Biopharmaceutics: Effect of Ointment Bases on Topical and Transdermal Delivery of Salicylic Acid in Rats: Evaluation by Skin Microdialysis

Microdialysis has been used to determine the concentration of salicylic acid in skin tissue and plasma periodically for 4 h to evaluate the effect of ointment bases on topical and transdermal delivery of salicylic acid. The ointment bases examined were solbase (water-soluble), poloid and white petrolatum (oleaginous), hydrophilic poloid (water in oil (w/o) type emulsion lacking water) and absorptive ointment (w/o-type emulsion containing water). The ointments (0.1 g) containing 25 μmol salicylic acid were applied for 2 h to the surface of rat skin (1 cm²) with (intact) or without the stratum corneum. For intact skin, the extent of topical delivery from different ointments, evaluated by the area under the concentration-time curve (AUC) of salicylic acid in the skin tissue (AUCskin), increased in the order solbase. white petrolatum, poloid, hydrophilic poloid. absorptive ointment. The ratio of AUC_skin (topical delivery) to the AUC of salicylic acid in plasma (AUC_plasma, transdermal delivery) varied remarkably among the different bases, the greatest ratio being observed for absorptive ointment. When the ointments were applied to skin surface without stratum corneum, AUC_skin for solbase was much higher (about 45 times that for intact skin), whereas only a small (two-fold) increase was observed for poloid and hydrophilic poloid and the increase was negligible for white petrolatum and absorptive ointment. For skin without the stratum corneum, the ratio AUC_skin/AUC_plasma for the different ointments was comparable, although the magnitudes of AUC_skin and AUC_plasma still varied substantially. The variance of AUC values arises as a result of the different rates of release of salicylic acid from the bases. These results indicate that: the topical and transdermal delivery of salicylic acid in intact skin varies substantially among different ointment bases, and the greatest topical delivery is observed for absorptive ointment; use of absorptive ointment increases the retention of salicylic acid in the stratum corneum; and the stratum corneum functions strongly as a penetration barrier for solbase, moderately for poloid and hydrophilic poloid, and less for absorptive ointment and white petrolatum.     

Trials of bright light exposure and melatonin administration in a patient with non-24 hour sleep-wake syndrome

Abstract We report a patient with non-24 h sleep-wake syndrome (non-24) whose free-running sleep-wake cycle was successfully treated with both scheduled bright light exposure and melatonin treatment. In the present study, morning bright light as well as evening melatonin phase-advanced sleep-wake cycles and melatonin rhythm. Both these procedures achieved appropriate entrainment to a 24 h day. However, the patient did not continue morning bright light therapy after the discharge. Rising at appropriate times in the morning for bright light therapy was difficult for him to continue. Melatonin treatment was better tolerated because of its ease of application.     

In-vitro Permeability to Salicylic Acid of Human,Rodent, and Shed Snake Skin

Abstract— In-vitro permeability to salicylic acid of human, rodent, and shed snake skin has been examined for the purpose of selecting model membranes for human skin corresponding to different anatomic sites, since a marked regional variation is suggested among the different sites. The greatest permeability to salicylic acid was observed in the scrotum, that of the sole was negligible. The cheek, neck, and inguinal skin seemed more permeable than the breast, back, thigh, lower leg, or foot skin. Shed snake and skin of hairless rat were found to show similar permeability to human breast and thigh skin. Wistar rat and nude mouse skin showed similar permeability to human cheek, neck, and inguinal skin.     

Phaeohyphomycosis caused by Exophiala jeanselmei in a patient with polymyalgia rheumatica

An 87‐year‐old man, a gardener in Okinawa, first noticed a tumor on the dorsum of his right hand in November 2005. He had been taking prednisolone for the treatment of polymyalgia rheumatica since 2000. A nearby dermatologist incised the tumor for pus drainage in February 2006. In April of the same year, the dome‐like tumor reappeared. The same treatment was repeated. Because the culture of the pus revealed fungi at that time, terbinafine hydrochloride and minocycline were administrated under the diagnosis of a deep fungal infection. After a short remission, the tumor recurred in November of the same year and in May and August of 2007 regardless of the repeated incision and pus drainage. He was referred to our hospital on 27 September 2007. His first physical examination at our outpatient office showed a skin‐colored, well‐demarcated, multilocular, cystic subcutaneous tumor on the dorsum of his right hand. Histopathological examination revealed a pseudocyst with fibrous walls of connective tissue. Continuous, bead‐like hyphae, positive with periodic acid‐Schiff stain and Grocott stain, were found within the pseudocyst. Morphological and molecular biological examinations of the separately cultured specimens identified the causative agent as Exophiala jeanselmei. The entire cyst was removed under local anesthesia, and an artificial dermis made of silicon membrane was applied to the wound. Skin graft was performed in November after confirming no recurrence of the fungal infection. Terbinafine hydrochloride 125 mg/day has continued. No recurrence has been observed up to now.     

Snake coiled fibres in rat soleus muscle in chloroquine induced myopathy share immunohistochemical characteristics with amyloid depositions in Alzheimer's disease brain tissue

Pathological and immunopathological studies were carried out on snake coiled fibres (SCF) which occurred in affected soleus muscle in chloroquine treated rats. The SCF began to appear in denervated soleus muscle by 8 days after chloroquine injection. By day 14, typical SCF were observed with an unusual swirling pattern of the myofibrils, presenting a bizarre appearance. By day 21 or later, the SCF became less remarkable, and were fragmented and broken apart to form large vacuoles. Immunopathological studies demonstrated that the amyloid β (Aβ ) and N and C-terminal regions of amyloid precursor protein (APP), and the amyloid associated proteins tested, apolipoprotein E (apoE), SP-40,40, α₁-antichymotrypsin (α₁-ACT), and ubiquitin, which are known to be components of amyloid depositions found in Alzheimer's disease (AD) affected brains, were present in the SCF. ApoE, SP-40,40, α₁-ACT, and ubiquitin are induced following certain cell challenges (e.g. heat shock, various drugs and injury). The significance of APP, Aβ, and amyloid associated proteins are discussed in respect to snake coiled fibre formations in chloroquine rat myopathy and in the amyloidogenesis of AD.     

Clinical characteristics of circadian rhythm sleep disorders

Abstract From our practice at the sleep disorders clinic in Kohnodai Hospital, National Center of Neurology and Psychiatry (NCNP), we report the clinical characteristics of circadian sleep-wake rhythm disorders. Nearly 90% of circadian rhythm sleep disorders were diagnosed as delayed sleep phase syndrome (DSPS) or as non-24 sleep-wake syndrome (non-24). While DSPS was equally common in males and females, non-24 was more frequently seen in men. It was of psychiatric interest that a considerable number of patients had depressive states in the course of their circadian rhythm sleep disorders. Difficulty in adapting to social life was more severe in patients with non-24 than in those with DSPS.     

Melatonin treatment for circadian rhythm sleep disorders

Abstract We administered 1–3 mg melatonin to 11 patients (eight men, three women, aged 16–46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded throughout the study periods and actigraph and rectal temperature were monitored during treatment periods. Melatonin was administered 1–2 h before the desirable bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for gradual advance expecting an hypnotic effect of the melatonin. Melatonin treatments were successful in 6/11 patients. Timing and dose of melatonin administration, together with its pharmacological properties for circadian rhythm sleep disorders, should be further studied.     

Continuous measurement of temperature in non-24 hour sleep-wake syndrome

Abstract The onset of the low temperature (LT) zone which was defined as a period when the rectal temperature was below its daily mean is a convenient circadian phase marker. In this study, we document three cases of non-24 h sleep-wake syndrome in which identification of the LT zone as an evening circadian phase marker contributed to clinical judgments. We found that the LT zone was correlated well with dim light melatonin onset. Moreover, calculating the LT zone was useful in determining phase position in irregular sleep pattern and in determining the timing of bright light therapy.