Transdermal permeation-enhancing activities of some inorganic anions

Effects of sodium salts of various monovalent inorganic anions on transdermal permeation of salicylic acid were investigated. In in-vitro experiment using a Franz-type diffusion cell and excised mouse skin, the permeation-enhancing activities of the sodium salts of inorganic anions were roughly proportional to lyotropic Hofmeister swelling abilities of the anions; F^?<SO₄ ^2?<Cl^? <ClO₄ ^?<NO₃ <SCN^? <Br <I^?, i.e. l, Br and SCN increased the flux of drugs through the mouse skin, while F^?, SO₄ ^2?, Cl^?, ClO₄ ^? and NO₃ ^? decreased or did not affect the flux. In invivo experiment using the rabbit as the test animal, the plasma concentration of salicylic acid of the rabbit to which 10%-salicylic acid ointment containing 5%-Nal or NaBr was applied was significantly higher than that of the rabbit to which the ointment without the electrolytes was applied. The amounts of sterol leached out of stratum corneum sheet when the sheet was immersed in aqueous solutions of Nal, NaBr, or NaSCN were much more than that of stratum corneum immersed in aqueous solutions of the other inorganic anions. The FTIR/ATR spectroscopy showed that the peaks at 2853 cm^?1 and 2924 cm^?1 in the IR absorption spectrum of the stratum corneum sheet of the mouse were shifted to higher frequencies by the anions which enhanced the transdermal drug permeation, while not shifted by the anions which did not have any permeation-enhancing activities or have permeation-reducing activities. These results suggest that sodium salts of some anions such as iodide, bromide and thiocyanate enhance transdermal permeation of salicylic acid through swelling and perturbation of the skin structure by these anions.     

Sensitive trace-first liquid chromatographic determination of 4-aminopyridine in 3,4-diaminopyridine

For the treatment of human neuromuscular diseases, 3,4-diaminopyridine (DAP) is six to ten times more effective than 4-aminopyridine (AP), but only half as convulsant and toxic. Therefore, there is a need for the determination of AP in DAP. With only conventional equipment, high-pressure liquid chromatography can be used for the extremely sensitive detection of a trace contaminant under one condition: that is, the trace must be eluted before the major component it contaminates. Prior elution presents a trace peak in a fully exploitable form that is maximally efficient and maximally observable. This has already been demonstrated with a Pirkle-concept chiral stationary phase for determination of a chiral trace. However, its application to determination of a nonchiral trace with a reversed phase has not previously been reported. Such an application is reported here. In this demonstrative study, selectivity and loading capability were iteratively improved. Ion pairing with dodecanesulfonate maximized selectivity. It was again shown that using a less concentrated sample in greater volume maximizes loading capability without obscuring the peak of the trace. Eventually, the ability to detect 0.005% AP in DAP was demonstrated. Whether that sensitivity might be improved still more, perhaps with a larger column, was not established.     

The filter properties of the arterial beds of organs in rats.

The frequency properties of arterial beds in organs were studied by temporarily ligating the renal, the gastric, the splenic or the superior mesenteric arteries of rats. Blood-pressure waves of the tail arteries were recorded before and during the ligations, and were analysed by Fourier's transformation. Their frequency spectra have been found to change profiles following specific patterns with the ligations of different arteries. The results were significant with regard to the frequency selectivities of the organic arterial beds. Such frequency properties can be clearly explained when the circulation system is viewed as an electrical circuit network in which the organic arterial beds work as filters.     

Molecular epidemiology and control of nosocomial methicillin-resistant Staphylococcus aureus infection in a teaching hospital.

BACKGROUND AND PURPOSE: Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection is difficult to control. Due to a dramatic increase in the nosocomial MRSA infection rate at our hospital from 2000 to 2001, this study was conducted to identify the source of these infections and the effectiveness of control measures. METHODS: 179 healthcare workers (HCWs) were screened for carriage of MRSA. Starting in April 2001, all patients with MRSA infection or colonization were put in strict contact and cohort isolation. The bacterial isolates of HCW carriers and patients with MRSA infection from April 2001 to September 2001 were subjected to antimicrobial susceptibility testing by disk-diffusion method and molecular typing by pulsed-field gel electrophoresis (PFGE). RESULTS: Fifteen HCWs were found to be carriers of MRSA. They were all given topical mupirocin treatment. After these interventions, the nosocomial MRSA infection rate decreased from 1.23 to 0.53 per 1000 patient-days. All 61 MRSA isolates available for antimicrobial susceptibility testing and molecular typing were multidrug resistant. PFGE study revealed 2 predominant types, type C and type Y, comprising 36 and 12 isolates, respectively. CONCLUSIONS: The current study demonstrates the importance of measures to control nosocomial MRSA infections in hospitals that already have a high incidence of endemic MRSA infection. Elimination of carriage by healthcare workers, and strict contact and cohort isolation are the main effective measures.     

Lack of evidence for fecal-oral transmission of Helicobacter pylori infection in Taiwanese.

BACKGROUND AND PURPOSE: Helicobacter pylori infection is primarily acquired in early childhood and its transmission routes are debated. The aims of this study were to determine the seroprevalence of anti-H. pylori immunoglobulin G (IgG) in Taiwanese and to investigate whether a common mode of transmission could be shared between H. pylori and hepatitis A virus (HAV). METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to investigate the prevalence of H. pylori among 924 healthy volunteers aged less than 40 years, and radioimmunoassay for HAV infection was conducted in 500 subjects from the same population. The kappa statistic was used to measure the difference in positivity for the 2 infections in a subgroup of 500 subjects who had their sera simultaneously tested for anti-H. pylori and anti-HAV antibodies. RESULTS: The seroprevalence of anti-H. pylori IgG was 16.7% in subjects aged < 16 years and 38.3% at ages >or= 16 years. Most children (99%) under the age of 16 were seronegative for HAV. The prevalence of H. pylori infection increased rapidly with age, at 1%/year and 0.8%/year for children and adults, respectively. The rate of H. pylori infection was higher in male (21%) than in female (12%) children (p < 0.01; OR, 2.0; 95% confidence interval, 1.2 to 3.0). No significant difference in seroprevalence between genders was noted in subjects aged >or= 16 years. The agreement in the trend of seropositivity between both infections in the age groups 1 to 10 years and 10 to 20 years was worse than chance (kappa = -0.56) and little better than chance (kappa = 0.01), respectively. CONCLUSIONS: Acquisition of H. pylori infection occurs at a young age, and male children are more likely to develop the infection. The main transmission route of HAV, the fecal-oral route, did not seem to be responsible for H. pylori transmission in this Taiwanese cohort.     

Treatment of congenital cystic adenomatoid malformation-does resection in the early postnatal period increase surgical risk?

OBJECTIVE: The recent development of fetal ultrasonography has allowed for an increasing number of prenatal diagnoses for congenital cystic adenomatoid malformation (CCAM). However, the appropriate surgical timing of these patients has not been studied as of yet. The aim of this study is to suggest a safe strategy for the treatment of CCAM by identifying the relationship between the timing of surgery and postoperative outcome. METHODS: Between 1987 and 2003, 40 patients (28 males, 12 females) underwent surgical resection for CCAM. The mean age was 38.6+/-9.1 (2 days-13 years) months. CCAM was diagnosed by prenatal ultrasonography in eight patients. Early operations were performed in four out of the eight. Operation was deferred until 2-12 months of age for the remaining four patients. RESULTS: Type I CCAM was found in 20 patients, type II in 20 and no patient exhibited type III. Five patients had associated pectus excavatum anomaly. There were no cases of operative mortality. Seventeen minor postoperative complications developed in 16 patients (40.0%): prolonged chest tube drain in 10, wound infection in 4, and 1 case of pneumonia, empyema and pleural space, respectively. The average hospital stay was 11.8 (6-29) days. During the mean follow-up period of 67.5 months, one patient died of accidental aspiration 7 months after operation during the postoperative recovery course of Ravich operation for pectus excavatum. The remaining patients reported doing well with normal physical activity. All five patients who underwent surgery at the age of under 1 month did not exhibit increased postoperative morbidity. CONCLUSIONS: We concluded that surgery for CCAM could be safely performed in all age groups with satisfactory long-term outcomes. It is suggested that early elective surgical correction can be recommended for a patient whose diagnosis was made in utero.     

Adult bipolar disorder is continuous with pediatric bipolar disorder.

Considerable debate exists regarding the continuity of bipolar disorder (BD) in children and adolescents. Do affected children continue to have BD as adults? Are pediatric forms of BD distinct from adult forms of the disorder? Here, I argue that, in fact, strictly defined BD I and II in children and adolescents is continuous with adult BD. First, if we take developmental differences into account, children and adults share similar symptoms, since they are both diagnosed according to DSM-IV criteria. Next, retrospective studies indicate that 50% to 66% of adults with BD had onset of their disorder before age 19 years. Early prospective data indicate that adolescents with BD progress to become young adults with BD. Further, family studies of pediatric BD probands find high rates of BD in adult relatives, and pediatric offspring of parents with BD have elevated rates of BD, compared with control subjects. Finally, biological characteristics of pediatric BD (such as treatment response, neurobiology, and genetics) are either shared with adults having BD or fit logically into developmental models of BD. Thus, while not conclusive, a preponderance of data support the hypothesis that pediatric BD is continuous with adult BD. Prospective studies incorporating phenomenological and biological assessment are needed to decisively address this issue.