Relationship between body habitus and joint leptin levels in a knee osteoarthritis population

Synovial fluid (SF) leptin has been shown to have an association with cartilage degeneration. Our objective was to examine the relationship between different measures of body habitus and SF leptin levels in an end‐stage knee osteoarthritis (OA) population. Sixty consecutive patients with knee OA were surveyed prior to surgery for demographic data. Body habitus was assessed with the body mass index (BMI), waist circumference (WC), and waist–hip ratio (WHR). SF and serum samples were analyzed for leptin and adiponectin using specific ELISA. Nonparametric correlations and linear regression modeling was used to identify the relationship between the measures of body habitus and SF leptin levels. Females had greater levels of leptin than males in both the serum and SF. Significant correlations were found between SF leptin levels and BMI and WC (R² 0.44 and 0.38, respectively; p < 0.05). Regression modeling showed that female gender and WC were independent predictors of a greater SF leptin level independent of age, BMI, and presence of diabetes (p < 0.05). WC may be a more accurate measure of body habitus than BMI in the relationship between the metabolic effects of adipose tissue and OA. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:329–333, 2010     

Effects of chronic estrogen treatment on modulating age‐related bone loss in female mice

While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age‐related bone loss, we sham‐operated, ovariectomized, or ovariectomized and estrogen‐replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin–) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six‐month‐old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham‐operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen‐treated mice did not prevent age‐related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age‐related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham‐operated mice. As compared with cells from young mice, lin– cells from aged/sham‐operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age‐related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. © 2010 American Society for Bone and Mineral Research.     

Impact of Tibial Tubercle Osteotomy on Final Outcome in Revision Total Knee Arthroplasty: Our Experience and Technique in Pakistan

BackgroudDue to extensive fibrosis during revision surgery, adequate exposure is essential and it can be achieved with several extensile approach options, such as tibial tubercle osteotomy. Information regarding surgical exposure during revision arthroplasty is limited in developing countries, such as Pakistan, due to the lack of adequate data collection and follow-up. Therefore, the purpose of this study was to evaluate the impact of tibial tubercle osteotomy on final outcome of revision total knee arthroplasty (TKA).MethodsA total of 231 revision TKAs were performed between January 2008 and December 2017. Twenty-nine patients underwent tibial tubercle osteotomy for adequate exposure during revision surgery. Of these, 27 patients with complete follow-up were included in our study. Factors examined include age at the time of revision surgery, gender, comorbidities, arthroplasty site (right or left), body mass index (BMI), and primary indications for the tibial tubercle osteotomy during revision TKA. Functional outcome was measured by using Knee Society score (KSS) at 3 months and the final follow-up. All statistical analysis was done using SPSS version 20.0 with a p-value < 0.05 considered significant.ResultsOut of 27 patients, 6 patients (22.2%) were men and 21 patients (77.7%) were women. Right knee revision arthroplasty was performed in 15 patients (55.5%), left knee revision arthroplasty was performed in 12 patients (44.4%), and bilateral revision surgery was performed in only 1 patient (3.7%). The mean BMI was 29.2 kg/m². We used a constrained condylar knee in 20 patients (74%), a rotating hinge knee in 5 patients (18.5%), and mobile bearing tray plus metaphyseal sleeves in 2 patients (7.4%). The KSS was 52.21 ± 4.05 preoperatively, and 79.42 ± 2.2 and 80.12 ± 1.33 at 3 months and 12 months, respectively. Radiological union was achieved in all patients at 3 months. Of 27 patients, only 1 patient (3.7%) had proximal migration of the osteotomy site at 6 months: the patient was asymptomatic and union was also achieved and, therefore, no surgical intervention was performed.ConclusionsTibial tubercle osteotomy during revision TKA can be a safe and reliable technique with superior outcomes and minimal complication rates.     

Delphinidin,a dietary antioxidant,induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three‐dimensional epidermal equivalent models

Delphinidin (Del), [3,5,7,3'‐,4'‐,5'‐hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three‐dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10–40 μm ; 24–48 h) significantly enhanced keratinocyte differentiation. In Del‐treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase‐14 and transglutaminase‐1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis‐related proteins including Bcl‐2 family of proteins and poly(ADP‐ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase‐14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses.     

Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin

Keloid disease (KD) is a fibroproliferative disorder characterised partly by an altered extracellular matrix (ECM) profile. In fetal scarring, hyaluronic acid (HA) expression is increased, but is reduced in KD tissue compared with normal skin (NS). The expression of Hyaluronan Synthase (HAS) and hyaluronidase (HYAL) in KD and NS tissue were investigated for the first time using a range of techniques. Hyaluronan synthase and HYAL mRNA expression were significantly increased in NS tissue compared with KD tissue (P < 0.05). Immunohistological analysis of tissue indicated an accumulation of HAS and HYAL protein expression in KD compared with NS due to the thicker epidermis. No differences were observed in mRNA or protein expression in KD and NS fibroblasts. Reduced expression of HAS and HYAL may alter HA synthesis, degradation and accumulation in KD. Better understanding of the role of HA in KD may lead to novel therapeutic approaches to address the resulting ECM imbalance.     

Functional vision with bilateral ReZoom and ReSTOR intraocular lenses 6 months after cataract surgery

PURPOSE: To compare the visual outcomes in patients with bilateral implantation of AcrySof ReSTOR multifocal intraocular lenses (IOLs) (Alcon Laboratories) or ReZoom multifocal IOLs (Advanced Medical Optics) 6 months after cataract surgery. SETTING: Orsett and Southend Hospital, Essex, United Kingdom. METHODS: This study comprised patients who had uneventful bilateral cataract extraction with implantation of ReZoom (n = 50) or ReSTOR (n = 50) multifocal IOLs. Parameters analyzed included binocular uncorrected distance, intermediate, and near acuities; spectacle independence; subjective visual symptoms; and patient satisfaction. All parameters were evaluated 6 months after second-eye surgery. RESULTS: All patients had binocular uncorrected distance visual acuity of 20/32 or better; there was no statistically significant difference between the 2 groups. The mean binocular uncorrected near acuity was 20/26 (J1.22) in the ReSTOR group and 20/34 (J2.34) in the ReZoom group (P<.0001). The mean binocular uncorrected intermediate visual acuity was 20/42 and 20/34, respectively (P = .003). Patients in the ReZoom group reported greater satisfaction with intermediate vision (P = .04). No statistically significant difference was found in satisfaction with near vision. Eighty-six percent of ReSTOR patients and 70% of ReZoom patients did not wear glasses for daily activities; the overall satisfaction was not statistically significantly different between groups. There was no significant difference between groups in photic phenomena. CONCLUSIONS: The ReSTOR IOL provided better near vision and the ReZoom IOL better intermediate vision. Both multifocal IOLs gave excellent distance vision. Photic phenomena were comparable and clinically acceptable. ReSTOR patients had greater spectacle independence for near vision and ReZoom patients for intermediate vision. Overall spectacle independence was not statistically significantly different.     

The effects of perinatal hypoxia on the behavioral,neurochemical, and neurohistological toxicity of the metabolic inhibitor 3-nitropropionic acid

3-nitropropionic acid (3-NPA) neurotoxicity and long-term effects of perinatal hypoxia were evaluated in 18 adult rats. Hypoxia-insulted (I) and noninsulted (NI) rats were delivered by cesarean section. Hypoxic insult was effected by submerging dissected uterine horns in warmed saline for 15 min. NI rats were delivered from the adjacent nonsubmerged horns. At postnatal day 90, I and NI rats were trained to perform tasks thought to measure behaviors dependent upon aspects of time estimation (TE), motivation, and learning. At 12 months of age, rats were injected i.p. with escalating doses of 3-NPA (5 mg/kg/day to a maximum of 30 mg/kg/day) immediately after each test session and sacrificed at the end of treatment. Additional male rats were used as untreated controls. Although 3-NPA produced a dose-dependent impairment of performance in each task, the effects were qualitatively similar for each group. A significant difference between I and NI rats was, however, observed in the TE task where NI rats completed less of the task at high doses of 3-NPA compared to I rats. Compared to untreated controls, dopamine concentrations were decreased in caudate nucleus of both I and NI rats after 3-NPA. Specific areas most frequently damaged included cerebral cortex, hippocampal subfield CA1, thalamus, caudate nucleus, and the cerebellum. Lesions usually were less extensive in the I rather than NI members of a littermate pair, suggesting a possible protective effect of perinatal hypoxia against subsequent 3-NPA neurotoxicity.