Development of the Revision Hip Complexity Classification using a modified Delphi technique.

AIMS: The aim of this modified Delphi process was to create a structured Revision Hip Complexity Classification (RHCC) which can be used as a tool to help direct multidisciplinary team (MDT) discussions of complex cases in local or regional revision networks. METHODS: The RHCC was developed with the help of a steering group and an invitation through the British Hip Society (BHS) to members to apply, forming an expert panel of 35. We ran a mixed-method modified Delphi process (three rounds of questionnaires and one virtual meeting). Round 1 consisted of identifying the factors that govern the decision-making and complexities, with weighting given to factors considered most important by experts. Participants were asked to identify classification systems where relevant. Rounds 2 and 3 focused on grouping each factor into H1, H2, or H3, creating a hierarchy of complexity. This was followed by a virtual meeting in an attempt to achieve consensus on the factors which had not achieved consensus in preceding rounds. RESULTS: The expert group achieved strong consensus in 32 out of 36 factors following the Delphi process. The RHCC used the existing Paprosky (acetabulum and femur), Unified Classification System, and American Society of Anesthesiologists (ASA) classification systems. Patients with ASA grade III/IV are recognized with a qualifier of an asterisk added to the final classification. The classification has good intraobserver and interobserver reliability with Kappa values of 0.88 to 0.92 and 0.77 to 0.85, respectively. CONCLUSION: The RHCC has been developed through a modified Delphi technique. RHCC will provide a framework to allow discussion of complex cases as part of a local or regional hip revision MDT. We believe that adoption of the RHCC will provide a comprehensive and reproducible method to describe each patient's case with regard to surgical complexity, in addition to medical comorbidities that may influence their management. Cite this article: Bone Jt Open 2022;3(5):423-431.

SGLT2 Inhibitors: Benefits for CKD and Cardiovascular Disease in Type 2 Diabetes.

PURPOSE OF REVIEW: Over the past few decades, multiple glucose lowering therapies have been developed, but until now, no single drug has proven to both decrease cardiovascular mortality and improve renal outcomes. The purpose of this review is to outline the key findings of the recent major outcome clinical trials on SGLT2 inhibitors, review the indications for their use, and improve adoption of these medications in patients with type 2 diabetes mellitus (T2DM). RECENT FINDINGS: Recent studies have shown a benefit for SGLT2 inhibitors in patients with heart failure (HF) and kidney disease both in the presence and absence of T2DM. Additional benefits also include improvements in fluid status, blood pressure, serum uric acid levels, and weight loss. Available data suggests that SGLT2 inhibitors should be used in all eligible patients with HFrEF and/or CKD with albuminuria to decrease progression of CKD, hospitalizations for heart failure, major atherosclerotic cardiovascular events, and cardiovascular death, with and without T2DM.

A Study Comparing the Outcomes of Transverse Ulnar Shortening Osteotomy Fixed with a DCP to Oblique Osteotomy Fixed with a Procedure Specific Plate.

Background: Ulnar shortening osteotomy (USO) is a well-established procedure for ulnar impaction syndrome. Various types of osteotomies have been described. Methods: A retrospective cohort study was conducted to compare the results of transverse osteotomy (TO) fixed with a small fragment dynamic compression plate (Synthes, Pennsylvania, USA), to oblique osteotomy (OO) fixed with a procedure specific plate and instrumentation system (Acumed LLC, Oregon, USA). A total of 39 patients underwent TO and 62 patients underwent OO between 2007 and 2016. The main outcomes compared were rate of union, duration of radiological healing, implant removal rate and other complications. Results: The two groups were comparable with regards to demographics, side operated and smoking status (p > 0.05). Amongst the TO group; 36 out of 39 patients (92.3%) achieved union, 3 patients (7.7%) developed non-union. Six out of the 36 healed TO (16.6%) required removal of hardware due to implant-related pain. No other complications were recorded amongst TO group needing surgical intervention. Amongst the OO group, 2 of the early cohort of 62 patients (3.2%) sustained acute failure of the metalwork due to technical error. One of the remaining 60 patients (1.6%) developed non-union giving an overall union rate of 95.2%. Two patients out of 59 healed OO (3.3%) required removal of hardware. Conclusions: Although there were 2 early failures, there was a trend towards improved union rate with OO, but this did not reach statistical significance (p > 0.05). There was a significantly higher hardware removal rate recorded in TO group (p = 0.023). The OO showed shorter duration for radiological healing than TO (p < 0.05). USO performed with an OO and fixed with procedure specific plate has lower implant removal rate, a shorter duration for radiological healing and comparable union rate to TO fixed with DCP, but needs careful attention to detail.

Cementation technique for elbow arthroplasty; an international survey.

BACKGROUND: Modern cementation techniques have markedly improved survivorship in lower limb arthroplasty, which have been heavily researched in the hip and knee but less so for upper limb procedures. Aseptic loosening is a leading cause of failure in total elbow arthroplasty (TEA) which could be related to the quality of cementation. The aim of this study was to investigate the cementation techniques used for TEA among practicing elbow surgeons. METHODS: An electronic questionnaire was emailed to members of the British elbow and shoulder society (BESS) and PubMed identified experts. Questions focused on the type of prosthesis, operative rates for elective and trauma cases, nature of cement used, canal preparation and cement insertion. Opinions regarding satisfaction with current techniques and mantle quality were also collected. RESULTS: A total of 26 surgeons completed the questionnaire. The Coonrad-Moorey was the most popular device amongst respondents. Most cemented both components, used antibiotic loaded cement, washed the canal with saline and inserted the cement retrograde. There was wide variation in cementation techniques used for the humerus and ulna, particularly regarding cement preparation, insertion, and use of a restrictor and pressurisation. CONCLUSION: Modern cementation techniques are not being utilised in TEA which could be contributing to implant loosening rates and longevity.

EB 2017 Article: Soy protein isolate feeding does not result in reproductive toxicity in the pre-pubertal rat testis.

The isoflavone phytoestrogens found in the soy protein isolate used in soy infant formulas have been shown to have estrogenic actions in the developing male reproductive tract resulting in reproductive toxicity. However, few studies have examined potential estrogenicity of soy protein isolate as opposed to that of pure isoflavones. In this study, we fed weanling male Sprague-Dawley rats a semi-purified diet with casein or soy protein isolate as the sole protein source from postnatal day 21 to 33. Additional groups were fed casein or soy protein isolate and treated s.c. with 10 µg/kg/d estradiol via osmotic minipump. Estradiol treatment reduced testis, prostate weights, and serum androgen concentrations ( P < 0.05). Soy protein isolate had no effect. Estradiol up-regulated 489 and down-regulated 1237 testicular genes >1.5-fold ( P < 0.05). In contrast, soy protein isolate only significantly up-regulated expression of 162 genes and down-regulated 16 genes. The top 30 soy protein isolate-up-regulated genes shared 93% concordance with estradiol up-regulated genes. There was little overlap between soy protein isolate down-regulated genes and those down-regulated by estradiol treatment. Functional annotation analysis revealed significant differences in testicular biological processes affected by estradiol or soy protein isolate. Estradiol had major actions on genes involved in reproductive processes including down-regulation of testicular steroid synthesis and expression of steroid receptor activated receptor (Star) and cytochrome P450 17α-hydroxylase/(Cyp17a1). In contrast, soy protein isolate primarily affected pathways associated with macromolecule modifications including ubiquitination and histone methylation. Our results indicate that rather than acting as a weak estrogen in the developing testis, soy protein isolate appears to act as a selective estrogen receptor modulator with little effect on reproductive processes. Impact statement Soy protein isolate (SPI) is the sole protein used to make soy-based infant formulas. SPI contains phytoestrogens, which are structurally similar to estradiol. These phytoestrogens, daidzein, genistein, and equol, fit the definition of endocrine-disrupting compounds, and at high concentrations, have estrogenic actions resulting in reproductive toxicity in the developing male, when provided as isolated chemicals. However, few animal studies have examined the potential estrogenicity of SPI as opposed to pure isoflavones. In this study, SPI feeding did not elicit an estrogenic response in the testis nor any adverse outcomes including reduced testicular growth, or androgen production during early development in rats when compared to those receiving estradiol. These findings are consistent with emerging data showing no differences in reproductive development in males and female children that received breast milk, cow's milk formula, or soy infant formula during the postnatal feeding period.

Result of IOFIX (Intra Osseous FIXation) device for first metatarsophalangeal joint arthrodesis: A single surgeon's series.

BACKGROUND: Arthrodesis of the first metatarsophalangeal joint (MTPJ) is a common procedure to treat significant first MTPJ arthritis. However, dorsal plates used for this have been associated with high incidence of metalwork removal. The IOFIX (Intra-Osseous FIXation) is a fixed angle device that is noted to provide a more uniform compression over a larger aspect of the fusion surfaces than a screw construct alone with the advantage of minimizing soft tissue irritation which can reduce the need for subsequent implant removal. METHODS: Twenty one consecutive patients who underwent primary first MTPJ fusion with the IOFIX were reviewed. The mean age of the cohort was 63 years (range 47-81), with 80% female. The ratio of left to right was 9:12. The mean follow up of was 28 months (range 13.4-48.2 months). Outcomes analyzed were rate of fusion, Manchester-Oxford foot questionnaire (MOXFQ) score, patient satisfaction, improvement in the intermetatarsal angle and complications. RESULTS: Complete fusion of the first MTPJ was achieved in twenty (95%) patients. One patient had a non union and another patient developed a delayed union. The mean preoperative MOXFQ score improved from 49.7 (95% confidence interval: 46-52) to 17.9 (95% confidence interval: 12-22), p<0.05.Improvement gained in all the domains of the MOXFQ score (walking/standing, pain and social) was statistically significant (p<0.05). Eighteen out of 21 patients (85%) were very pleased or fairly pleased with the procedure. CONCLUSION: Early results show that the rate of fusion achieved by using the IOFIX device for the first MTPJ arthrodesis in our series was found to be comparable to other devices quoted in the literature.

RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17ß-estradiol and casein.

This data file describes the bioinformatics analysis of uterine RNA-seq data comparing genome wide effects of feeding soy protein isolate compared to casein to ovariectomized female rats age 64 days relative to treatment of casein fed rats with 5 µg/kg/d estradiol and relative to rats treated with estradiol and also fed soy protein isolate. Complete raw data files were deposited in the gene Expression Omnibus (GEO) at NCBI (http:/www.ncbi.nlm.nih.gov.geo/) under the GEO accession number GEO: GSE69819. Data presented here incudes a summary of the differential expression analysis with top 30 genes up- and down-regulated by soy protein isolate (SPI), estradiol (E2) and SPI+E2. Additional functional annotation analysis of KEGG pathways is also presented for each treatment, together with networks of interaction between those pathways. Further interpretation and discussion of this data can be found in the article "Uterine responses to feeding soy protein isolate and treatment with 17ß-estradiol differ in ovariectomized female rats" Ronis et al. (2016) [1].

Uterine responses to feeding soy protein isolate and treatment with 17ß-estradiol differ in ovariectomized female rats.

There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 µg/kg/d 17ß-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P<0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P<0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P<0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens.

A Pre-fabricated Bracing System for the Management of Humeral Shaft Fractures: Experience of a Centre in the United Kingdom.

BACKGROUND: The aim of our study is to evaluate the ability of a pre- fabricated humeral bracing system in providing sufficient stability to fracture union and carry out a cost analysis comparing bracing versus surgical fixation for these fractures. MATERIAL AND METHODS: A review of humeral shaft fractures treated with a pre-fabricated humeral bracing system was undertaken. RESULTS: 20 humeral fractures (20 patients) were included. Mean patient age was 56.8 years (range 16- 89). There were 14 AO type A, 3 type B and 3 type C fractures. Median time interval from fracture to brace application was 8 days (range 0-41). Clinical and radiological union was achieved in 15 humeri (75%). Median time to clinical and radiological union was 80 days (range 32-434). The cost of treating humeral shaft fractures surgically by plating and by humeral bracing was estimated at £ 2292.99 and £ 1228 per case, respectively. CONCLUSIONS: 1. A pre-fabricated bracing system is an efficacious and cost-effective modality for humeral shaft fracture treatment. 2. It may, however, lead to a high non-union rate as well as shoulder and elbow stiffness. 3. A prospective randomized trial comparing bracing with internal fixation of humeral shaft fractures is needed.

Benign elevations in serum aminotransferases and biomarkers of hepatotoxicity in healthy volunteers treated with cholestyramine.

BACKGROUND: There are currently no serum biomarkers capable of distinguishing elevations in serum alanine aminotransferase (ALT) that portend serious liver injury potential from benign elevations such as those occurring during cholestyramine treatment. The aim of the research was to test the hypothesis that newly proposed biomarkers of hepatotoxicity would not significantly rise in serum during elevations in serum ALT associated with cholestyramine treatment, which has never been associated with clinically relevant liver injury. METHODS: In a double-blind placebo-controlled trial, cholestyramine (8g) was administered for 11 days to healthy adult volunteers. Serum from subjects with elevations in alanine aminotransferase (ALT) exceeding three-fold the upper limit of normal (ULN) were utilized for biomarker quantification. RESULTS: In 11 of 67 subjects, cholestyramine treatment resulted in ALT elevation by >3x ULN (mean 6.9 fold; range 3-28 fold). In these 11 subjects, there was a 22.4-fold mean increase in serum levels of miR-122 relative to baseline, supporting a liver origin of the serum ALT. Significant elevations were noted in mean levels of necrosis biomarkers sorbitol dehydrogenase (8.1 fold), cytokeratin 18 (2.1 fold) and HMGB1 (1.7 fold). Caspase-cleaved cytokeratin 18, a biomarker of apoptosis was also significantly elevated (1.7 fold). A rise in glutamate dehydrogenase (7.3 fold) may support mitochondrial dysfunction. CONCLUSION: All toxicity biomarkers measured in this study were elevated along with ALT, confirming the liver origin and reflecting both hepatocyte necrosis and apoptosis. Since cholestyramine treatment has no clinical liver safety concerns, we conclude that interpretation of the biomarkers studied may not be straightforward in the context of assessing liver safety of new drugs.

The use of routine preoperative magnetic resonance imaging in identifying intraspinal anomalies in patients with idiopathic scoliosis: a 10-year review.

PURPOSE: This study sought to quantify the frequency of previously unidentified spinal cord anomalies identified by routine preoperative magnetic resonance imaging (MRI), in patients planned for surgical scoliosis correction. METHODS: Our study group comprised 206 patients with idiopathic scoliosis who underwent deformity correction from 1998 to 2008. Clinical records of all the patients were retrospectively reviewed to ascertain the proportion having a neural abnormality on preoperative MRI scan. RESULTS: Twenty of 206 patients (9.7 %) were diagnosed with an unexpected intraspinal anomaly on routine preoperative MRI. In all cases, a neurosurgical opinion was sought prior to further intervention. Of the 20 patients, 11 underwent a neurosurgical procedure (de-tethering of cord, decompression of Chiari, decompression of syrinx). There was no statistically significant difference between the group of patients who had intrinsic spinal cord anomalies on preoperative MRI and those did not have a cord abnormality with regard to age at presentation, gender, side of dominant curve and degree of curve (p < 0.05). CONCLUSION: The high frequency of spinal cord abnormalities unidentified by preoperative neurological examination, and the frequent need for subsequent neurosurgical intervention, suggests that MRI assessment prior to deformity correction is important in the management of idiopathic scoliosis.

Perioperative care of a patient with refractory idiopathic thrombocytopenic purpura undergoing total knee arthroplasty.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement.

Mammary gland morphology and gene expression differ in female rats treated with 17ß-estradiol or fed soy protein isolate.

Soy foods have been suggested to have both positive health benefits and potentially adverse effects as a result of their content of phytoestrogens. However, studies on the estrogenicity of soy foods are lacking. Here we directly compared the effects of soy protein isolate (SPI), the protein in soy infant formula, with those of 17ß-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were fed AIN-93G diets containing casein or SPI beginning on postnatal d 30. Rats were ovariectomized on postnatal d 50 and treated with 5 µg/kg/d E2 or vehicle for 14 d. Microarray analysis revealed that E2 treatment altered expression of 780 genes more than or equal to 2-fold (P < 0.05), whereas SPI feeding altered expression of only 53 genes more than or equal to 2-fold. Moreover, the groups had only 10 genes in common to increase more than or equal to 2-fold. The combination of SPI feeding and E2 altered expression of 422 genes and reversed E2 effects on many mRNAs, including those involved in the c-myc signaling pathway, cyclin D1, and Ki67. ERα binding to its response element on the Tie-2/Tek and progesterone receptor promoters was increased by E2, but not SPI, and this promoter binding was suppressed by the combination of E2 + SPI for the Tie-2/Tek promoter but increased for the progesterone receptor promoter (P < 0.05). SPI reduced the ratio of epithelial to fat pad area and E2 + SPI reduced both epithelial and fat pad area (P < 0.05). These data suggest that SPI is only minimally estrogenic in the rat mammary gland even in the absence of endogenous estrogens.

Anterior cruciate ligament graft choices: a review of current concepts.

The graft choice for anterior cruciate ligament (ACL) reconstruction continues to be controversial. There are several options available for the treating surgeon, including Bone Patellar Tendon Bone (BPTB) grafts, Hamstring tendon (HT) grafts, allografts and synthetic grafts. Within the last decade there have been several comparative trials and meta-analysis, which have failed to provide an answer with regards to the best graft available. The aim of this review is to understand the current concepts in graft choices for ACL reconstruction.

Distal radius volar locking plates: does a variable angle locking system confer a clinical advantage?

This retrospective study compared clinical, radiological and subjective outcomes between patients with a distal radius fracture fixed with a variable angle or fixed angle volar locking plate. Radiological parameters were assessed between initial and final post-operative films. Post-operative clinical range of motion as a proportion of that in the opposite wrist was assessed clinically, and satisfaction and subjective outcomes were assessed by questionnaire. One hundred and seven patients were included in the study; 65 underwent fixation with a variable angle and 42 with a fixed angle locking plate. There were five complications and secondary operations in each group. There was no significant difference between the groups in radiological parameters measured or the proportional range of motion. Visual analogue scale, Mayo Wrist and Quick DASH scores were not significantly different between the groups. Neither the subjective nor clinical outcomes of this study demonstrated clinical superiority of either plate system.

Teaching basic shoulder ultrasonography to orthopaedic postgraduate trainees--effectiveness of a training workshop.

AIM: Ultrasound examination of the shoulder conducted by orthopaedic surgeons in the diagnosis and treatment of shoulder conditions is increasingly reported. Shoulder ultrasound is not a mandatory component of postgraduate orthopaedic training in the United Kingdom. The aim of this study was to assess the effectiveness of the shoulder ultrasound teaching workshop administered to postgraduate orthopaedic surgical trainees. METHODS: Orthopaedic trainees participated in a teaching workshop on shoulder ultrasound examination with particular emphasis on demonstrating the Acromioclavicluar joint (ACJ) and the long head of the biceps (LHB) in the biciptal groove. The ability of the trainees to demonstrate the ACJ and the LHB using ultrasound was then assessed. RESULTS: Thirty three orthopaedic trainees participated in this study. Twenty three (70%) trainees were able to demonstrate the ACJ and 14 (42%) trainees were able to demonstrate the LHB without assistance, following the ultrasound teaching workshop. The skills acquired by the trainees were independent to the year in training and previous shoulder experience (p > 0.05). CONCLUSION: Our study shows that a basic shoulder ultrasound teaching workshop can be effective in equipping postgraduate orthopaedic trainees with basic ultrasound techniques. It could potentially become part of a structured orthopaedic training programme.

Complement activation in acetaminophen-induced liver injury in mice.

Overdose with acetaminophen (APAP) results in acute liver failure in humans and experimental animals. Complement comprises more than 30 proteins that can participate in tissue injury and/or repair, but the role of complement activation in APAP-induced hepatotoxicity has not been evaluated. Treatment of male, C57BL6J mice with APAP (200-400 mg/kg) resulted in liver injury as evidenced by increased activity of alanine aminotransferase (ALT) in plasma and hepatocellular necrosis. Plasma concentration of the complement component C3 was significantly reduced 6 h after treatment with APAP, indicating complement activation, and C3b (detected by immunostaining) accumulated in the centrilobular areas of liver lobules. Pretreatment with cobra venom factor (CVF; 15 U/mouse) to deplete complement components abolished APAP-mediated C3b accumulation, and this was accompanied by reductions in plasma ALT activity, hepatocellular necrosis, hepatic neutrophil accumulation, and expression of inflammatory genes (interleukin-6, interleukin-10, and plasminogen activation inhibitor-1) at 24 h after APAP treatment. Loss of hepatocellular GSH was similar in APAP-treated mice pretreated with either saline or CVF, suggesting that CVF pretreatment did not affect APAP bioactivation. Mice with a genetic deficiency in C3 had reduced ALT activity 6 and 12 h after APAP administration compared with wild-type animals. These results reveal a key role for complement activation in hepatic inflammation and progression of injury during the pathogenesis of APAP-induced hepatotoxicity.

Delayed diagnosis of traumatic hip dislocation mimicking Perthes disease in a child.

Traumatic hip dislocations in children are uncommon, yet even trivial injuries may result in dislocation. Avascular necrosis (AVN) occurs in 3-6% of dislocations if reduction is performed within the first 4 h, however, the incidence rises to 66% if the reduction is performed 24 h after dislocation. Awareness and early identification is therefore critical to long term prognosis. The authors report a case of a relatively trivial trauma resulting in hip dislocation in a 5-year-old boy. This case is useful in highlighting that (a) hip dislocation may occur in children with relatively trivial mechanisms, (b) knee pain often indicates an underlying hip pathology and (c) traumatic AVN follows a similar course to Perthes disease and therefore may be management should be tailored in a similar manner to achieve containment within the acetabulum.

Carbohydrate-responsive gene expression in the adipose tissue of rats.

Although obesity is often associated with high-fat diets, it can develop from a variety of meal patterns. Excessive intake of simple carbohydrates is one consistent eating behavior leading to obesity. However, the impact of overconsumption of diets with high carbohydrate to fat ratios (C/F) on body composition and global adipose tissue gene expression remains unclear. We used total enteral nutrition to evaluate the effects of caloric intake and C/F on body weight gain and development of obesity. Female Sprague Dawley rats were fed diets with either low C/F or high C/F (HC) (reflecting a 19.5-fold increase in C/F) at two levels of caloric intake: 187 or 220 kcal/kg(3/4) x d (15% excess) for 4 wk. At the end of the study period, rats fed HC diets had about 20% higher body weight at either caloric intake compared with rats fed low C/F diets (P < 0.05). Body composition (assessed by nuclear magnetic resonance, computerized tomography, and adipose tissue weights) revealed higher percent fat mass (P < 0.05) in HC rats. Obesity was associated with increased serum resistin, leptin, fasting hyperinsulinemia, and insulin resistance after an oral glucose challenge (P < 0.05). Microarray analyses of adipose tissues revealed HC diets led to changes in 270 and 464 transcripts at 187 and 220 kcal/kg(3/4) x d intakes. Genes regulating glucose transport, glycolysis, fatty acid and triglyceride biosynthesis, desaturation and elongation, adipogenesis, and adipokines were affected by HC diets. These results suggest that C/F and interactions with excessive caloric intake per se may regulate body composition and play important roles in the development of obesity and metabolic syndrome.

Hepatic gene expression following consumption of soy protein isolate in female Sprague-Dawley rats differs from that produced by 17{beta}-estradiol treatment.

Although soy foods have been recognized as an excellent source of protein, there have been recent concerns regarding potential adverse effects of isoflavone phytochemicals found in soy products, which are known to bind and activate estrogen receptors. Here, we used global hepatic gene expression profiles in ovariectomized female Sprague-Dawley rats treated with 17beta-estradiol (E(2)) or fed with soy protein isolate (SPI) as a means of estimating potential estrogenicity of SPI. Female Sprague-Dawley rats were fed AIN-93G diets containing casein (CAS) or SPI starting at postnatal day (PND) 30. Rats were ovariectomized on PND 50 and infused with E(2) or vehicle in osmotic pumps for 14 d. Microarray analysis was performed on liver using Affymetrix GeneChip Rat 230 2.0. Serum E(2) levels were within normal ranges for the rat and SPI feeding did not increase uterine wet weight in the absence or presence of E(2). SPI feeding altered (P<0.05, >or=+/-1.5-fold) the expression of 82 genes, while E(2) treatment altered 892 genes. Moreover, only 4% of E(2)-affected genes were also modulated by SPI, including some whose expression was reversed by SPI feeding. The interaction between E(2) and SPI uniquely modulated the expression profile of 225 genes including the reduction of those involved in fatty acid biosynthesis or glucocorticoid signaling and an induction of those involved in cholesterol metabolism. The different hepatic gene signatures produced by SPI feeding compared with E(2) and the lack of increase in uterine wet weight in rats fed with SPI suggest that SPI is not estrogenic in these tissues.