of olfactory nerve cells are described, and their ability to promote neurite outgrowth is compared with neonatal astrocytes and Schwann cells, with other nonglial cells, and with laminin. Ensheathing cell cultures were more effective than any other substrate tested and also directed the orientation of regrowing neurites. In comparison with cultured Schwann cells, which released neurotrophic factors into the culture medium, there was no evidence of a similar activity in ensheathing cell cultures. Combinations of ensheathing cell-conditioned medium and substrates of laminin, merosin, or 3T3 cells also failed to show the release of factors enhancing either survival or neurite outgrowth from retinal ganglion cells. Evidence is presented for a partial inhibition of neurite outgrowth in the presence of calcium channel antagonists or an intracellular calcium-chelating reagent. This provides evidence for a contribution from an intracellular calcium signaling mechanism, possibly implicating ensheathing cell adhesion molecules in promoting neurite outgrowth.     

Polyarteritis nodosa presenting as temporal arteritis in a 9-year-old child

In a household survey in Guinea-Bissau, 319 episodes of diarrhea in children were followed by interviews every second day with the aim of investigating perceived morbidity and subsequent actions taken. The majority of the mothers had good knowledge of oral rehydration salts (ORS). However, only 58% of the episodes were treated with ORS and the amount given was insufficient. Mothers with no knowledge of ORS did not use it during the observed attack of diarrhea regardless of contact with a health center, which suggests that maternal knowledge is an important determinant of whether health personnel provide ORS. Children with diarrhea considered to be caused by teething were less likely to receive ORS in the acute phase (risk ratio = 0.6, 95% confidence interval [CI] = 0.5-0.9). Univariate analyses showed that the use of ORS was related to number of reported symptoms, the mother being the care taker, consultations, previous use of ORS, good knowledge of ORS, and having ORS sachets at home. Multivariate Cox regression analyses showed that the presence of ORS sachets at home at the onset of diarrhea was the strongest predictor of use (hazard ratio = 3.3, 95% CI = 1.9-3.6). Improved health education should focus more on the quantity of ORS needed, early signs of dehydration, treatment of teething diarrhea, and breast feeding, and address mothers who have no prior knowledge of ORS. Management of diarrhea may be improved by a more liberal distribution of ORS sachets.     

Riboflavin-mediated delivery of a macromolecule into cultured human cells

The effects of perivascular nerve stimulation and phenylephrine on osmolyte release were studied in the intact perfused rat liver and isolated liver parenchymal cells (PC) and nonparenchymal cells. In the perfused liver, electrical stimulation of perivascular nerves (20 Hz/2 ms/20 V) led to a phentolamine-sensitive increase of cell hydration by 6.5% +/- 1.2% (n = 3) and a transient phentolamine-sensitive stimulation of taurine and inositol, but not betaine, release. These nerve effects were mimicked by phenylephrine, but not prostaglandin F2alpha, and were not affected by sodium nitroprusside (SNP) or ibuprofen. Nerve stimulation-induced taurine, but not inositol, release was inhibited by 4, 4'-di-isothiocyanatostilbene-2,2'-disulphonic acid (DIDS) (50 micromol/L). Single-cell fluorescence studies with isolated liver PC, Kupffer cells (KC), sinusoidal endothelial cells (SEC), and hepatic stellate cells (HSC) revealed that phenylephrine induced an increase in cytosolic free Ca2+ only in PC and HSC, but not in KC and SEC, whereas extracellular uridine triphosphate (UTP) produced Ca2+ transients/oscillations in all liver cell types studied. Phenylephrine had no effect on osmolyte release from isolated KC and SEC, but increased taurine (but not inositol) release from PC and inositol (but not taurine) efflux from HSC. The data suggest that: 1) liver cell hydration and-consecutively-osmolyte content are modulated by hepatic nerves via an alpha-adrenergic mechanism, which does not involve eicosanoids or hemodynamic changes; 2) that PC and HSC are the primary targets for nerve-dependent alpha-adrenergic activation, whereas 3) KC and SEC probably do not express alpha-adrenoceptors coupled to Ca2+ mobilization or osmolyte efflux.     

Plasmalemmal pH-gradients in drug-sensitive and drug-resistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy

31p Magnetic resonance spectroscopy (MRS) was employed to investigate tumor pH in xenografts of drug-sensitive and drug-resistant MCF-7 human breast carcinoma cells. Measured extracellular pH values were found to be lower than the intracellular pH in all three tumor types investigated. The magnitude of this acid-outside plasmalemmal pH gradient increased with increasing tumor size in tumors of two drug-resistant variants of MCF-7 cells, but not in tumors of the parent (drug-sensitive) cells. The partitioning of weak-base or weak-acid drug molecules across the plasma membrane of a tumor cell is dependent upon the acid-dissociation constant (pKa) of the drug as well as the plasmalemmal pH gradient. A large acid-outside pH gradient, such as those seen in MCF-7 xenografts, can exert a protective effect on the cell from weak-base drugs such as anthracyclines and Vinca alkaloids, which have pKa values of 7.5 to 9.5. The possibility of enhancing the therapeutic efficacy of weak-base drugs by dietary or metabolic manipulation of the extracellular pH, in order to reduce or reverse the plasmalemmal pH gradient, deserves investigation.     

Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge

Patas monkeys were twice immunized with a Schistosoma haematobium-derived recombinant glutathione S-transferase (Sh28GST) then challenged with an homologous calibrated challenge. BCG and Freund's Complete Adjuvant (FCA) were used as adjuvants in two distinct protocols. Specific IgG and IgA antibody responses were intense and homogeneous in the animals receiving Sh28GST in the presence of FCA, whereas BCG could only induce moderate and heterogeneous antibody titres. No significant effect on worm burdens was evidenced 36 weeks post-infection in either group of Sh28GST-immunized animals compared to their matched controls receiving an irrelevant protein. Although not significant, 50% reductions in the numbers of eggs located in all tissues (FCA group) and in the urogenital system (BCG group) were noted. Moreover, the total number of excreted eggs was dramatically diminished by 60% and 77% in the BCG and FCA groups, respectively. These reductions reached 75% and 80% in the urines of vaccinated monkeys. Bladder pathology was also reduced in the animals displaying the lowest urinary egg excretions. There was no clear positive or negative correlate between antibody responses and individual levels of protection. Taken as a whole, our results show that Sh28GST was capable of significantly reducing S. haematobium worm fecundity in experimentally infected primates. Although FCA induced higher levels of protection, the efficacy of BCG as an adjuvant appeared sufficient to justify consideration of the future application of this new formulation as a vaccine against human urogenital schistosomosis.     

Logical problems and misunderstandings in "Problems with dimensionless measurement models of synchrony in biological systems"

OBJECTIVE: To determine extent and nature of regional differences in distribution of canine urinary calculi. SAMPLE POPULATION: 13,552 calculus specimens: 7,056 (52.1%) from females, 6,492 (47.9%) from males, and 4 from dogs of unrecorded sex. Procedure Records were used to compile information from all specimens submitted between July 1981 and December 1995. Results from mixed-breed and various breeds of stone-forming dogs were analyzed. Interrelations of breed, sex, and age of dogs, and anatomic location and mineral composition of specimens were analyzed and compared for 6 US geographic regions. RESULTS: Struvite-, apatite-, and urate-containing calculi were reported significantly most often from female dogs of the Mountain/Pacific region. Oxalate-, silica-, and brushite-containing calculi were reported significantly most often from male dogs in the New England/mid-Atlantic (NEMA) region. Cystine-containing calculi were reported most frequently from the NEMA and South Central (SC) regions. Dogs from the NEMA region were oldest in average age at diagnosis. Significant regional differences in distribution were found for several breeds. Sex distribution of renal calculi in 11 breeds of dogs (Lhasa Apso, Yorkshire Terrier, Shih Tzu, Basset Hound, Pug, Mastiff, Bichon Frise, Doberman Pinscher, Dalmatian, English Bulldog, and Pekingese) reported to be at high risk of renal lithiasis differed among the 6 geographic regions. Renal and ureteral calculi were reported significantly most often from dogs in the South Atlantic region, and bladder and urethral calculi were reported most often from dogs in the SC region. CONCLUSIONS: Wide regional differences exist in distribution of stone-forming dogs by sex, average age at diagnosis, breed, and minerals contained within and anatomic location of calculi.     

Proteolysis of native proteins. Trapping of a reaction intermediate

When limited proteolysis of the mouse major urinary proteins by trypsin was stopped by rapid denaturation of the proteinase, a covalent adduct of the two proteins was observed. The formation of this complex required active trypsin, was favored at low pH, and could be reversed by the addition of covalent or non-covalent trypsin inhibitors. Electrospray mass spectrometry of the complex demonstrated that it was an acyl-enzyme complex, formed after an unusual exopeptidase attack on the C-terminal-Arg-Glu-OH sequence by trypsin. The complex could sequester over 50% of the trypsin in a digestion mixture, and as anticipated, the protein was an effective trypsin inhibitor.     

APIC position paper: hepatitis C exposure in the health care setting. Association for Professionals in Infection Control and Epidemiology, Inc

The Association for Professionals in Infection Control and Epidemiology, Inc (APIC), is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.