Passive Diffusion of Transdermal Glucose: Noninvasive Glucose Sensing Using a Fluorescent Glucose Binding Protein

The motivation for this study was to determine if a statistically significant correlation exists between blood glucose (BG) and transdermal glucose (TG) collected by passive diffusion. A positive outcome will indicate that noninvasive passive TG diffusion is a painless alternative to collecting blood through a break on the skin. Sampling involves placing a small volume of buffer solution on the surface of membrane or skin for 5 minutes. The sample is then assayed with fluorescent GBP. In vitro testing was done on regenerated cellulose and a porcine skin model to determine diffusion of standard glucose solutions. In vivo testing was done on a healthy subject and a subject with type 2 diabetes. Glucose diffused readily through the regenerated cellulose membrane with good correlation between surface and internal glucose concentrations (R ² = .997). But the porcine skin model required a surface prewash to achieve the same good correlation R ² = .943). Based on this, an optimum prewash step was determined for the in vivo studies. The resulting correlation coefficients between TG and BG after a 15-minute prewash in a healthy subject and type 2 subject were .87 and .93, respectively. Removal of the extraneous glucose in the skin by prewashing was an important step in achieving good correlation between TG and BG. The results suggest that passive collection of TG is a noninvasive alternative to current practice of breaking the skin. Further studies are under way to determine the lag time between TG and BG and for the sampling protocol to be more amenable to point-of-care application.     

Rivastigmine patch for treatment of Alzheimer's disease in clinical practice in Thailand

Background: Rivastigmine is a cholinesterase inhibitor for treatment of mild to moderate Alzheimer's disease (AD) and dementia associated with Parkinson's disease. The new patch formulation was recently made available. We assessed the safety, tolerability, and cognitive outcome of rivastigmine patch in treatment of mild to moderate AD in clinical practice in Thailand. Methods: A multicentre, hospital‐based, prospective observational study was conducted in nine hospitals across Thailand. Patients with probable mild to moderate AD who received the rivastigmine patch were enrolled. Data were collected data at baseline, weeks 4–8 and after week16. Results: A total of 116 AD patients were screened, and three were excluded. Of 113 patients, 62.8% were women with a mean age of 73.3 ± 9.2 years; 79.7% were newly diagnosed. One‐third of all patients had been using antipsychotic or antidepressant medication. Common comorbidities were hypertension and dyslipidemia. The Thai Mental State Examination score significantly increased from 18.6 to 20.3 (weeks 4–8) and 20.4 (week 16+) (P < 0.001). Scores based on physicians’ (Clinical Global Impression) and caregivers’ (Patients’ Caregiver Global Impression of Change) impressions of improvement suggested minimal improvement. Because of adverse events, seven patients's dosages were reduced 10 cm² to 5 cm² or from 5 cm² to nothing. Itching was the most common adverse symptom. Conclusions: During the first 16 weeks after initiation of rivastigmine patch therapy, patients with probable mild to moderate AD had statistically significant improvement in cognitive function, but clinically marginal benefit. Rivastigmine was safe and well tolerated.     

Novel DYSF mutations in Thai patients with distal myopathy

Dysferlinopathy refers to a variety of autosomal recessive, skeletal muscle disorders due to the mutations of dysferlin-encoding gene, DYSF. It encompasses limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), distal myopathy with anterior tibial onset (DMAT), isolated hyperCKemia, rigid spine syndrome and congenital muscular dystrophy. Herein, we report five Thai patients with distal myopathy due to dysferlinopathy including four MM and one DMAT patients. Muscle biopsy from one MM patient depicted numerous ring fibers which is an atypical finding in dysferlinopathy. Mutation analysis of DYSF revealed novel compound heterozygous mutations of p.Tyr309X and c.236 + 1G > T in two related MM patients, known homozygous mutations, p.Arg89X and p.Gln176X, in two MM patients and a heterozygous missense mutation, p.Arg555Trp, in a DMAT patient. Most of the previously reported DMAT patients were Hispanic. To the best of our knowledge, this is the first report of genetically confirmed patients with dysferlinopathy in Thailand.     

Fluorescence Glucose Sensing,Part II: Detection of Trace Glucose on the Surface of a Semipermeable Membrane Using a Fluorescently Labeled Glucose-Binding Protein: A Promising Approach to Noninvasive Glucose Monitoring

Background

Our motivation for this study was to develop a noninvasive glucose sensor for low birth weight neonates. We hypothesized that the underdeveloped skin of neonates will allow for the diffusion of glucose to the surface where it can be sampled noninvasively. On further study, we found that measurable amounts of glucose can also be collected on the skin of adults.

Method

Cellulose acetate dialysis membrane was used as surrogate for preterm neonatal skin. Glucose on the surface was collected by saline-moistened swabs and analyzed with glucose-binding protein (GBP). The saline-moistened swab was also tested in the neonatal intensive care unit. Saline was directly applied on adult skin and collected for analysis with two methods: GBP and high-performance anion-exchange chromatography (HPAEC).

Results

The amount of glucose on the membrane surface was found (1) to accumulate with time but gradually level off, (2) to be proportional to the swab dwell time, and (3) the concentration of the glucose solution on the opposite side of the membrane. The swab, however, failed to absorb glucose on neonatal skin. On direct application of saline onto adult skin, we were able to measure by HPAEC and GBP the amount of glucose collected on the surface. Blood glucose appears to track transdermal glucose levels.

Conclusions

We were able to measure trace amounts of glucose on the skin surface that appear to follow blood glucose levels. The present results show modest correlation with blood glucose. Nonetheless, this method may present a noninvasive alternative to tracking glucose trends.     

Prevalence,clinical features and treatment outcomes of patients with myasthenia gravis positive for antibodies to muscle-specific kinase in Thailand

A small but variable subgroup of patients with myasthenia gravis (MG) who have antibodies to muscle-specific kinase (MuSKAb-MG) can present with distinct phenotypes and are often treatment-resistant. The prevalence, clinical phenotypes and outcomes of treatment of patients with MuSKAb-MG in Thailand were determined. Eight (16.3%) of the 49 patients with generalized MG who were negative for acetylcholine receptor antibodies (AChRAb) were positive for muscle-specific kinase antibodies. Most patients had predominant oculobulbar features and respiratory failure occurred in three. At follow up, three out of the seven patients who underwent thymectomy were in complete stable remission and four had improved and were on reduced immunosuppression medication, suggesting a possible benefit of thymectomy.     

Association between HLA‐B*1502 and carbamazepine‐induced severe cutaneous adverse drug reactions in a Thai population

Carbamazepine (CBZ) has been reported as the most common culprit drug for Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in several Asian countries including Thailand. A strong association between HLA‐B*1502 and CBZ‐induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case–control study was conducted to determine whether HLA‐B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population. Among 42 CBZ‐induced patients with SJS/TEN, 37 (88.10%) patients carried the HLA‐B*1502 while only 5 (11.90%) of the CBZ‐tolerant controls had this allele. The risk of CBZ‐induced SJS/TEN was significantly higher in the patients with HLA‐B*1502, with an odds ratio (OR) of 54.76 [95% confidence interval (CI) 14.62–205.13, p = 2.89 × 10^?12]. The sensitivity and specificity of HLA‐B*1502 for prediction of CBZ‐induced SJS/TEN were 88.10%. By assuming a 0.27% as a prevalence rate of CBZ‐induced SJS/TEN in a Thai population, the positive predictive value (PPV) and negative predictive value (NPV) of the HLA‐B*1502 were 1.92% and 99.96%. Results from this study suggest that HLA‐B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ‐induced SJS and TEN.