Metabolic vs. hedonic obesity: a conceptual distinction and its clinical implications.

Body weight is determined via both metabolic and hedonic mechanisms. Metabolic regulation of body weight centres around the 'body weight set point', which is programmed by energy balance circuitry in the hypothalamus and other specific brain regions. The metabolic body weight set point has a genetic basis, but exposure to an obesogenic environment may elicit allostatic responses and upward drift of the set point, leading to a higher maintained body weight. However, an elevated steady-state body weight may also be achieved without an alteration of the metabolic set point, via sustained hedonic over-eating, which is governed by the reward system of the brain and can override homeostatic metabolic signals. While hedonic signals are potent influences in determining food intake, metabolic regulation involves the active control of both food intake and energy expenditure. When overweight is due to elevation of the metabolic set point ('metabolic obesity'), energy expenditure theoretically falls onto the standard energy-mass regression line. In contrast, when a steady-state weight is above the metabolic set point due to hedonic over-eating ('hedonic obesity'), a persistent compensatory increase in energy expenditure per unit metabolic mass may be demonstrable. Recognition of the two types of obesity may lead to more effective treatment and prevention of obesity.

Randomized pilot study of cabergoline, a dopamine receptor agonist: effects on body weight and glucose tolerance in obese adults.

AIM: Dopaminergic hypofunction and hyperprolactinaemia have been implicated in the pathogenesis of obesity and glucose intolerance. The aim of this pilot study was to determine the efficacy of cabergoline, a dopamine receptor agonist, on body weight and glucose tolerance in obese non-diabetic persons with normal plasma prolactin levels. METHODS: This 16-week double blind, placebo-controlled pilot study randomized non-diabetic obese adults (body mass index 30-42 kg/m(2) ) to placebo or cabergoline (0.25 mg twice weekly for 4 weeks followed by 0.5 mg twice weekly for the next 12 weeks). Of 40 subjects enrolled, 29 completed 16 weeks: 16 randomized to placebo and 13 to cabergoline. All subjects were counselled on a 500 kcal/day calorie deficit diet. A 75-g oral glucose tolerance test was performed at baseline and at 16 weeks. RESULTS: As expected, prolactin levels decreased after cabergoline (p < 0.001). Weight loss was similar after placebo compared with cabergoline treatment: 1.0 vs. 1.2% body weight, respectively. Fasting glucose levels did not differ between groups after treatment, however, 90-min postprandial glucose and insulin decreased in the cabergoline group only (p = 0.029). HOMA-IR (homeostasis model of assessment) increased by 40% after placebo and 1.5% after cabergoline treatment. CONCLUSIONS: This pilot study suggests that cabergoline therapy may improve glucose tolerance independent of weight loss, however, a larger, longer term study of dopamine receptor agonist therapy in obese individuals is warranted to confirm this finding.

Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass.

OBJECTIVE: The objective of this study was to quantify hormones that regulate energy and glucose homeostasis to establish possible mechanisms for the greater efficacy of Roux-en-Y gastric bypass (RYGB) compared with laparoscopic adjustable gastric banding (LAGB) in achieving weight loss and improved insulin sensitivity. DESIGN: Longitudinal study of patients undergoing LAGB (n=15) and RYGB (n=28) who were studied before surgery and at 2, 12, 26 and 52 weeks afterwards. MEASUREMENTS: Fasting blood samples were drawn at each visit. Postprandial blood samples were also obtained before surgery and at 26 and 52 weeks. Samples were assayed for peptide YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, leptin, thyrotropic hormone, free T(4) and free T(3). RESULTS: At 1 year there was greater weight loss in RYGB compared with LAGB patients (30 vs 15%), but final body mass index was similar (34 vs 33 kg m(-2)). At week 52, area under the curve (AUC) for PYY in RYGB subjects was greater than LAGB (P<0.01). GLP-1 levels at 30 min after meal were threefold greater after RYGB compared with LAGB (P<0.001). Conversely, ghrelin AUC increased after LAGB at week 52 (P<0.05) but tended to decrease after RYGB. Fasting glucose, insulin, and leptin and homeostasis model of assessment (HOMA-IR) decreased in both groups over time but were significantly lower at week 52 after RYGB compared with LAGB. The change in leptin correlated significantly with weight loss in LAGB (r=0.86) and RYGB (r=0.77), however, HOMA-IR correlated significantly with weight loss only in LAGB (r=0.78), and not RYGB (r=0.15). There was a significant decrease in free T(3) (P<0.01) after RYGB. CONCLUSIONS: Differences in levels of gut hormones may play a role in promoting greater weight loss and insulin sensitivity after RYGB compared with LAGB, however, weight loss may be limited by decreases in free T(3) and leptin.

Sex differences in visceral adipose tissue post-bariatric surgery compared to matched non-surgical controls.

OBJECTIVE AND METHODS: Given the profound weight loss after gastric banding and bypass we compared fat compartmentalization by whole body magnetic resonance imaging in women and men after these procedures to two groups of non-surgical controls who were either matched for age, weight and height or were of lower body mass index (BMI). RESULT: In women post-surgery (n=17; BMI 31.7 kg/m(2)) there was lower visceral adipose tissue (VAT) (1.4 vs 2.5 kg; P<0.01) compared with matched controls (n=59; BMI 32.1 kg/m(2)). In contrast, VAT (5.3 vs 5.4 kg) was nearly identical in men post-surgery (n=10; BMI 34.1 kg/m(2)) compared with matched controls (n=10; BMI 32.1 kg/m(2)) even though the degree of weight reduction was not significantly different from women (27.4 vs 32.6%). Furthermore, VAT when adjusted for total adipose tissue (TAT) was 43% less in women post-surgery (1.2 vs 2.1 kg; P=0.03) than in controls with lower BMI (25.1 kg/m(2)). After adjustment for TAT, subcutaneous adipose tissue in women post-surgery was significantly greater than matched controls (35.1 vs 34.2 kg; P=0.03). There was a significant negative correlation of VAT and the degree of weight loss in women (r=-0.57; P=0.018) but this relationship was not significant in men (r=-0.39; P=0.27). Skeletal muscle was lower in both sexes compared with matched controls (women, 21.8 vs 23.1 kg; men, 32.5 vs 35.5 kg). CONCLUSION: Prospective studies are necessary to confirm if there is a sexual dimorphism in the effects of bariatric surgery on body composition.

Genetic deletion of JNK1 and JNK2 aggravates the DSS-induced colitis in mice.

The c-Jun N-terminal kinases (JNKs) are considered as novel targets for therapy of inflammatory bowel diseases (IBD). However, the relevant JNK isoforms have to be elucidated. Here, we analyze the individual contribution of the JNK1 and JNK2 isoforms in a dextran sulfate sodium (DSS) model of experimental colitis. JNK1 and JNK2 knockout mice (JNK1 ko, JNK2 ko) and their wild-type controls (WT1, WT2) received three cycles of DSS treatment, each consisting of 1.7% DSS for 5 days, followed by 5 days with water. Animals were daily evaluated by a disease activity index (DAI) comprising measurement of body weight, estimation of stool consistency, and test for occult blood/gross rectal bleeding. After 30 days all animals were sacrificed, and the inflamed intestine was histologically evaluated by a crypt damage score. Unexpectedly, neither JNK1 ko nor JNK2 ko prevented mice from developing a chronic colitis when compared to wild-type controls WT1 and WT2, respectively. On the contrary, DAI and mortality were aggravated in JNK2 ko compared to WT2. DAI and mortality did not differ between JNK1 ko and WT1, but the histological crypt damage score was significantly enhanced in the cecum of JNK1 ko mice. Genetic deletion of JNK2 worsens the disease outcome in an experimental model of murine colitis. We hypothesize that the functional deletion of the otherwise proapoptotic JNK2 prolongs the activity of proinflammatory immune cells with deterioration of disease activity.

The influence of bone allograft processing on osteoblast attachment and function.

In order to assess the influence of eight different sterilisation and disinfection methods for bone allografts on adhesion, proliferation, and differentiation of human bone marrow stromal cells (BMSC), cells were grown in culture and then plated onto pieces of human bone allografts. Following processing methods were tested: autoclavation (AUT), low-temperature-plasma sterilisation of demineralised allografts (D-LTP), ethylene oxide sterilisation (EtO), fresh frozen bone (FFB), 80 degrees C-thermodisinfection (80 degrees C), gamma-irradiation (Gamma), chemical solvent disinfection (CSD), and Barrycidal-disinfection (BAR). The seeding efficiency was determined after one hour to detect the number of attached cells before mitosis started. The cell viability was determined after 3, 7, and 21 days. Tests to confirm the osteoblastic differentiation included histochemical alkaline phosphatase staining and RT-PCR for osteocalcin. Human BMSC showed greatest attachment affinities for D-LTP-, 80 degrees C-, and CSD-allografts, whereas less cells were found attached to AUT-, EtO-, FFB-, Gamma-, and BAR-probes. Cell viability assays at day 3 revealed highest proliferation rates within the FFB- and 80 degrees C-groups, whereas after 21 days most viable cells were found in D-LTP-, 80 degrees C-, CSD-, and Gamma-groups. BAR-treatment showed a considerably toxic effect and therefore was excluded from all further experiments. Highest AP-activity and gene expression of osteocalcin were detected in the D-LTP-group in comparison with all other groups. In summary, our results demonstrate that cell adhesion, final population, and function of BMSC are influenced by different disinfection and sterilisation methods. Therefore, processing-related alterations of BMSC-function may be important for the success of bone grafting. The experimental setup used in the present work may be useful for further optimisation of bone allograft processing.

[Surgical treatment of type I capitellar-humeral fractures using the Henry ventral approach approach. Short- and medium-term results]. / Operative Versorgung von Capitulum-humeri-Typ-I-Frakturen über den ventralen Zugang nach Henry Kurz- und mittelfristige Ergebnisse.

Capitellar fractures are rare. Despite adequate surgical treatment, patients suffer frequently from limited range of motion, osteonecrosis, and neurological deficits. The purpose of this retrospective study was to evaluate short- and medium-term surgical results in seven patients who had type I capitellar fractures according to Bryan and Morrey. All patients were treated via an anterior approach, according to Henry, and open reduction and internal fixation with two screws. Seven patients were examined clinically, neurologically, and radiologically after 10-65 months. The fracture healed in all patients. None of the patients had a neurological deficit. According to the Morrey Score, five of seven patients had an excellent or good functional result. Open reduction and internal fixation with two screws via the Henry approach is a suitable option for surgical treatment for type I capitellar fractures.

[Monteggia injuries in adults: Critical analysis of injury pattern, management, and results]. / Monteggia-Verletzungen im ErwachsenenalterEine kritische Analyse von Verletzungsmuster, Management und Ergebnissen.

BACKGROUND: Complications, revision surgery, and unsatisfactory functional results after operative management of Monteggia fractures are frequent. Moreover, hardly any studies exist that deal exclusively with the therapeutic concept for adults. PATIENTS AND METHODS: Between January 1988 and December 2001, 68 patients with Monteggia fractures or equivalent injury were surgically treated. A total of 49 patients could be followed up after 83 months (25-176). Fracture type was assessed according to Bado's classification, functional results according to the Mayo elbow performance score, and the extent of osteoarthritis based on the criteria of Baird and Johnson. RESULTS: The median age of the follow-up patients was 38 years (18-89, 31 men, 18 women). Corresponding to Bado's classification the following injuries were observed: 18 cases of type 1, 22 of type 2, 5 of type 3, and 4 cases of type 4. After surgical intervention, 14 patients achieved "very good", 21 "good", 9 "satisfactory", and 5 "poor" results. Of the 14 patients with either "satisfactory" or "poor" results, 9 manifested a type 2 injury. Complications requiring revision surgery occurred in 14 patients and complications not requiring revision in another 14. Severe osteoarthritic changes in the humeral or radioulnar joint were observed in 4 cases. CONCLUSIONS: Monteggia fractures in adults are fraught with complications despite good functional results in the majority of cases. The patient should be made aware early on of the risk of residual functional deficits and the need for further surgical intervention.

[Are angle-fixed implants with elastic properties advantageous for the internal fixation of proximal humerus fractures?]. / Sind winkelstabile Plattensysteme mit elastischen Eigenschaften für die Stabilisierung der Oberarmkopffraktur vorteilhaft? Eine in-vitro biomechanische Untersuchung.

There is a recent interest for the use of angle-fixed plates in the management of proximal humerus fractures. Rigid implants might be associated with an increased risk of cutting-out. In order to analyse the potential beneficial effects of the implant elasticity on fracture fixation, the biomechanical properties of a rigid and an elastic angle-fixed plating system were assessed in an experimental study. An unstable fracture of the surgical neck was created in 8 pairs of human humeri. Specimens were subjected to axial loading and torque. Stiffness, subsidence and load to failure were assessed. The implant with elastic properties was characterized by a lower torsional stiffness and a higher subsidence during axial loading and torque. This implant failed at lower loads than the rigid implant did. Elastic implant properties of angle-fixed plates have shown not to be advantageous for the management of fractures of the proximal humerus.

Effects of agouti-related protein on metabolism and hypothalamic neuropeptide gene expression.

The hypothalamic melanocortin system regulates feeding in part through interaction of the appetite stimulating peptide, agouti-related protein (AGRP), and the anorectic peptide, alpha-melanocyte stimulating hormone, a peptide derived from the pro-opiomelanocortin (POMC) polyprotein. Central administration of AGRP induces hyperphagia and increased gain in body weight in rodents, but may also exert metabolic effects even when hyperphagia is prevented. In the present studies, the effects of AGRP on hypothalamic neuropeptide gene expression and metabolism were examined in the rat. Central administration of AGRP for 3- and 7-day periods resulted in hyperphagia, increased body weight and increased plasma leptin and insulin concentrations compared to saline-injected controls. Hypothalamic concentrations of Pomc mRNA were also increased by 27% and 44% (in 3- and 7-day experiments, respectively). The hypothalamic concentration of Agrp mRNA was unchanged after 3 days, but was significantly decreased by 33% after 7 days of AGRP infusion. To determine if these changes were dependent upon AGRP-induced hyperphagia, pair-fed rats with restricted food intake receiving central administration of AGRP were also studied. In the absence of hyperphagia, intracerebralventricular administration of AGRP caused significant increases in plasma leptin and insulin concentrations (two-fold and 1.5-fold, respectively) and fat pad mass. A significant increase in hypothalamic Pomc mRNA concentrations was not detected in pair-fed rats. In contrast, Agrp mRNA concentrations remained suppressed by 45% in the pair-fed group after 7 days of AGRP infusion despite equal body weight compared to saline controls. The ratio of hypothalamic Pomc to Agrp mRNA was elevated two-fold in ad libitum and pair-fed AGRP-injected rats, which is consistent with increased stimulation of central melanocortin signalling pathways. Thus, central administration of AGRP exerts changes in hypothalamic neuropeptide gene expression and metabolic effects that are independent of the effects on food intake and body weight.

B0-B(-)0 mixing beyond factorization in QCD sum rules.

We present a calculation of the B0-B(-)0 mixing matrix element in the framework of QCD sum rules for three-point functions. We compute alpha(s) corrections to a three-point function at the three-loop level in QCD perturbation theory, which allows one to extract the matrix element with next-to-leading order (NLO) accuracy. This calculation is imperative for a consistent evaluation of experimentally measured mixing parameters since the coefficient functions of the effective Hamiltonian for B0-B(-)0 mixing are known at NLO. We find that radiative corrections violate factorization at NLO; this violation is under full control and amounts to 10%. The resulting value of the B parameter is found to be B(B)(m(b))=1+0.1(PT)-0.05(non-PT).

Proximal humeral fractures: how stiff should an implant be? A comparative mechanical study with new implants in human specimens.

BACKGROUND: The objective of this study was to determine the in vitro characteristics of the clinically used and newly developed implants for the stabilization of proximal humeral fractures under static and cyclic loading. The goal was to optimize implant stiffness for fracture stabilization even in weak bone stock. METHODS: In a laboratory study using 35 fresh human humeri, the specimens were randomized into 5 groups, which included the clinically used humerus T-plate (HTP), the cross-screw osteosynthesis (CSO), the unreamed proximal humerus nail with spiral blade (UHN), the recently developed Synclaw Proximal Humerus Nail (Synclaw PHN) and the angle-stable Locking Compression Plate Proximal Humerus (LCP-PH). The implant stiffness was determined for three clinically relevant load cases: axial compression, torsion and varus bending. In addition, a cyclic varus-bending test was performed to determine the implant properties under cyclic loading. RESULTS: In contrast to a rather elastic and minimally invasive implant(LCP-PH), the conventionally designed ones (Synclaw PHN, CSO, HTP, UHN) showed rather high stiffness values under static loading. In cyclic loading, a strong decrease in stiffness ( p<0.05) was found for the rigid implants HTP and UHN. In comparison with the other implants, only the elastic implant (LCP-PH) showed a significantly lower load reduction in a weak bone stock (17+/-6.2%). CONCLUSION: The high initial stiffness of rigid implants led to an early loosening and failure of the implant-bone interface under cyclic loading. Implants with low stiffness and elastic characteristics, however, appear to minimize the peak stresses at the bone-implant interface, making them particularly suitable for fracture fixation in osteoporotic bone.

[Tibial plateau fracture--biodegradable bonecement-augmentation]. / Tibiakopfplateaufrakturen--Erste Erfahrungen mit einem resorbierbaren Knochenzement zur Augmentation.

Between October 1996 and January 1999,29 patients (f:16,m:13,age: 22-86) with fractures of the lateral tibial plateau were operated on arthroscopic,fluoroscopic control or were treated with open reduction and internal fixation. 15 of them were retrospective and 14 prospective analysed. The metaphyseal defect after elevation of the depressed fragment was augmented in 11 cases with autologous spongeous bone grafting,in 9 cases with biodegradable bone cement (Norian SRS). Augmentation was unnecessary in 9 cases. The results according to the Lysholm score and the radiological results were good or excellent. Concerning the kind of augmentation no difference was noted. In the Norian SRS-group the duration of postoperative treatment was shorter than in the other group. The duration of partial weight bearing was shorter too. The results of the present study suggest that an injectable calcium phosphate cement may be a competent material for augmentation in lateral tibial plateau fractures because of the application form and the initial high mechanical stability.

[Age- and gender-related distribution of bone mineral density and mechanical properties of the proximal humerus]. / Alters- und geschlechtsabhängige Knochenmineraldichteverteilung und mechanische Eigenschaften des proximalen Humerus.

PURPOSE: To evaluate age- and gender-related mechanical properties and bone mineral density (BMD) of the proximal humerus at different levels and regions. MATERIALS AND METHODS: Mechanical indentation testing, DXA, QCT, pQCT and the radiogrammetry (Cortical Index, CI) were carried out in 70 freshly harvested humeri from 46 human cadavers (23 females, 23-males; median age 70.5 years). RESULTS: In the female group, a high correlation between age and BMD was found (rho = 0.62 to -0.70, p < 0.01) with statistically significant differences between specimens of patients 69 years or younger, and 70 years or older (p < 0.05). In the group of female specimens of age 70 years or older, BMD values were found to be significantly lower compared to their male counterparts (p < 0.05). Regardless of the specimen's age, the highest BMD and bone strength were found in the proximal aspect and in the medial and dorsal regions of the proximal humerus. CONCLUSION: These findings provide an insight into the fracture mechanism of the proximal humerus and should be the basis for designing structure-oriented implants with improved implant-bone stability in osteoporotic patients.

[Isolated rupture of the subscapularis tendon in the overhead athlete - the result of chronical overuse?]. / Die isolierte Ruptur der Subskapularissehne beim jungen Uberkopfsportler - Folge chronischer Uberbeanspruchung?

The case of a 27-year-old overhead athlete with chronic shoulder pain because of an isolated subscapularis tear without trauma is described. Arthroscopy has proven to be the appropriate method for detailed visualisation of the injury and facilitates the operative planning. Furthermore, arthroscopy closes the problem of a "diagnostic gap". In the presented case, the results at the two year follow-up are excellent. The authors conclude that an operative approach is also justified in non-traumatic isolated ruptures of the subscapularis muscle.

Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus.

Agouti-related protein (AGRP) is synthesized in the same neurones in the arcuate nucleus as neuropeptide Y (NPY), another potent orexigenic peptide. AGRP antagonizes the action of alpha-melanocyte stimulating hormone, a derivative of pro-opiomelanocortin (POMC) at the hypothalamic MC4 receptor to increase food intake. Although leptin has been shown to regulate Agrp/Npy and Pomc-expressing neurones, there are differences with respect to Agrp regulation in leptin receptor-deficient mice and rats. Unlike the obese leptin receptor-deficient db/db mouse, which exhibits upregulation of Agrp mRNA expression in the medial basal hypothalamus (MBH) compared to lean controls, the obese leptin receptor-deficient (faf; Koletsky) rat does not exhibit upregulation of Agrp expression. To determine whether this represents a general difference between leptin receptor-deficient mice and rats, neuropeptide gene expression was analysed in the MBH of lean and obese rats segregating for a different leptin receptor mutation, Leprfa (Zucker). Fasting in lean rats (+/fa) for 72 h significantly increased Agrp and Npy mRNA expression, and decreased Pomc mRNA expression as detected by a sensitive solution hybridization/S1 nuclease protection assay. Npy mRNA levels were significantly increased in fed obese fa/fa compared to lean rats, and further increased in the obese animals after fasting. In contrast, Agrp mRNA levels did not differ between fed lean and fed obese rats, and fasting did not significantly change Agrp levels in obese rats. To determine whether the change in Agrp expression that occurs with food deprivation in lean rats could be prevented by leptin replacement, Sprague-Dawley rats were fasted and infused via subcutaneous osmotic micropumps for 48 h with either saline or recombinant mouse leptin. Fasting significantly increased Agrp and Npy, and decreased Pomc mRNA levels. Leptin infusion almost completely reversed these changes such that there was no significant difference between the levels in the fasted rats and those that were fed ad libitum. Thus, in fasted lean rats, Agrp and Npy are upregulated in parallel when leptin levels fall and are downregulated by leptin infusion. By contrast, the absence of a functional leptin receptor results in the upregulation of Npy but not Agrp mRNA.

Arthroscopic-assisted simultaneous reconstruction of the posterior cruciate ligament and the lateral collateral ligament using hamstrings and absorbable screws.

Arthroscopic-assisted simultaneous reconstruction of the posterior cruciate ligament (PCL) and the lateral collateral ligament (LCL) using hamstring tendon grafts is described. The femoral tunnel is drilled through an incision over the medial femoral condyle and the tibial tunnel through the same skin incision used for harvesting the tendon graft. PCL reconstruction is performed using a 4-strand hamstring tendon graft and absorbable screw fixation. The tendon of the semitendinosus muscle of the uninvolved knee is used as a lateral loop for LCL reconstruction. After pulling the transplant through the fibular head, femoral fixation of the loop is made with an absorbable screw.

[Crossed screw osteosynthesis of proximal humerus fractures]. / Die gekreuzte Schraubenosteosynthese proximaler Humerusfrakturen.

Between March 1997 and October 1999 thirty-one patients with displaced proximal humeral fractures were treated with crossed screw osteosynthesis. Insertion of the screws was realized by using a deltoideo-pectoral approach placing the screws anteriorly and posteriorly in a crossed manner from the distal fragment into the humeral head. Additionally, in all two-part-fractures a tension band was applied. In all three-part-fractures, the greater tuberosity was reattached by additional screws. In 21 patients (14 female, 7 male, median age 62 years, 18-86) a clinical and radiological follow-up (median 18 months, 10-29) was obtained. Fractures were classified as two-part-fractures in 10 patients and as three-part-fractures in 11 patients. According to the Constant-Score, "excellent" and "good" results were achieved in 15 patients, "moderate" results were found in 3 patients. However, in 3 patients results were only "poor" (1 two-part-, 2 three-part-fractures). The complication rate was 29% (premature hardware removal due to head perforation in 3 cases; humeral head necrosis necessitating prosthetic replacement in 2 patients; secondary displacement in 1 case). Crossed screw osteosynthesis represents an justified alternative in the surgical treatment of displaced proximal humeral fractures permitting early functional therapy.

HPLC evaluation of diclofenac in transdermal therapeutic preparations.

High-performance liquid chromatography (HPLC) was selected for analytical evaluation of sodium diclofenac in original transdermal therapeutic preparations containing adjuvant substances (capsaicin, hyoscyamine). After isolation from laminated adhesive patches, diclofenac was analysed on columns with reversed phase, using the mobile phase ethanol and phosphate buffer (pH 6.5) with an addition of tetrabutylammonium iodide and detection at 284 nm. Not only the total amount of diclofenac in the patch was evaluated, but HPLC methodology was also employed to select a suitable acceptor medium for permeation experiments. In patches manufactured in the tested series, HPLC was also employed to examine the release of diclofenac and its in vitro permeation through the human skin.

An update on the science and therapy of obesity and its relationship to osteoarthritis.

Obesity and osteoarthritis are two commonly encountered clinical problems that can lead to significant physical and emotional disability. This report examines the association between obesity and osteoarthritis, and discusses potential mechanisms by which obesity influences osteoarthritis. Special attention is devoted to reviewing the molecular and genetic mechanisms that underlie the development of clinical obesity. Improved understanding of obesity will hopefully lead to improved treatment and subsequent amelioration of this important risk factor for osteoarthritis.