Use of solubility parameters of drug and vehicle to predict flux through skin.

The solubilities of theophylline in, and fluxes through skin from, isopropyl myristate, octanol, dimethylformamide, propylene glycol, ethylene glycol, and formamide have been determined experimentally. Values for experimental permeability coefficients (Kp) corresponding to the respective fluxes were determined from, flux/solubility = Kp, which were then compared with values for the respective theoretical partition coefficients (PC) calculated from the known solubility parameters for the vehicles (delta v), theophylline (delta i) and skin (delta s). There was a good correlation for theoretical log PC - 2.52 = experimental log Kp for vehicles exhibiting solubility parameters in the range of delta v = 12-18 (cal/cm3)1/2. This allows relative fluxes to be determined from calculated theoretical partition coefficients and experimentally determined solubilities in that range. For vehicles or mixtures of vehicles exhibiting solubility parameters in the range of delta v = 8-12 (cal/cm3)1/2 large increases in fluxes and permeability coefficients, compared with those predicted from the results in the delta v = 12-18 (cal/cm3)1/2 range, were observed because of vehicle effects on the skin caused by the similarity in solubility parameters of those vehicles to that of skin. Qualitatively, fluxes and permeability coefficients were found to be inversely dependent on drug solubility in the vehicles with a minimum that corresponded approximately to the point where delta i = delta v.

Evaluation of gallium-68 tris(2-mercaptobenzyl)amine: a complex with brain and myocardial uptake.

Previous research into development of a gallium-radiolabeled agent that crosses the blood-brain barrier has met with limited success. In this study, we focused our attention on a Ga(III) complex of a 4-coordinate amine trithiolate tripod ligand, tris(2-mercaptobenzyl) amine (S3N). The Ga(III) S3N complex is small, neutral, and lipophilic, meeting the requirements for a potential brain imaging agent. The Ga-68 complex was easily formed with a radiochemical purity of >95%. In vitro stability of the Ga-S3N complex, determined in rat serum incubated at 37 degrees C, was greater than 95% intact at 2 h by silica gel and reversed-phase radio-thin layer chromatography. Biodistribution studies conducted in female Sprague-Dawley rats showed the complex cleared rapidly from the blood with initial high liver uptake followed by rapid washout. Significant uptake was observed in the brain, with brain:blood ratios increasing from 0.11 at 2 min postinjection to 3.8 at 60 min postinjection. Uptake was also observed in the heart going from a heart:blood ratio of 2.3 at 2 min postinjection to 11 at 60 min postinjection. Molecular mechanics were used to determine the coordination number, and demonstrated that the Ga(III) complex prefers to be 4-coordinate. Imaging studies with 68Ga-S3N in a Nemestrina macaque showed significant brain uptake, similar to other lipophilic agents. The extraction of 68Ga-S3N into the brains of both rodents and primates, higher than any 68Ga agent reported in the literature, suggests that this compound may have potential as a brain imaging agent for positron emission tomography.

The effect of vehicle on the diffusion of salicylic acid through hairless mouse skin.

The solubilities of salicylic acid in, and the fluxes through, hairless mouse skin from isopropyl myristate, 1-octanol, 1-propanol, propylene glycol, and formamide have been determined experimentally. Values for permeability coefficients (Kp) corresponding to the respective fluxes were determined from: flux/solubility = Kp. These values were then compared with values for the respective partition coefficients (P) which were calculated from the known solubility parameters for the vehicles (delta v), salicylic acid (delta i), and skin (delta s). Two different delta i values were used to calculate theoretical P values, one based on the peak solubility method and the other based on calculation from group contributions (11 and 14.4 (cal/cm3)1/2, respectively). There was good correlation between the values for theoretical log P - 1.42 and experimental log Kp for the delivery of salicylic acid from vehicles exhibiting solubility parameters in the range of delta v = 10-18 (cal/cm3)1/2, when delta i was assumed to be 14.4 (cal/cm3)1/2. There was also a good correlation between the values for theoretical log P - 2.09 and experimental log Kp for vehicles exhibiting solubility parameters in the range of delta v = 7.6-10 (cal/cm3)1/2, when delta i was assumed to be 11 (cal/cm3)1/2. Two different delta i values were used because salicylic acid apparently behaves like a polar molecule in polar vehicles and a nonpolar molecule in nonpolar vehicles. Qualitatively, fluxes and permeability coefficients were found to be inversely dependent on drug solubility in the vehicles, with a minimum that corresponded approximately to the point where delta v = delta i, and the minimum within the theoretical P curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Uveal cysts in dogs: 28 cases (1989-1991).

In a 3-year retrospective study, 28 dogs were determined to have uveal cysts arising from either the ciliary body or the iris or free-floating in the anterior chamber. Golden Retrievers, Labrador Retrievers, and Boston Terriers were represented more than other breeds. Mean age of cyst development was 7.0 years in Golden Retrievers, 9.1 years in Labrador Retrievers, and 6.8 years in Boston Terriers. There was no sex predilection in any breed. Evidence of associated ocular lesions, other than visual impairment in 1 Boston Terrier, was not noticed.

Conjunctivorhinostomy: a surgical method for the control of epiphora in the dog and cat.

Conjunctivorhinostomy, a surgical technique for the control of epiphora, was developed for use in the dog and cat. The method was performed 32 times in 21 animals, with varying degrees of success. It was concluded that the technique has potential as an effective procedure.

Orbital chondroma rodens in a dog.

A chondroma rodens involving the superficial medial aspect of the right orbit was diagnosed in a 9-year-old dog referred because of chronic unilateral epiphora. Examination revealed several ophthalmic abnormalities attributable to a space-occupying mass in the superficial medial aspect of the orbit. The mass was excised; however, regrowths at the primary site necessitated additional surgical interventions. The dog was given radiation therapy, which provided encouraging results. Subtle histologic differences as well as differing epidemiologic features suggest that chondroma rodens is not analogous to the human entity of juvenile aponeurotic fibroma, to which it has been compared in the past.

Allergic conjunctivitis in a juvenile black spider monkey.

Allergic conjunctivitis in a young spider monkey (Ateles fusciceps) was diagnosed on the basis of clinical signs, histomorphologic appearance of conjunctival biopsy specimens, and response to systemic corticosteroid therapy.

Papillomatosis of conjunctiva and adnexa in dogs.

Ocular or periocular papillomatosis was diagnosed in seven dogs. The periocular tumors (in 4 dogs) were located on the eyelids or the mucocutaneous junctions of the eyelids. Six of the tumors were removed surgically, using either superficial keratectomy and conjunctival dissection or lid resection techniques; the seventh was biopsied but not removed. In all cases, confirmation of the clinical diagnosis was made by light microscopy. The differential clinical considerations included squamous cell carcinoma, basal cell carcinoma, histiocytoma, and mastocytoma. In all cases of surgical removal, the dogs were free of recurrence 6 months following surgery.

Cerebral asymmetry in the perceived duration of color stimuli.

20 right-handed males judged the duration of small and large colored circles, which were briefly exposed in the left, center, and right visual fields. Perceived duration was a logarithmic function of exposure duration and a positive function of size and chromaticity. Over-all accuracy was equivalent in the left and right visual fields, but the effects of chromaticity and duration on subjects' judgments were asymmetrical. These and other findings suggest a two-process model of time perception in which there is right hemispheric control over a visual information processor and left hemispheric control over a timer.