Melatonin Delivery: Transdermal and Transbuccal Evaluation in Different Vehicles

Purpose

Melatonin (MLT) could be candidate drug for treatment of several diseases because of its high antioxidant and anticarcinogenic activity and its important biological roles. The aim of this study was to assess the influence of different vehicles on the permeation of MLT through buccal and skin tissues.

Methods

Formulations were characterized in terms of rheology, drug release and permeation through human skin as well as porcine buccal mucosa. Irradiation experiments were also performed.

Results

The lowest amount of MLT released was from oral adhesive paste Orabase® (OB) and the highest from the emulsion system Montanov® 68 (M68). Skin permeation revealed high pattern for Carbopol® 940 (C940) and M68, and poor for poloxamer 407 (P407) and Pluronic® lecithin organogel (PLO). Statistical differences of MLT remaining in skin between M68 vs C940 (p?<?0.05) and M68 vs PLO (p?<?0.05) were observed. Transmucosal results showed that sodium carboxymethylcellulose (NaCMC) was the best and OB the worst vehicle. P407 and PLO followed similar behaviour. Photostability studies revealed high percentage of degradation of MLT in solution which was also similar when was loaded in OB. The rest of formulations showed low rates of degradation.

Conclusions

C940 or M68 and NaCMC can be proposed as formulations for a potential systemic effect of MLT by skin and buccal mucosa routes, respectively. However, if the intended objective is to obtain local action in the skin and buccal mucosa, the proposed formulations are M68 or P407 and PLO.

     

High expression of bfl-1 contributes to the apoptosis resistant phenotype in B-cell chronic lymphocytic leukemia

In order to identify regulatory genes involved in the development of an apoptosis-resistant phenotype in patients with chemotherapy refractory B-cell chronic lymphocytic leukemia (B-CLL) expression of apoptosis-regulating genes in B-CLL cells was quantified using cDNA arrays and RT-PCR. Data were obtained from and compared between 2 groups of B-CLL patients with either nonprogressive, indolent, previously untreated disease and with leukemic cells sensitive to in vitro fludarabine-induced apoptosis, referred to as sensitive B-CLL (sB-CLL) or with progressive, chemotherapy refractory disease and with leukemic cells resistant to in vitro fludarabine-induced apoptosis, referred to as resistant B-CLL (rB-CLL). By performing a supervised clustering of genes that most strongly discriminated between rB-CLL vs. sB-CLL a small group of genes was identified, where bfl-1 was the strongest discriminating gene (p < 0.05), with higher expression in rB-CLL. A group of apoptosis-regulating genes were modulated during induction of apoptosis by serum deprivation in vitro in a similar manner in all cases studied. However, bfl-1 was preferentially downregulated in sB-CLL as compared to rB-CLL (p < 0.05). We conclude that bfl-1 may be an important regulator of B-CLL apoptosis, which could contribute to disease progression and resistance to chemotherapy, and as such represent a future potential therapeutic target.     

Clinical education for hospital pharmacists in the Netherlands and the United States of America: Some observations

Three parameters for the quality of clinical education for hospital pharmacists are postulated: the number of pharmacists who can serve as preceptors, the depth and scope of clinical pharmacy services, and the structure of the training. Dutch hospital pharmacies exhibit consistently lower pharmacist staffing ratios than their American counterparts. For the scope of services provided in Dutch (as compared to American) hospitals, the emphasis is on pharmacokinetic consultation and handling of radiopharmaceuticals, services which require less patient involvement and are consequently less labour intensive than services, such as patient profile and drug interaction monitoring services, which are more prevalent in American hospital pharmacies. 17% Of Dutch respondents were not exposed to patient profile monitoring during their training, 16% were not exposed to drug interactions monitoring, 9.8% were not exposed to pharmacokinetic services and 8.9% were not exposed to drug information services, although these services are provided at the current worksite. Dutch hospital pharmacists are often solo practitioners maintaining a high standard of practice by focusing on core tasks and activities.     

PATELLOFEMORAL PAIN SUBJECTS EXHIBIT DECREASED PASSIVE HIP RANGE OF MOTION COMPARED TO CONTROLS

Background:

Patellofemoral pain is a common condition without a clear mechanism for its presentation. Recently significant focus has been placed on the hip and its potential role in patellofemoral pain (PFP). The majority of the research has examined hip strength and neuromuscular control. Less attention has been given to hip mobility and its potential role in subjects with PFP.

Purpose/Aim:

The purpose of this study was to compare passive hip range of motion (ROM) of hip extension and hip internal and external rotation in subjects with PFP and healthy control subjects. The hypothesis was that subjects with PFP would present with less total hip ROM and greater asymmetry than controls.

Design:

Two groups, case controlled.

Setting:

Clinical research laboratory

Participants:

30 healthy subjects without pain, radicular symptoms or history of surgery in the low back or lower extremity joints and 30 subjects with a diagnosis of PFP.

Main Outcome Measures:

Passive hip extension, hip internal rotation (IR) and hip external rotation (ER). A digital inclinometer was used for measurements.

Results:

There was a statistically significant difference (p<0.001) in hip passive extension between the control group and the PFP group bilaterally. Mean hip extension for the control group was 6.8° bilaterally. For the PFP group, the mean hip extension was −4.0° on the left and −4.3° on the right. This corresponds to a difference of means between groups of 10.8° on the left and 11.1° on the right with a standard error of 2.1°. There was no statistically significant difference (p>0.05) in either hip IR or ER ROM or total rotation between or within groups.

Conclusions:

The results of this study indicate that a significant difference in hip extension exists in subjects with PFP compared to controls. These findings suggest that passive hip extension is a variable that should be included within the clinical examination of people with PFP. It may be valuable to consider hip mobility restrictions and their potential impact on assessment of strength and planned intervention in subjects with PFP.

Level of Evidence:

2b