Search

Aqueous solutions of pyrilamine, cimetidine, and histamine were instilled into the eyes of albino rabbits and drug levels determined as a function of time in the cornea, conjunctiva, aqueous humor, and iris-ciliary body. For all three drugs, less than 1% of the applied dose penetrates to the aqueous humor. Moreover, cimetidine and histamine are significantly less bioavailable than pyrilamine. Both cimetidine and histamine appear to bind to precorneal mucin and thus exhibit binding to conjunctival tissue with subsequent low penetration into the cornea and prolonged peak times in the aqueous humor. In addition, both drugs show binding to the iris-ciliary body as well. The influence of solution pH on the penetration of these compounds was also investigated, and a factor of two increase in aqueous levels was noted for the pH range 5-8, which encompasses the pKa's for these compounds.

Aqueous ragweed pollen extracts (20,000 PNU/ml or 78,000 PNU/ml) lose 50% of their Antigen E content within 5 months of storage at 4 degrees C. Glycerinated extracts and lyophilized ragweed pollen extracts retain their Antigen E content for over 15 months with little or no loss. The preservative phenol in aqueous extracts is destructive to Antigen E probably by protein denaturation. The stability of ragweed extracts as measured by Antigen E content is markedly enhanced with little loss after 15 month storage at 4 degrees C, when the extract is prepared as an alum precipitated suspension.

The topical antifungal agent naftifine has shown considerable potency against a broad spectrum of dermatophytes. In this study, an in vitro penetration test in human cadaver skin and an in vivo tape-stripping test were used to evaluate the penetration and antifungal activity of naftifine gel 1 percent and naftifine cream 1 percent compared with other antifungal agents. In both models, Trichophyton rubrum and T. mentagrophytes were the fungal species. Results show that naftifine gel 1 percent and naftifine cream 1 percent, in vitro and in vivo, penetrate the stratum corneum in concentrations that inhibit the growth of both fungal species. Following penetration in vitro, naftifine gel and cream were significantly more active against T. rubrum than econazole nitrate cream 1 percent. Following penetration in vivo, naftifine gel and cream were as active as econazole nitrate cream 1 percent and clotrimazole cream 1 percent against T. rubrum and T. mentagrophytes.

Rosoxacin, a new synthetic antimicrobial agent, has a wide spectrum of activity that may prove beneficial in the treatment of ocular infections. To determine the penetration of rosoxacin into ocular tissues and serum of the rabbit after topical, subconjunctival, and intravenous (IV) administration, rosoxacin levels were measured using a microbiological assay after enzymatic digestion of the ocular tissues. Quantities of rosoxacin that should prove to be of therapeutic value were detectable in the anterior segment of the eye after topical or subconjunctival administration. Subconjunctival administration also resulted in high levels in the retina and choroid area and in the optic nerve. Low levels were detected in the retina and choroid 15 minutes following IV injection; however, no detectable levels were found in the ocular tissues after this period.

This double-blind study provides evidence that skin testing with dialyzed Hymenoptera venoms is a more accurate, reliable method of diagnosing hypersensitivity to the sting of honeybee, yellow jacket, yellow hornet, white-faced hornet, and wasp than is skin testing with the corresponding whole body diagnostic allergenic extract. Furthermore, the incidence of false-positives was greatly reduced by using the dialyzed Hymenoptera venom (HDV) diagnosis. In this clinical trial, most sensitive individuals had skin test reactions greater than the diluent control at concentrations of 1 mug/ml or below. Levels of venom diagnostic of 100 mug/ml appeared to produce nonspecific local irritation. Skin test with whole body diagnostic allergenic extract did not produce a consistent differentiation between sensitive and nonsensitive individuals. No untoward reactions were seen using the dialyzed Hymenoptera venom (HDV) diagnostic.

To our knowledge, this is the first report of a topically applied, specific adenylate cyclase activator that reduces intraocular pressure. Forskolin, a novel adenylate cyclase activator, is reported to increase cyclic adenosine monophosphate (AMP) in intact cells. Cyclic AMP levels are increased with various antiglaucoma agents. Intraocular pressure in rabbits was significantly reduced with two concentrations of forskolin, 0.1% and 0.05%. Ocular hypertension was noted with 0.05% and 0.2%. No change in IOP was noted with 0.01% forskolin. The IOP lowering with 0.1% and 0.05% forskolin lasted approximately six hours. Mild, transient conjunctival chemosis was noted in the doses that decreased IOP. The contralateral control eye showed decreases in IOP, but the differences between control and tested eyes were significant by the Student's paired t test.

A simple, relatively fast, coulometric method to determine both the surface-moisture and bound-moisture content of a wide variety of lyophilized, allergenic extracts has been developed. The method has been found suitable for the detection of residual-moisture levels in both lyophilized protein and carbohydrate samples. Isothermal rate-changes in moisture desorption, normalized with respect to sample size and plotted versus time, yield desorption curves which are characteristic of several individual classes of lyophilized materials. The method, when compared to the Official Loss on Drying Procedure for Lyophilized Biologicals, has proven to be faster (1.5 hr.) and more sensitive, with increased specificity and accuracy.

Zeleznick, L. D. (CIBA Pharmaceutical Co., Summit, N.J.), H. Hankin, J. J. Boltralik, H. Heymann, and S. S. Barkulis. Purification and properties of N-acetyl-d-glucosamine kinase from Streptococcus pyogenes. J. Bacteriol. 88:1288-1295. 1964.-A kinase from Streptococcus pyogenes which catalyzes adenosine triphosphate-dependent phosphorylation of d-glucose and N-acetyl-d-glucosamine has been purified 1,500-fold. The ratio of the enzymatic activity on both substrates remained constant throughout the fractionation. Similarity in heat stability, p-hydroxymercuribenzoate inhibition, protection by either carbohydrate, and lack of repression of enzymatic activity when the bacteria were grown exclusively on one of the two substrates supports the hypothesis that kinase activity is associated with one enzyme.

A pH indicator and dextrose were incorporated into growth media as a modification of microbial microtiter methods for determining the minimal inhibitory concentration of antimicrobial drugs. This modified method was tested to evaluate the ease of reading end points by changes in the indicator color. Application of the procedure to two media, three indicators, and eight species of bacteria indicated that definitive end points could be reached as a result of indicator color change caused by acid production during bacterial growth. This method is accurate and reproducible. It is a modification which eliminates a need for plating and facilitates the reading of minimal inhibitory concentration end points.