Skin benefits with a novel emollient-treated menstrual pad.

Manufacturers of consumer products consistently seek to improve marketed products in terms of both safety and efficacy. The desire for continued improvement is seen even in well-established products such as catamenial products which have existed in some form for thousands of years. A recent innovation in the design of menstrual pads is the addition of a surface finish of emollient for the purpose of increasing comfort during wear. The present paper presents different evaluations of such an emollient-treated menstrual pad with a novel absorbent core. These investigations demonstrated product tolerability, defined the optimal formulation and concentration of the emollient-containing finish, and demonstrated successful transfer of the emollient to the relevant skin surface. In addition, enhancement of skin moisturization, associated with exposure to the emollient-treated pad, was demonstrated by several technologies: assessment of skin moisturization by Corneometer®, skin friction testing, and skin capacitance.

Current issues in clinical research and the development of new pharmaceuticals.

As a normal part of the drug development process, U.S. pharmaceutical companies conduct many thousands of clinical trials each year. Only after a reasonable assurance of safety is made can the drug be given to patients who have the underlying medical condition that the drug is designed to treat. Patient welfare is assured by adhering to the Food and Drug Administration's interpretation of the "common rule" if the data will be used to support a licensing application. 21 CFR Part 50 sets forth the regulations along with the principles of informed consent and the use of institutional review boards (IRBs) that assure patients' rights are protected. Any potential conflict of interest on the part of a clinical investigator must be reported to the FDA. Pharmaceutical companies extensively monitor ongoing clinical trials for compliance with appropriate regulations. The recent revision of the Declaration of Helsinki governing placebo-controlled clinical trials may adversely impact drug development.

Interactions of fluoride and guanine nucleotides with thyroid adenylate cyclase.

The activation of bovine thyroid adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) by Gpp(NH)p has been studied using steady-state kinetic methods. This activation is complex and may be characterized by two Gpp(NH)p binding sites of different affinities with measured constants: Ka1 = 0.1 micro M and Ka2 = 2.9 micro M. GDP beta S does not completely inhibit the Gpp(NH)p activation: analysis of the data is consistent with a single GDP beta S inhibitory site which is competitive with the weaker Gpp(NH)p site. Guanine nucleotide effects upon F- activation of adenylate cyclase have been studied. When App(NH)p is the substrate, 10 micro M GTP along with 10 mM NaF gives higher activity than NaF alone, while GDP together with NaF inhibits the activity by 50% relative to NaF. These features are not observed when the complex is assayed with ATP in the presence of a nucleotide regenerating system or when analogs Gpp)NH)p or GDP beta S are used along with NaF. These effects were studied in three other membrane systems using App(NH)p as substrate: rat liver, rat ovary and turkey erythrocyte. No consistent pattern of guanine nucleotide effects upon fluoride activation could be observed in the different membrane preparations. Previous experiments showed that the size of soluble thyroid adenylate cyclase changed whether membranes were preincubated with Gpp(NH)p or NaF. This size change roughly corresponded to the molecular weight of the nucleotide regulatory protein. This finding, coupled with the present data, suggests that two guanine nucleotide binding sites may be involved in regulating thyroid cyclase and that these sites may be on different protein chains.

Spurious protein activators of Bordetella pertussis adenylate cyclase.

A variety of proteins and tissue preparations (rabbit erythrocyte lysate, catalase, peroxidase, creatine phosphokinase, and lima bean trypsin inhibitor) contain protein activator(s) of the extracellular adenylate cyclase of intact Bordetella pertussis organisms. Stimulation of adenylate cyclase activity of up to 1000-fold over basal activity can be obtained. Activation of the adenylate cyclase is due to the presence of calmodulin in these protein preparations. The criteria to establish this were: Ca2+ dependence of the activation, inhibition by trifluoperazine, heat stability of the activator, chromatographic behavior like authentic calmodulin, and stimulation of cyclic nucleotide phosphodiesterase by the activators. The great sensitivity of the B.pertussis adenylate cyclase assay makes this and ideal system for the detection of trace amounts of calmodulin, in the presence of large amounts of other proteins.

Calmodulin activates prokaryotic adenylate cyclase.

The adenylate cyclase of Bordetella pertussis is stimulated 100- to 1000-fold in a dose-dependent manner by calf brain calmodulin. The system has the following properties. (i) The activation is prevented by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and restored by Ca2+. (ii) Oxidation of the methionine residues of calmodulin abolishes the ability to activate the cyclase. (iii) Trifluoperazine inhibits calmodulin-activated cyclase. (iv) A troponin C preparation stimulates the B. pertussis cyclase with < 0.01 the potency of calmodulin. Although calmodulin has not been demonstrated in prokaryotes, this is an example of a (eukaryotic) calmodulin effect in a prokaryote.

Preactivation as a determinant for the size of thyroid adenylate cyclase.

The molecular weight of NaF-activated, Triton N-101-solubilized adenylate cyclase from bovine thyroid membranes has been measured by a combination of sucrose density centrifugation and gel exclusion chromatography. The physical parameters are: sedimentation coefficient, 6.6 S; Stokes radium 41 A; partial specific volume, 0.75 ml/g; molecular weight, 119,000. This is in contrast to the molecular weight (159,000) of the enzyme from the same source activated with guanosine 5'-(beta, gamma-imido)triphosphate. Both soluble adenylate cyclase enzymes are subject to cholera toxin-mediated ADP-ribosylation. This implies that the diminished molecular weight of the NaF-activated solubilized adenylate cyclase is a consequence of one of the following: loss of a GTP-binding protein and labeling of some other protein in the cyclase complex; loss of another protein not subject to cholera toxin labeling; or that two GTP-binding proteins normally reside within the catalytic complex and upon NaF activation one is lost.

Phospholipases. III. Effects of ionic surfactants on the phospholipase-catalyzed hydrolysis of unsonicated egg lecithin liposomes.

Apparent values of Km and Vmax have been measured for catalysis of hydrolysis of unsonicated egg lecithin liposomes, activated through addition of 0.4 M n-hexanol, by phospholipases A2 from bee and snake venoms and by phospholipase C from Clostridium welchii as a function of the concentration of three surfactants: hexadecylamine, hexadecyltrimethylammonium bromide, and dihexadecyl phosphate. For all three enzymes, values of Km and Vmax show little or no dependence on the concentration of these ionic surfactants, demonstrating that the liposomal surface charge is not a crucial factor in determining susceptibility to phospholipase-catalyzed hydrolysis.