Delivery and stability of LHRH and Nafarelin in human skin: the effect of constant/pulsed iontophoresis.

Poor absorption and stability of peptides are the major obstacles concerning the development of therapeutically relevant iontophoretic devices for the transdermal delivery of peptides. The present study examined the impact of constant and pulsed (direct/alternating) current profiles on the transport and stability of two decapeptides LHRH and Nafarelin. The stability of these peptides was studied in a physiological buffer solution, with electrical current, and when the peptide solution was exposed to the stratum corneum or to the epidermal/dermal side of human skin. Pulsed direct current profile was shown to be the most efficient in transporting both LHRH and Nafarelin across the human epidermis. Furthermore, the percentage of intact LHRH in the receiver phase was slightly higher when a pulsed current profile was used. Both the peptides were stable in a physiological buffer and under the influence of current, but LHRH was degraded especially in contact with the dermal side of the skin. Altogether five hydrolytic degradation products of LHRH were observed, and they were identified by LC-ESI/MS and LC-ESI/MS/MS. No degradation products of Nafarelin were observed. It is concluded that the pulsed direct current profile may provide at least a partial solution for the transdermal delivery of peptides in terms of improved transport efficacy and peptide stability.     

Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract

The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150–200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8 h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state.     

Mandibular asymmetry in healthy children

Facial asymmetry is a naturally occurring phenomenon that is often due to differences in the mandibular dimensions on the right and left sides. The point where normal asymmetry turns abnormal cannot be easily defined, and no standards exist by which a judgement of abnormality can be made. The aim of the present study was to assess mandibular asymmetry in healthy children and its possible fluctuation during growth. The subjects consisted of 182 healthy children (88 girls, 94 boys) who had had an orthopantomogram taken at ages 7 (mean 7.5 years) and 16 (mean 15.9 years). On digitized orthopantomograms, condylar and ramus heights on both mandibular sides were measured with a Numonics Accugrid digitizer (Numonics Co., Montgomeryville, Pa., USA) and analysed with X-metrix software (Smart Systems, Turku, Finland). A paired t-test was used to determine the significance of the differences between the sides, and ANOVA to test the significance of the change in asymmetry during growth and between genders. The results revealed a statistically significant difference between the right and left sides in condylar height at age 7 years, in ramus height at both ages, and in the condylar and ramus height at age 16 years. The present study confirms that healthy young subjects generally have a statistically significant mandibular asymmetry, which, however, is only seldom clinically significant. The decision to initiate treatment because of asymmetry has to be carefully considered, since the study further showed that mandibular asymmetry may diminish or appear during growth of healthy subjects.     

Effect of sampling site on fatty acid composition of human breast adipose tissue

The effect of sampling site and proximity of malignant tumor on the relative fatty acid composition of human breast adipose tissue was studied in 10 cases of breast cancer. The four anatomic quadrants of breast did not statistically significantly differ from each other in relation to any of the 30 fatty acids studied. Proximity of the malignant tumor did not affect the relative fatty acid composition of fat when compared with more distant sampling sites. Representative samples of breast adipose tissue for fatty acid composition analysis can be obtained from tissue adjacent to the tumor.     

Determinants for preventive oral health care need among community‐dwelling older people: a population‐based study

The aim was to study the determinants of preventive oral health care need among community‐dwelling old people. The study population consisted of 165 participants, a subpopulation in the Geriatric Multidisciplinary Strategy for Good Care of Elderly People (GeMS) study. Fifty‐five percent of the edentate participants with full dentures and 82% of the dentate had a need for preventive oral health care. In the total study population, the need for preventive care was associated with co‐morbidity (measured by means of the Modified Functional Co‐morbidity Index) odds ratios (OR) 1.2 (confidence intervals [CI] 1.0–1.5), being pre‐frail or frail, OR 2.5 (CI 1.2–5.1), presence of natural teeth, OR 4.8 (CI 2.2–10.4), and among dentate participants, the use of a removable partial denture, OR 12.8 (CI 1.4–114.4). Primary care clinicians should be aware of the high need for preventive care and the importance of nonoral conditions as determinants of preventive oral health care need.     

Exploring the efficacy of behavioral skills training to teach basic behavior analytic techniques to oral care providers

Performing oral care procedures with children with autism who exhibit noncompliance can be challenging for oral care professionals. Previous research has elucidated a number of effective behavior analytic procedures for increasing compliance, but some procedures are likely to be too time consuming and expensive for community-based oral care providers to adopt. The purpose of this study was to use Behavioral Skills Training to teach dental hygiene students and staff to implement basic function-based behavior analytic strategies to reduce noncompliance and increase their success in performing oral care exams and cleanings in vivo. All participants rapidly acquired the techniques and used them effectively during exams and cleanings following BST, and skills generalized to their completion of an X-ray procedure with several children with autism. The number of steps attempted in all procedures increased relative to baseline for all participants.