Cl- channels are randomly activated by continuous GABA secretion in cultured embryonic rat hippocampal neurons

Throughout the adult vertebrate central nervous system (CNS) gamma-aminobutyric acid (GABA) mediates transient Cl- conductances commonly identified as fast, Cl(-)-dependent inhibitory synaptic signals [Prog. Neurobiol., 36 (1991) 35-92]. In the rat hippocampus Cl(-)-dependent excitatory transients mediated by GABA emerge during the first postnatal week superimposed on a steady-state baseline that is also Cl(-)- and GABA-dependent [Int. J. Dev. Neurosci., 8 (1990) 481-490]. Here we report that many embryonic rat hippocampal neurons cultured for hours to days exhibit random fluctuations in Cl- channel activity that are mediated by continuous secretion of GABA in the absence of transients. Thus, GABA is broadcast tonically before it is released transiently.     

The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and monoPEGylated rhG-CSF

PURPOSE: The objective of this study was to highlight differences in the pulmonary absorption of a monoPEGylated rhG-CSF and rhG-CSF after intratracheal instillation and aerosol delivery. METHODS: Male Sprague Dawley rats (250 g) were anesthetized and intratracheally instilled (IT) with protein solution or were endotracheally intubated and administered aerosol for 20 min via a Harvard small animal ventilator. A DeVilbiss "Aerosonic" nebulizer containing 5 ml of protein solution at approximately 3 mg/ml was used to generate aerosol. The volume of protein solution deposited in the lung lobes was estimated to be approximately 13 microliters after delivery of Tc-99m HSA solutions. The PEGylated proteins consisted of a 6 kDa (P6) or 12 kDa PEG (P12) linked to the N-terminus of rhG-CSF. rhG-CSF also was administered IT in buffers at pH 4 and pH 7 and in dosing volumes ranging from 100 to 400 microliters. Blood samples were removed at intervals after dosing and the total white blood cell counts (WBC) were determined. Plasma was assayed for proteins by an enzyme immuno assay. RESULTS: The plasma protein concentration v. time profiles were strikingly different for aerosol v. IT delivery. The Cmax values for rhG-CSF and P12 after aerosol delivery were greater than found after IT (Aerosol: 598 +/- 135 (ng/ml) rhG-CSF; 182 +/- 14 P12 v. IT: 105 +/- 12 rhG-CSF; 65.9 +/- 5 P12). Similarly, Tmax was reached much earlier after aerosol administration (Aerosol: 21.7 +/- 4.8 (min) rhG-CSF; 168 +/- 31 P12 v. IT: 100 +/- 17 rhG-CSF; 310 +/- 121 P12). Estimated bioavailabilities (F(lung)%) were significantly greater via aerosol delivery than those obtained after IT (Aerosol: 66 +/- 14 rhG-CSF; 12.3 +/- 1.9 P12 v. IT: 11.9 +/- 1.5 rhG-CSF; 1.6 +/- 0.1 P12). An increase in circulating WBC counts was induced by all proteins delivered to the lungs. The rate and extent of absorption of rhG-CSF was not influenced by the pH employed nor the instilled volume. CONCLUSIONS: Estimates of bioavailability are dependent upon the technique employed to administer drug to the lungs. Aerosol administration provides a better estimate of the systemic absorption of macromolecules.     

Altered antigen presentation in mice lacking H2-O

The phenomenon of transgenerational traumatization has currently become widely recognized and described, although the task of disentangling the underlying interactional mechanisms remains a difficult one. These transgenerational mechanisms were first detected in families of the survivors of the Holocaust, but they may be equally prominent in families of parents who have been traumatized in other ways, for example, as victims of child neglect and abuse, as orphaned children, or during military service. In cases in which parents have themselves been subjected to early parental deprivation, one or more children may become projectively identified with a parent's (posttraumatic) "bad child"-self, whereas the parent him/herself has identified with--enacts the role of--the idealized internal "martyr" parent. A case study is presented describing the individual and family therapeutic treatment of a woman who, as a child, had been traumatically separated from her parents.     

Mammalian exocrine secretions XV. Constituents of secretion of ventral gland of male dwarf hamster, Phodopus sungorus sungorus

In a study aimed at the chemical characterization of constituents of the ventral gland secretion of the male dwarf hamster, Phodopus sungorus sungorus, 48 compounds, including saturated alcohols, saturated and unsaturated ketones, saturated and unsaturated straight-chain carboxylic acids, iso- and anteisocarboxylic acids, 3-phenylpropanoic acid, hydroxyesters, 2-piperidone, and some steroids were identified in the secretion. The position of the double bonds in -icosadienyl--butyrolactone and -henicosadienyl--butyrolactone, and the position of methylbranching in seven C₁₆–C₂₁saturated ketones could not be established. Several constituents with typically steroidal mass spectra also remained unidentified. The female dwarf hamster's ventral gland either does not produce secretion or produced so little secretion that it was impossible to collect enough material for analysis.     

Formation kinetics of hydroxymethylfurfural and brown coloured compounds in goat milk during heating

The formation of hydroxymethylfurfural, nonenzymatic brown coloured compounds and free sulphydryl groups in goat milk was studied during heating at 75–95 °C. Analysis of kinetic data suggested that formation of hydroxymethylfurfural and nonenzymatic brown coloured compounds followed zero order reaction kinetics, while formation of free sulphydryl groups during heating varied depending on heating time. A good linear correlation (r = 0.839) was found between brown coloured compounds and hydroxymethylfurfural content in milk samples during heating. Activation energies (E_a) for the formation of hydroxymethylfurfural and nonenzymatic brown coloured compounds were 96.31 and 69.79 kJ/mol, respectively.