Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study

<p>Abstract</p> <p>Background</p> <p>It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP) by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation of intestinal barrier function. Our current objective was to corroborate the favourable effect of ATP on indomethacin-induced permeability changes in healthy human volunteers when ATP is administered via enteric-coated capsules, which is a more practically feasible mode of administration. Since ATP effects may have been partly mediated through its breakdown to adenosine, effects of encapsulated adenosine were tested also.</p> <p>Methods</p> <p>By ingesting a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by five-hour collection of total urine, small intestinal permeability was assessed in 33 healthy human volunteers by measuring the urinary lactulose/rhamnose excretion ratio. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal permeability of the small intestine was assessed as a control condition (no indomethacin, no ATP/adenosine). As a model of increased small intestinal permeability, two dosages of indomethacin were ingested at 10 h (75 mg) and 1 h (50 mg) before ingesting the lactulose/rhamnose test drink. At 1.5 h before indomethacin ingestion, two dosages of placebo, ATP (2 g per dosage) or adenosine (1 g per dosage) were administered via enteric-coated hydroxypropyl methylcellulose (HPMC) capsules with Eudragit^©L30D-55.</p> <p>Results</p> <p>Median urinary lactulose/rhamnose excretion ratio (g/g) in the control condition was 0.032 (interquartile range: 0.022–0.044). Compared to the control condition, lactulose/rhamnose ratio after ingestion of indomethacin plus placebo was significantly increased to 0.039 (0.035–0.068); P < 0.01). The indomethacin-induced increase was neither affected by administration of encapsulated ATP (0.047 (0.033–0.065)) nor adenosine (0.050 (0.030–0.067)). Differences in L/R ratios between the conditions with indomethacin plus placebo, ATP or adenosine were not significant.</p> <p>Conclusion</p> <p>In this study, either ATP or adenosine administered via enteric-coated capsules had no effect on indomethacin-induced small intestinal permeability changes in healthy human volunteers. The observed lack of effect of encapsulated ATP/adenosine may have been caused by opening of the enteric-coated supplement at a site distal from the indomethacin-inflicted site. Further studies on site-specific effectiveness of ATP/adenosine on intestinal permeability changes are warranted.</p

The association of spinal osteoarthritis with lumbar lordosis

<p>Abstract</p> <p>Background</p> <p>Careful review of published evidence has led to the postulate that the degree of lumbar lordosis may possibly influence the development and progression of spinal osteoarthritis, just as misalignment does in other joints. Spinal degeneration can ensue from the asymmetrical distribution of loads. The resultant lesions lead to a domino- like breakdown of the normal morphology, degenerative instability and deviation from the correct configuration. The aim of this study is to investigate whether a relationship exists between the sagittal alignment of the lumbar spine, as it is expressed by lordosis, and the presence of radiographic osteoarthritis.</p> <p>Methods</p> <p>112 female subjects, aged 40-72 years, were examined in the Outpatients Department of the Orthopedics' Clinic, University Hospital of Heraklion, Crete. Lumbar radiographs were examined on two separate occasions, independently, by two of the authors for the presence of osteoarthritis. Lordosis was measured from the top of L₁to the bottom of L₅as well as from the top of L₁to the top of S₁. Furthermore, the angle between the bottom of L₅to the top of S₁was also measured.</p> <p>Results and discussion</p> <p>49 women were diagnosed with radiographic osteoarthritis of the lumbar spine, while 63 women had no evidence of osteoarthritis and served as controls. The two groups were matched for age and body build, as it is expressed by BMI. No statistically significant differences were found in the lordotic angles between the two groups</p> <p>Conclusions</p> <p>There is no difference in lordosis between those affected with lumbar spine osteoarthritis and those who are disease free. It appears that osteoarthritis is not associated with the degree of lumbar lordosis.</p

Integrating Teaching Skills and Clinical Content in a Faculty Development Workshop

Incorporating clinical content into medical education faculty development programs has been proposed as a strategy to consolidate faculty continuing medical education time and enhance learning. We developed a faculty development program for ambulatory internal medicine preceptors that integrated primary care genetics with ambulatory precepting. The instructional strategies addressed both areas simultaneously and included facilitated discussions, mini-lectures, trigger tapes, and role plays. To evaluate the program, we conducted a pre-post trial. Skills were measured by retrospective pre-post self-reported ratings and behaviors by self-reported implementation of commitment to change (CTC) statements. Participants' (N = 26) ambulatory precepting and primary care genetics skill ratings improved after the intervention. They listed an average of 2.4 clinical teaching CTC statements and 2.0 clinical practice CTC statements. By 3 months after the workshop, preceptors, as a group, fully implemented 32 (38%), partially implemented 35 (41%), and failed to implement 18 (21%) CTC statements. The most common barrier to clinical teaching change was insufficient skills (8 of 25; 32%) and to clinical practice change was lack of a suitable patient (15 of 25; 60%). Integrating clinical content with clinical teaching in a faculty development workshop is feasible, can improve clinical and teaching skills, and can facilitate behavior change

Relationship of serum Vitamin D concentrations with Adipokines and Cardiometabolic risk among non-Hispanic black type 2 diabetic and non-diabetic subjects: a cross-sectional study

Abstract Background To report the association of serum 25-hydroxyvitamin D [25(OH)D] and its association with adipokines and cardiometabolic risk factors in Haitian Americans (HA) and African Americans (AA) by ethnicity and type 2 diabetes (T2D) status. Methods A cross-sectional study in 197 HA (92 with T2D and 102 without T2D) and 200 AA (97 with T2D and 103 without T2D) recruited in South Florida. Serum 25(OH)D concentrations and adipokines were analyzed by ELISA and cardiometabolic risk factors were indexed by obesity, glycemic control, insulin sensitivity, lipid profile, and blood pressure. Results Controlling for age, BMI, energy intake, smoking status and HOMA2-IR in multivariate linear regression analyses, serum 25(OH)D concentrations were significantly associated with WC (R2 = 0.760, B = − 0.092, P = 0.027), HbA1C (R2 = 0.142, B = − 0.012, P = 0.010), and TG (R2 = 0.159, B = − 1.192, P = 0.003) in only HA without T2D. While serum 25(OH)D concentrations were significantly associated with TC (R2 = 0.168, B = − 0.329, P = 0.040), log leptin (R2 = 0.544, B = − 0.007, P = 0.021), and adiponectin (R2 = 0.144, B = 0.111, P = 0.033), but slightly associated with LDL-c (R2 = 0.133, B = − 0.278, P = 0.064) in only AA without T2D. Among individuals with T2D, serum 25(OH)D concentrations were marginally associated with IL-6 (R2 = 0.109, B = 0.076, P = 0.085) in HA with T2D, and there was a trend toward significance with log leptin (R2 = 0.393, B = − 0.006, P = 0.075) in AA with T2D in regression analysis. Conclusions The findings that the associations of serum 25(OH)D concentrations with adipokines and cardiometabolic factors differ between HA and AA has clinical and public implications to guide design of T2D preventive strategies that are culturally specific even within the same ethnicity

Lumbar lordosis in osteoporosis and in osteoarthritis

The curvature of the lumbar spine and the risk of developing either osteoporosis (OP) or osteoarthritis (OA) are influenced by many common factors. The aim of this study is to determine whether lumbar lordosis is different between patients with either disease and healthy persons. A cross-sectional, blinded, controlled design was implemented. One hundred and twelve postmenopausal women were evaluated for bone mineral density as well as undergoing spinal radiography. Lordosis measurement was performed with Cobb’s method. The sample was divided in four groups: patients with OP (n = 34, L1–L5 = 40.7°, L1–S1 = 54.1°), patients with OA (n = 29, L1–L5 = 38°, L1–S1 = 52.3°), patients with both diseases (n = 20, L1–L5 = 41.8°, L1–S1 = 52.3°) and controls (n = 29, L1–L5 = 38.6°, L1–S1 = 51.8°). For all participants age, height, weight, body mass index, physical activity level and basal metabolic rate were measured and recorded. The results revealed that although the four groups have significant constitutional differences, lumbar lordosis was comparable between them. The reasons for the lack of association are discussed