The glucose and lipid effects of colesevelam as monotherapy in drug-naïve type 2 diabetes.

Colesevelam has shown efficacy in adults with type 2 diabetes mellitus (T2DM) in combination with metformin-, sulfonylurea-, or insulin-based therapy, lowering hemoglobin A1c (HbA1c) and low-density lipoprotein cholesterol levels. A study was conducted to evaluate colesevelam as monotherapy in drug-naïve patients with T2DM. In this randomized, double-blind, placebo-controlled, parallel-group study, adults with T2DM who had inadequate glycemic control (HbA1c ≥7.5% and ≤9.5%) with diet and exercise alone were randomized to receive colesevelam 3.75 g/day (n=176) or placebo (n=181) for 24 weeks. The primary efficacy variable was HbA1c at week 24. Colesevelam as compared to placebo showed significant reductions from baseline in HbA1c (-2.92 mmol/mol [0.3%]; p=0.01) and fasting plasma glucose (-10.3 mg/dl; p=0.04) at week 24 with last observation carried forward. Colesevelam also significantly reduced low-density lipoprotein cholesterol (-11.2%; p<0.0001), total cholesterol (-5.1%; p=0.0005), non-high-density lipoprotein cholesterol (-7.4%; p=0.0001), and apolipoprotein B (-6.5%; p=0.0001) and increased apolipoprotein A-I (+ 2.4%; p=0.04), and triglycerides (+ 9.7%; p=0.03). Colesevelam monotherapy resulted in statistically significant improvements in glycemic and most lipid parameters in subjects with type 2 diabetes, with no new or unexpected safety and tolerability issues. Modest reductions in HbA1c and low-density lipoprotein cholesterol levels with colesevelam further support its use in combination with other antidiabetes agents when treatment targets for these parameters are close but are not quite achieved.ClinicalTrials.gov identifier: NCT00789737.

Statistics of highly heterogeneous flow fields confined to three-dimensional random porous media.

We present a strong relationship between the microstructural characteristics of, and the fluid velocity fields confined to, three-dimensional random porous materials. The relationship is revealed through simultaneously extracting correlation functions R_{uu}(r) of the spatial (Eulerian) velocity fields and microstructural two-point correlation functions S_{2}(r) of the random porous heterogeneous materials. This demonstrates that the effective physical transport properties depend on the characteristics of complex pore structure owing to the relationship between R_{uu}(r) and S_{2}(r) revealed in this study. Further, the mean excess plot was used to investigate the right tail of the streamwise velocity component that was found to obey light-tail distributions. Based on the mean excess plot, a generalized Pareto distribution can be used to approximate the positive streamwise velocity distribution.

The changing face of internal medicine: patient centred care.

Patient centred care is now considered the gold standard and there should be 'no decision about me, without me'. Internists who treat patients with complex multi-morbidities should consider patients' preferred outcomes, following a 'goal-oriented' principle. Perhaps the most important barrier to goal-oriented care is that medicine is deeply rooted in a disease-outcome-based paradigm. Rather than asking what patients want, the culture of modern medicine has prioritised optimal disease management according to guidelines and population goals. Doing what is right for the patient should be based on trust. Patients and internists must therefore meet as equals: 'I' and 'you' should be replaced by 'we'.

Engineering silica particles as oral drug delivery vehicles.

Porous silica particles are emerging as complementary systems to polyester microspheres for the encapsulation and controlled delivery of small-organic drugs. Their recent application in pharmaceutics is strengthened by well-established characterization and synthetic routes from the chemical engineering sciences. Silica is an interesting scaffold material for the encapsulation of organic molecules. It can be formed into hierarchical structures over a wide range of length scales and interconnectivities. Encapsulation can therefore be tailored not only to the drug but the desired release properties. In addition to surfactant-templating of hierarchical silica structures, polypeptides from marine organisms may offer biological routes to novel silica materials. Silica sol-gels have also been evaluated as delivery vehicles, particularly with regard to generating hybrid systems with mesoporous silica or composite xerogels. This review will first focus on the detailed characterisation of pore size and structure of mesoporous silica with regards water penetration and drug diffusion. We then describe the pharmaceutical applications of silica materials with regard to improving oral bioavailability, multiparticulate systems for gastroretention or sustained release, composite xerogels and in vivo biocompatibility.

Viral studies in rheumatic disease.

Rheumatic disease has long been thought to represent an interaction between environmental agents on a background of genetic susceptibility. In this review herpesviruses and retroviruses are considered as possible aetiological agents in autoimmune disease with a particular emphasis on Sjögren's syndrome. A possible role for cytomegalovirus, Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and human herpesvirus-8 (HHV-8) is reviewed. We conclude that there is no compelling evidence for the involvement of any of these herpesviruses. Retroviruses, however, are attracting increasing interest. In Man, both Human immunodeficiency virus (HIV) and human T lymphotropic virus type I (HTLV-I) infections cause autoimmune phenomena, including Sjögren's syndrome and arthritis in a minority of infected individuals. Similar reactions to retroviral infection are also seen in animal models. A possible role for the newly described human retrovirus-5 (HRV-5) is discussed, though current evidence does not support a role in Sjögren's syndrome. Other autoimmune diseases are under investigation.

A double blind placebo controlled trial of azathioprine in the treatment of primary Sjögren's syndrome.

OBJECTIVE: To establish whether there is a place for low dose azathioprine (AZA) as a disease modifying agent in patients with uncomplicated primary Sjögren's syndrome (SS). METHODS: Twenty-five patients with primary SS were entered into a double blind, placebo controlled trial of AZA (1 mg/kg/day) for a period of 6 months. RESULTS: Six patients, all receiving active drug, withdrew because of side effects. There was no significant change in disease activity variables when measured clinically, serologically, or histologically. CONCLUSION: This trial suggests that low dose AZA does not have a role as a disease modifying agent in SS.

Human retrovirus-5 proviral DNA is rarely detected in salivary gland biopsy tissues from patients with Sjögren's syndrome.

OBJECTIVE: To examine whether human retrovirus-5 (HRV-5) infection is associated with Sjögren's syndrome. METHODS: Salivary gland DNA was tested by nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Rigorous precautions were taken to prevent false-positive results from PCR contamination. Positive samples were confirmed by testing with an additional independent set of primers and were then sequenced. RESULTS: Ninety-two samples were examined (55 from Sjögren's syndrome patients, 37 from non-Sjögren's syndrome patients), 2 of which were positive. One was from a patient who had sicca symptoms but who did not satisfy the criteria for a diagnosis of Sjögren's syndrome. The other was from a patient with secondary Sjögren's syndrome. Owing to the extremely low virus load in minor salivary glands, the number of HRV-5-infected patients may be underestimated. In total, 3 different sequences of HRV-5 were identified which were 98% identical to the original sequence but which displayed variations between and within individuals. CONCLUSION: This is the first study to systematically seek a disease association with HRV-5, although with this method, an association with Sjögren's syndrome was not identified.

Detection of human retrovirus 5 in patients with arthritis and systemic lupus erythematosus.

OBJECTIVE: To examine whether human retrovirus 5 (HRV-5) infection is associated with autoimmune rheumatic disease. METHODS: DNA from patients with various disorders including inflammatory diseases and from normal subjects was tested by nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Positive results were confirmed by DNA sequencing. RESULTS: HRV-5 proviral DNA was detected in 53% of synovial samples from arthritic joints, in 12% of blood samples from patients with rheumatoid arthritis (RA), and in 16% of blood samples from patients with systemic lupus erythematosus. In contrast, it was not detectable by PCR of affected tissues from patients with several other autoimmune diseases and was found in only 1 of >200 tissue specimens obtained at autopsy from non-RA patients. Sequence analysis of the amplified viral segment showed genetic variation between samples with maintenance of the open reading frame, typical of a replicating infectious retrovirus. CONCLUSION: This is the first report of the frequent detection of HRV-5 in any disease. We propose that the possible involvement of HRV-5 in autoimmune and rheumatic disease should be investigated further.