Compatibility of chewing gum excipients with the amino acid L-cysteine and stability of the active substance in directly compressed chewing gum formulation

Using L-cysteine chewing gum to eliminate carcinogenic acetaldehyde in the mouth during smoking has recently been introduced. Besides its efficacy, optimal properties of the gum include stability of the formulation. However, only a limited number of studies exist on the compatibility of chewing gum excipients and stability of gum formulations. In this study we used the solid-state stability method, Fourier transform infrared spectroscopy and isothermal microcalorimetry to investigate the interactions between L-cysteine (as a free base or as a salt) and excipients commonly used in gum. These excipients include xylitol, sorbitol, magnesium stearate, Pharmagum S, Every T Toco and Smily 2 Toco. The influence of temperature and relative humidity during a three-month storage period on gum formulation was also studied. Cysteine alone was stable at 25 degrees C/60% RH and 45 degrees C/75% RH whether stored in open or closed glass ambers. As a component of binary mixtures, cysteine base remained stable at lower temperature and humidity but the salt form was incompatible with all the studied excipients. The results obtained with the different methods corresponded with each other. At high temperature and humidity, excipient incompatibility with both forms of cysteine was obvious. Such sensitivity to heat and humidity during storage was also seen in studies on gum formulations. It was also found that cysteine is sensitive to high pressure and increase in temperature induced by compression. The results suggest that the final product should be well protected from temperature and humidity and, for example, cooling process before compression should be considered.     

IL-17 as a potential target for modulating airway neutrophilia

Several chronic inflammatory airway diseases are characterized by an increased number of neutrophils in the airways. There is evidence that the recruitment of these neutrophils can be controlled by certain T-lymphocytes. However, the mechanisms behind this T-cell control of airway neutrophilia are poorly understood. In this review, we summarize the evidence that interleukin (IL)-17 released from T-lymphocytes of the CD45RO+ subset can link the activation of these T-cells to the recruitment and activation of neutrophils. This evidence suggests that pharmacotherapeutical modulation of neutrophilic airway inflammation can be achieved using several different strategies, including inhibition of IL-17 production by cAMP elevating agents or certain nuclear factor inhibitors, neutralization of released IL-17 protein by specific anti-IL-17-antibodies, blockade of the IL-17 receptor as well as inhibition of certain MAP kinases mediating the post receptor effects of IL-17 in airway cells. Additional studies on animals in vivo and patients, respectively, are needed to further evaluate the pharmacotherapeutical potential of these strategies.     

Effect of intervention on decision making of treatment for disease progression,prostate‐specific antigen biochemical failure and prostate cancer death

Background

Patient preference for the choice of treatment modality for prostate cancer has increasingly gained attention.

Objective

To assess the impact of client‐oriented decision on long‐term mortality, disease progression and biochemical failure compared with standard treatment protocol (TP).

Methods

With data from a Finnish multicentre, randomized controlled trial with two arms [104 in the enhanced patient participation (EPP) arm and 106 in the TP arm], disease‐specific and disease‐free survival, biochemical failure with elevated prostate‐specific antigen (PSA) level and disease progression were compared between the two arms using Wilcoxon test and also Cox proportional hazards regression model.

Results

Patients in the EPP arm had a higher risk of death by 37% [HR, 1.37 (0.87–2.17)] compared with those in the TP arm. Patients in the EPP arm were at increased risk of having biochemical failure by 14% [HR, 1.14 (0.72–1.79)] and for having disease progression by 2% [HR, 1.02 (0.61–1.70)] compared with those in the TP arm. All the differences were non‐significant.

Conclusions

Patients actively involved in the choice of treatment had higher risk of prostate cancer death but only slightly increased risk of biochemical failure and clinical disease progression. These findings would provide a good reference when patient autonomy for the choice of treatment modality is addressed.     

Invasive group B streptococcal infections in Finland: a population-based study

We analyzed surveillance data on group B streptococcus (GBS) infection in Finland from 1995 to 2000 and reviewed neonatal cases of early-onset GBS infection in selected hospitals in 1999 to 2000. From 1995 to 2000, 853 cases were reported (annual incidence 2.2-3.0/100,000 population). We found 32-38 neonatal cases of early-onset GBS disease per year (annual incidence 0.6-0.7/1,000 live births). In five hospitals, 35% of 26 neonatal cases of early-onset GBS infection had at least one risk factor: prolonged rupture of membranes, preterm delivery, or intrapartum fever. Five of eight mothers screened for GBS were colonized. In one case, disease developed despite intrapartum chemoprophylaxis. Although the incidence of early-onset GBS disease in Finland is relatively low, some geographic variation exists, and current prevention practices are suboptimal. Establishing national guidelines to prevent perinatal GBS is likely to reduce the incidence of the disease.     

Boron Neutron Capture Therapy of Brain Tumors: Clinical Trials at the Finnish Facility Using Boronophenylalanine

Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61Gy (W), and the average normal brain dose from 3 to 6Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50–60Gy, were treated with BPA-based BNCT using the BPA dosage of 290mg/kg. The average planning target dose in these patients was 25–29Gy (W), and the average whole brain dose 2–3Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photon radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.     

Increased retinal image velocity after vestibular lesion

The vestibulo-ocular reflex stabilizes gaze during head movements by producing compensatory eye movements. Retinal image velocity (RIV) is defined as the difference between the eye and head velocities. The RIV of 20 vestibular schwannoma (VS) patients and 17 healthy controls was measured with a head autorotation test. The head autorotation test had a sensitivity of 80% and a specificity of 88%. The mean RIV (degree/second) +/- 95% confidence intervals of the VS patients in the 5 frequency bands of 1 to 5 Hz was respectively 4.8 (4.2 to 5.5), 11.5 (8.6 to 14.4), 21.7 (15.5 to 27.9), 25.2 (17.1 to 33.4), and 26.1 (13.1 to 39.1). The RIV of the VS patients was asymmetrically larger on the operated side (P<0.05) in the frequency band of 1 Hz. The mean RIV was significantly (P<0.05) larger in the VS patients than in the controls in the frequency bands of 1 to 4 Hz. The vestibulo-ocular reflex is inaccurate after VS surgery; but the inaccuracy may not lead to the occurrence of any symptoms.     

Effect of lateral release on patellar motion in chondromalacia: An MRI study of 11 knees

Preoperatively and postoperatively, patellar motion in 11 knees with chondromalacia was analyzed by MRI at 0°, 10°, 20°, and 30° of knee flexion. The preoperative patellar position clearly deviated from normal at 0°-10° of knee flexion. The lateral release operation corrected this deviation.     

In vitro evaluation of microcrystalline chitosan (MCCh) as gel-forming excipient in matrix granules.

Although much research has been carried out into the effects of chitosan and its chemical properties on drug release, less attention has been paid to the effects of its physical properties. The aim of this study was to characterize microcrystalline chitosan (MCCh) as a gel-forming excipient. Matrix granules containing chitosans of differing physicochemical properties (crystallinity, molecular weight, degree of deacetylation) and ibuprofen or paracetamol as model drugs were prepared. Gel formation by the chitosans in the granules and subsequent effects on drug release were studied at pH 1.2 and pH 5.8. The chitosan granules acted as slow-release formulations in the case of ibuprofen (a class-II drug in the Biopharmaceutics Classification System) but with paracetamol (class-I) no controlled-release formulation could be developed. Microcrystalline grades of chitosan had the most marked retardant effects on drug release, with the efficacy of gel formation by MCCh explaining the results. The kinetic constant for ibuprofen release (at pH 5.8) ranged from 22%.h(-1) (MCCh) to 31%.h(-1) (unmodified chitosan). The release rate was easily controlled by varying the amount or molecular weight of MCCh, and to a lesser extent by the degree of deacetylation. The effects were most pronounced when pH was markedly acidic, suggesting that MCCh granules might be particularly useful in preparing stomach-specific slow-release dosage forms.     

Melkersson-Rosenthal syndrome.

OBJECTIVES: To study characteristics of Melkersson-Rosenthal syndrome (MRS) patients with facial palsy (FP) and differences in patients treated at the Departments of Otorhinolaryngology and Dermatology. METHODS: Clinical picture of MRS was studied from patient charts at two departments. Patients with FP received a questionnaire and were examined. Tissue biopsies were searched for non-necrotizing granulomatous infiltrations typical of MRS and blood DNA for UNC-93B1 gene mutations predisposing to herpesvirus infection. RESULTS: At the Department of Otorhinolaryngology, all 18 MRS patients had FP, 9 the triad form. Two patients revealed non-necrotizing granulomatous infiltrations during acute edema episodes; another two had association with uveitis. Edema was rarely persistent and did not dominate the clinical picture. No UNC-93B1 mutations were found. At the Department of Dermatology, 2 patients had triad MRS and 15 had monosymptomatic granulomatous cheilitis with persistent edema and typical MRS histology. CONCLUSION: The clinical picture of MRS with FP differed from the current knowledge of edema-dominated MRS. More studies focusing on MRS with FP would broaden our understanding of the syndrome.     

Blood pressure in healthy men and women under laboratory and naturalistic conditions

Thirty healthy nonsmoking men and 30 women underwent a laboratory reactivity assessment with systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) recorded at rest and during behavioral (mirror image tracing, mental arithmetic, color word conflict task and a semistructured Type A interview), and physical tasks (isometric exercise and the cold pressor test). Casual SBP and DBP were measured in a physician's clinic. Four months earlier SBP, DBP and HR had been monitored during a day at work and a day at home. Readings obtained in the clinic, at rest and during stress in the laboratory were related to real-life levels, reactivity (work—home difference) and variability.

For men level of cardiovascular activation at rest and during all stressors in the laboratory correlated with levels at work and at home. The best laboratory/real-life relation was observed for SBP. Systolic blood pressure levels during stress correlated with the work—home difference. Systolic blood pressure reactivity (laboratory stress levels—rest levels) to most behavioral tasks correlated with SBP levels at work and home. Daily variability and reactivity correlated with SBP reactivity to mental arithmetic and the color word conflict task. For women, levels of SBP and HR at rest and during all stressors correlated with SBP and HR at work and at home. The best laboratory/real-life relation for women was observed for HR reactivity. Casual BP in the clinic correlated with work blood pressure but generally not with daily reactivity or variability.

We conclude that BP and HR levels measured in the laboratory generalizes to real life BP and HR in both men and women and also to real life SBP reactivity in men. Laboratory induced SBP reactivity also shows a weak relation to real life SBP levels, variability and reactivity in men.