Effect of carboxylic acids on permeation of chlorpromazine through dimethyl polysiloxane membrane

The effect of carboxylic acids on the permeation of chlorpromazine was investigated through a dimethyl polysiloxane nonpolar membrane. The permeability of the diffusate, at pH 5.8, increases considerably in the presence of carboxylic acids or phosphate, probably due to an ion-pair formation between the relative anions and chlorpromazine.     

Diurnal rhythms in pineal N-acetyltransferase and hippocampal norepinephrine: effects of water deprivation, blinding and hypothalamic lesions

The pineal gland in the rat exhibits a diurnal rhythm in activity of the enzyme serotonin N-acetyltransferase (N-AT) with peak values during the dark period of a diurnal lighting schedule approximately 100-fold those during the light period. After blinding the rhythm becomes free-running. It is abolished by partial hypothalamic deafferentation with a knife cut made caudal to the optic chiasm. Water deprivation for 23 h daily has no effect on the pineal rhythm in either intact, blinded or deafferented animals. In contrast to this, there is a diurnal rhythm in hippocampal formation in norepinephrine content which can be entrained by a water deprivation schedule in both intact and blinded animals. These observations indicate that in the same animals 1 diurnal rhythm may remain entrained to the light-dark cycle while another rhythm is entrained to a secondary synchronizer, the water deprivation schedule.     

Mechanism of production of intestinal secretion by negative luminal pressure

The relationships between luminal hydrostatic pressure and fluid transport by dog jejunum in vivo studied as a sheet in the Wells clamp were compared with quantitative predictions from a model proposed for the mechanism of the secretion produced by elevated venous pressure. According to the model, the secretion produced by increasing venous pressure and the secretion produced by negative luminal pressure are both passive filtrates contingent on a transepithelial pressure of a few centimeters of H2O. We consider that the agreement between the observed and predicted responses to luminal pressure provides strong support for the model. In particular, a) the observations displayed a predicted gross asymmetry in rates of fluid transfer with isotonic fluids depending on whether the luminal pressure was positive or negative; b) the observed magnitude of the negative luminal pressure required for the onset of secretion agreed with predictions; and c) the secretion contained significant amounts of protein at about 25% of the plasma concentration.     

The pharmacokinetics of ephedrine after oral dosage in asthmatics receiving acute and chronic treatment

1 Ephedrine plasma levels have been measured in ten asthmatic patients given a singel dose of ephedrine hydrochloride (22 mg) along and in combination with theophylline and a barbiturate. 2 Pharmacokinetic assessment of the data indicated no significant intra-subject changes in kinetic parameters before or after chronic treatment with ephedrine HCl (11 mg three times a day) alone or in combination. 3 Tolerance to these therapeutic doses, if it occurs, is therefore not disposition-related but rather to pharmacodynamic changes.     

Purification and characterization of two forms of urokinase

Affinity chromatography on agmatine-Sepharose was used for the separation of two active forms of urokinase (EC 3.4.99.26) from partially purified human urinary urokinase. The approximate molecular weight of the heavier form was 47 000 and of the lighter 33 400. Both forms were homogeneous by sodium dodecyl sulfate gel electrophoresis and by 3H-labeled diisopropylphosphorofluoridate and 14C-labeled p-nitrophenyl-p'-guanidinobenzoate incorporation studies. The 33 400 mol. wt. form had a single chain, and the 47 000 mol. wt. form had two chains (33 100 and 18 600 mol. wt.) linked by disulfide bonds. The specific activity of the heavier form was 104 000 CTA units/mg protein, compared with 226 000 units/mg for the lighter form but the activities per mmol of active site (molar activities) of the two forms were almost identical (9.6-10(9) and 10.2-10(9) CTA units/mmol). Isoelectric focusing on gels showed that the 47 000 material contained one major subform with a pI of 8.60 and a minor subform with a pI of 8.90, while the 33 400 material had three major subforms with pI values of 8.35, 8.60 and 8.70, respectively, and a minor subform with a pI of 8.05. 3H-labeled diisopropylphosphorofluoridate incorporation studies revealed an active-site serine residue in the heavy chain.     

Cutaneous CD30+ lymphoproliferative disorders: expression of bcl-2 and proteins of the tumor necrosis factor receptor superfamily

The spectrum of CD30+ cutaneous lymphoproliferative disorders is characterized by the histology of a high-grade lymphoma but frequent clinical regression of skin lesions in lymphomatoid papulosis (LyP) and occasional regression in CD30+ large cell lymphomas (LCLs). A recent study shows that apoptosis may be a significant mechanism of regression of LyP (Arch Dermatol 133:828-833, 1997). Therefore, we studied expression of proteins that induce apoptosis, including CD27, CD40, CD95, and nerve growth factor receptor (NGF-R), as well as anti-apoptotic protein bcl-2 in skin lesions from 25 patients within the spectrum of CD30+ cutaneous lymphoma. Our results show consistent expression of CD95 (APO-1/Fas), but rare or absent expression of CD27, CD40, and NGF-R on tumor cells from both regressing LyP lesions and nonregressing CD30+ lymphomas. Bcl-2 was expressed at low levels in LyP and at high levels in pleomorphic CD30+ lymphomas. These results indicate that, in addition to CD30, CD95 expression is preferentially expressed at high levels in all cutaneous CD30+ lymphomas and suggest that CD95 may play a role in the regression of CD30+ skin lesions. Expression of bcl-2 appears to protect tumor cells from apoptosis in CD30+ lymphoproliferative disorders.     

Reconfiguration of carrier assignment in cellular networks

We consider the problem of updating nominal carrier assignments in cellular networks, which dymamically operate with channel borrowing and reassignments, to match the timevarying offered traffic demands encountered on these systems. Assuming an existing assignment of nominal carriers and the new requirements in each cell, we formulate the problem of obtaining a new assignment such that the number of carriers required to meet the total traffic demand as well as the number of different assignments between the old and the new allocation are minimized. We introduce two approaches to obtain this new assignment. One approach treats the two objectives independently and is applicable to problems with cochannel interference constraints only. This approach produces a new assignment optimized with respect to the first goal, and then rearranges the frequencies of this new allocation so that the number of different assignments with respect to the previous allocation is minimum. A second approach aims at satisfying both goals at the same time and is applicable to problems with any type of interference constraints. The main advantage of this approach is the introduction of a single window parameter which can control the assignments produced, by favoring one goal at the expense of the other. We study several transition scenarios in macrocellular and microcellular environments, and show that in the majority of cases these objectives are conflicting, and that reconfiguration strongly depends on the amount of change of the traffic requirements.     

Molecular alterations in early gastric carcinomas. No apparent correlation with Helicobacter pylori status

The effect of nitric oxide (NO) donors on high-voltage-activated Ca2+ channels in insulin-secreting RINm5F cells was investigated using the patch-clamp technique in the whole-cell configuration. Sodium nitroprusside (SNP, 2-400 microM) induced a dose-dependent reduction in Ba2+ currents with maximal inhibition of 58%. The IC50 for SNP was 45 microM. A different NO donor, (+/-)S-nitroso-N-acetylpenicillamine (SNAP, 500 microM), also produced a 50% decrease in current amplitude. When 200 microM SNP was administered together with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidozoline-1-oxyl-3-oxide (carboxy-PTIO, 300 microM), the Ba2+ current inhibition was lowered to 7%. Administration of 500 microM 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP) mimicked the effects of SNP, causing a comparable decrease (56%) in peak-current amplitude. When soluble guanylyl cyclase was blocked by 10 microM 1H-[1,2, 4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), the inhibitory effect of 200 microM SNP was reduced from 39% to 15%. The SNP-induced current decrease was 36% of controls after the blockade of L-type Ca2+ channels and 30% in the presence of 2.5 microM omega-conotoxin-MVIIC. These data indicate that NO inhibits both L-type and P/Q-type Ca2+ channels in RINm5F cells, probably by an increase in the intracellular levels of cGMP. NO may then significantly influence the Ca2+-dependent release of hormones from secretory cells as well as that of neurotransmitters from nerve terminals.