Subscapularis Repair in Reverse Total Shoulder Arthroplasty: Differences in Outcomes Based on Preoperative Quality of Subscapularis Tendon.

Purpose: This study examines the influence of preoperative fatty infiltration (FI) of the subscapularis tendon (SBS) on outcomes following reverse total shoulder arthroplasty (rTSA) with SBS repair. Methods: A cohort of 161 rTSA patients with SBS repair, followed for a mean of 45.3 months, was divided into three groups based on FI: Group A (intact upper and lower portions, n = 85), Group B (intact lower portions, n = 44), and Group C (fatty infiltrated in both portions, n = 32). The mean age was 74.5 years (range: 65-95). Results: Preoperative FI displayed significant disparity among the groups: Group A (1.18 ± 0.60), Group B (2.95 ± 0.56), and Group C (4.0 ± 0.00) (p < .001). Group A exhibited a more positive trend in activities of daily living, particularly in toileting ability (81% in Group A, 68% in Group B, and 72% in Group C), although without statistical significance (p = 0.220). Complication rates varied: Group A had seven acromial fractures (8%), three cases of instability (3%), and six instances of scapular notching (7%). Group B experienced four acromial fractures (9%) and four cases of scapular notching (9%), while Group C had only one case of scapular notching (3%) (p = 0.733). Conclusion: In cases characterized by favorable preoperative SBS quality, there was an elevation in functional internal rotation (IR) post-surgery, accompanied by an increased incidence of postoperative complications. Hence, careful consideration is advised when determining the necessity for SBS repair. Level of Evidence: Level III, retrospective comparative study.

Does timing influence rehabilitation outcomes in arthroscopic rotator cuff repair with biceps rerouting? a prospective randomized study.

BACKGROUND: Arthroscopic rotator cuff repair with biceps rerouting (ABR) has emerged as a reliable option for treating large posterosuperior rotator cuff tears (RCTs). This study aims to compare functional and structural outcomes of early vs. delayed motion rehabilitation protocols following ABR. METHODS: A total of 101 patients with semirigid, large, posterosuperior RCTs undergoing ABR were randomized into 2 groups: group I (early motion) with 53 patients (34 females, 19 males) and group II (delayed motion) with 48 patients (31 females, 17 males). In group I, the mean age was 63.9 years (range, 46-79), and in group II, it was 65.4 years (range, 43-78). The mean follow-up periods for group I and group II were 16.2 and 15.5 months, respectively. Preoperative and postoperative assessments were conducted at 3, 6, and 12 months, with structural integrity assessed with magnetic resonance imaging at a minimum follow-up of 12 months. Statistical analyses were performed to compare outcomes between the 2 groups. RESULTS: Both groups demonstrated significant improvements in visual analog scale score (group I: 4.0-1.6, group II: 3.7-1.4, P = .501), University of California-Los Angeles shoulder score (group I: 21.5-31.4, group II: 22.4-30.6, P = .331), and acromiohumeral interval (group I: 8.2 mm-9.1 mm, group II: 8.6 mm-9.5 mm, P = .412), with no statistically or clinically meaningful differences. Active range of movements (ROM) were not significantly different between groups, except for active forward flexion at 3 months (group I: 140.1°, group II: 119.2°, P = .006), that was not shown to be translated clinically into differences in function or healing between the groups in this study. Notably, retear rates were similar between groups (group I: 22.6%, group II: 20.8%, P = .826). CONCLUSION: This study's findings reveal no clinically discernible differences in active range of motion at 1-year follow-up between patients who underwent ABR for semirigid, large, posterosuperior RCTs and were assigned to either early or delayed motion protocols. Notably, the early motion group demonstrated a plateau in maximum range of movement improvement as early as 3 months postsurgery. Based on these results, implementing an early motion protocol is recommended as an effective approach in the postoperative rehabilitation following ABR.

Rotator cuff repairs with all-suture tape anchors: no difference in outcomes between with or without all-suture tape anchors.

PURPOSE: This study aimed at comparing the outcomes of medium- to large-sized rotator cuff repairs performed using the suture bridge technique either with or without tape-like sutures, and single row techniques with conventional sutures. METHODS: A total of 135 eligible patients with medium to large rotator cuff tears were identified and analyzed retrospectively, from 2017 to 2019. Only repairs using all-suture anchors were included in the study. Patients were divided into the following three groups: single-row (SR) repair (N = 50), standard double-row suture bridge (DRSB) repair with conventional sutures (N = 35), and DRSB with tape-like sutures (N = 50). The average postoperative follow-up period was 26.3 ± 9.8 months (range, 18-37). RESULTS: DRSB with tapes had the highest re-tear rate of 16% (8/50), but there was no significant difference with the re-tear rates observed in SR (8%, 4/50) and DRSB with conventional sutures (11.4%, 4/35) (n.s.). DRSB with tapes demonstrated higher rate of type 2 re-tears (10%) compared to type 1 re-tears (6%), but the other two groups showed either similar or higher rates of type 1 re-tears compared to that of type 2. Post-operative functional scores of the three groups improved significantly (all p < 0.05), but the differences between the groups were not statistically significant. CONCLUSIONS: No clinical difference in functional outcomes and re-tear rates were observed in DRSB with tapes when compared with SR and DRSB using the conventional sutures. Tape-like DRSB suture which was expected to be superior by its biomechanical advantage was clinically non-superior to conventional DRSB suture. There were no significant differences in VAS scores and UCLA scores. LEVEL OF EVIDENCE: Level III.

Association of Insufficient or Excess Sleep with Type 2 Diabetes Mellitus in the Presence of Periodontitis.

We aimed to investigate the effects of sleep duration on impaired fasting glucose and diabetes in Korean adults with periodontal disease. This cross-sectional study was performed using data for 10,465 subjects aged >19 years who completed the periodontal examination and questionnaires in the Sixth Korea National Health and Nutrition Examination Survey (2013-2015). The effect of sleep was confirmed by a complex-sample multinomial logistic regression analysis. Confounding variables were age, sex, household income, education level, smoking status, and sleep duration. Of all participants, 25.7% had periodontitis, of which 28.6% had fasting serum glucose disorder and 14.2% had diabetes. Among participants with periodontitis, the prevalence of diabetes was 1.49 times higher in participants with an average sleep duration of ≥8 h than those with an average sleep duration of 6-7 h. The prevalence of diabetes among participants without periodontitis was 1.49 times and 1.57 times higher in participants with an average sleep duration of ≤5 and ≥8 h, respectively, than those with an average sleep duration of 6-7 h. We found that altered sleep duration may be a risk factor for diabetes and that proper sleep duration is important to control diabetes incidence.

Factors Related to the Number of Existing Teeth among Korean Adults Aged 55-79 Years.

This study aimed to determine the association between the number of existing teeth (NET) and socioeconomic status (SES), oral health-related behaviours, and metabolic syndrome in Korean adults aged 55-79 years. The study included 3255 adults who underwent oral health examinations and answered questionnaires regarding SES, oral health-related behaviours, and metabolic diseases in the Sixth Korea National Health and Nutrition Examination Survey (2013-2015). The dependent variable was the binary status based on the median NET in each age group. The independent variables were based on SES, oral health-related behaviours, and the presence of metabolic syndrome. The study findings showed that the factors associated with the NET were sex, household income, education level, region of residence, daily toothbrushing frequency, dental visit within 1 year, smoking, and metabolic syndrome. NET was lower in males (adjusted OR: 0.74), in low household income group (adjusted OR: 0.77), in primary school graduates (adjusted OR: 0.53), in rural residents (adjusted OR: 0.78), and in medicaid beneficiaries (adjusted OR: 0.78). The interventions aimed at preserving existing teeth in elderly population should consider their SES, oral health-related behaviours, and metabolic syndrome and overhauling current oral healthcare system and redefining the roles of oral health professionals.

Production of Membrane Vesicles by Enterococcus faecium Cultured With or Without Subinhibitory Concentrations of Antibiotics and Their Pathological Effects on Epithelial Cells.

Enterococcus faecium is a clinically important pathogen associated with opportunistic infection and multi-drug resistance. E. faecium has been shown to produce membrane vesicles (MVs), but MV production by E. faecium under antibiotic stress conditions and the pathogenic traits thereof have yet to be determined. This study investigated the production of MVs in E. faecium ATCC 700221 cultured with sub-minimum inhibitory concentrations (MICs) of vancomycin or linezolid and determined their pathologic effects on colon epithelial Caco-2 cells. E. faecium ATCC 700221 cultured with 1/2 MIC of vancomycin or linezolid produced 3.0 and 1.5 times more MV proteins than bacteria cultured without antibiotics, respectively. Totals of 438, 461, and 513 proteins were identified in MVs from E. faecium cultured in brain heart infusion broth (MVs/BHI), BHI broth with 1/2 MIC of vancomycin (MVs/VAN), or BHI broth with 1/2 MIC of linezolid (MVs/LIN), respectively. Intact MVs/BHI induced cytotoxicity and the expression of pro-inflammatory cytokine and chemokine genes in Caco-2 cells in a dose-dependent manner, but proteinase K-treated MVs significantly suppressed these pro-inflammatory responses. MVs/LIN were more cytotoxic toward Caco-2 cells than MVs/BHI and MVs/VAN, whereas MVs/VAN stimulated more pro-inflammatory cytokine gene expression in Caco-2 cells than MVs/BHI and MVs/LIN. Overall results indicated that antibiotics modulate the biogenesis and proteomes of MVs in E. faecium at subinhibitory concentrations. MVs produced by E. faecium cultured under antibiotic stress conditions induce strong host cell responses that may contribute to the pathogenesis E. faecium.

Association between Periodontitis and Metabolic Syndrome in a Korean Nationally Representative Sample of Adults Aged 35-79 Years.

This study aimed to evaluate the association between periodontitis and metabolic syndrome (MetS) and to investigate risk factors associated with MetS in Korean adults aged 35 to 79 years. Among individuals aged 35-79 years who participated in the Korea National Health and Nutrition Examination Survey 2013-2015, 8314 participants who completed the required examinations and questionnaires were included. Confounding variables related to demographic and socioeconomic status and systemic and oral health-related behaviors were age, gender, household income, education level, smoking, alcohol intake, physical activity, and frequency of daily toothbrushing. Of the 8314 participants, 32.2% were diagnosed with MetS. The prevalence of MetS was 26.6% and 41.6% in those without and with periodontitis, respectively. Among individuals with periodontitis, the prevalence of MetS was 44.3% in males and 36.9% in females. Compared to non-periodontitis, periodontitis was associated with MetS (adjusted OR = 1.422, 95% CI: 1.26-1.61). Age, frequency of daily toothbrushing, and periodontitis were associated with MetS in both males and females. While current smoking and alcohol intake more than twice a week were significantly associated with MetS in males, household income and education level were significantly associated with MetS in females. The findings suggest that periodontitis can be associated with MetS.

Association of stress, depression, and suicidal ideation with subjective oral health status and oral functions in Korean adults aged 35 years or more.

BACKGROUND: Oral health greatly affects well-being throughout the different stages of life from childhood to late adulthood. Loss of teeth due to poor oral health hinders mastication, leading to poor nutrition absorption, and affects pronunciation and aesthetics, leading to interpersonal difficulties. As social activities become limited, a sense of isolation and loneliness, stress, and depression grows while happiness decreases. This study aimed to examine the association of stress, depression, and suicidal ideation with oral health status and oral functions in a large nationwide sample of Korean adults aged 35 years or more. METHODS: The sample comprised 15,716 adults, selected using a rolling survey sampling method and data were extracted from the Fifth Korea National Health and Nutrition Examination Survey (KNHANES) (2010-2012). Participants were interviewed about their self-evaluation of health including oral health status and mental health, such as stress, depression, and suicidal ideation. Data from 11,347 adults were finally selected after excluding participants with missing answers. The dependent variables were stress, depression, and suicidal ideation. The independent variables were gender, age, household income, education, smoking, drinking, oral health perception, chewing, and speaking. Complex samples logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Participants met the criteria for stress (25.4%), depression (13.0%), and suicidal ideation (13.9%). Subjective oral health status was not significantly associated with stress, depression, and suicidal ideation. However, the presence of very uncomfortable chewing problems was significantly associated with stress (OR = 2.294, 95% CI = 1.41, 3.72), depression (OR = 3.232, 95% CI = 1.97, 5.31), and suicidal ideation (OR = 2.727, 95% CI = 1.58, 4.72). The presence of very uncomfortable speaking problems was significantly associated with stress (OR = 1.592, 95% CI = 1.13, 2.24) but not significantly associated with depression and suicidal ideation. CONCLUSIONS: Oral functional problems including chewing and speaking difficulties can be associated with mental health. It is necessary to develop oral health promotion programs for adults and help them maintain a good quality of life and mental health.

Phase I and pharmacodynamic study of vorinostat combined with capecitabine and cisplatin as first-line chemotherapy in advanced gastric cancer.

A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat was dosed at 300-400 mg once daily on Days 1-14, capecitabine at 800-1,000 mg/m(2) twice daily on Days 1-14, and cisplatin at 60-80 mg/m(2) on Day 1. To assess the pharmacodynamics of vorinostat, histone H3 acetylation was assessed in peripheral blood mononuclear cells before the study treatment and at Day 8 of cycle 1. In total, 30 patients with unresectable or metastatic gastric adenocarcinoma were included. Dose-limiting toxicities were thrombocytopenia, fatigue, stomatitis, and anorexia. The following doses were recommended for phase II trial: 400 mg of vorinostat once daily, 1,000 mg/m(2) of capecitabine twice daily, and 60 mg/m(2) of cisplatin. The most common grade 3-4 toxicities were neutropenia (47 %), anorexia (20 %), thrombocytopenia (17 %), and fatigue (13 %). In overall, response rate was 56 % (95 % confidence interval [CI]: 32-81). With a median follow-up of 14.1 months, the median progression-free survival and overall survival were 7.1 months (95 % CI: 3.8-10.3) and 18.0 months (95 % CI: 4.8-31.1), respectively. The change in H3 acetylation after treatment with vorinostat correlated significantly with the vorinostat dose (300 vs. 400 mg/day) and the baseline level of H3 acetylation before treatment. Three-weekly vorinostat-XP regimen is feasible and recommended for further development in advanced gastric cancer.

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis.

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis.

Peroxisome proliferator-activated receptor-gamma expression in the lung tissue of obese rats.

PURPOSE: Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator- activated receptor (PPAR)-γ has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-α, PPAR-γ, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-α are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats. MATERIALS AND METHODS: Obese and lean rats were given with a high fat diet or a 30% restricted diet for 32 weeks, and their blood glucose levels and weights were monitored. After 32 weeks, mRNA levels of PPAR-α, PPAR-γ, AdipoR1, AdipoR2, leptin, and TNF-α in lung tissues were measured using real time PCR. RESULTS: PPAR-α, PPAR-γ, AdipoR1, AdipoR2, leptin, and TNF-α were expressed in both obese and lean rat lung tissues. Increased serum glucose levels on intraperitoneal glucose tolerance testing and a higher weight gain at 32 weeks were observed in OLETF control rats compared to OLETF diet restricted rats. PPAR-γ expression was markedly elevated in obese control and diet restricted rats compared to lean rats, although PPAR-γ expression in obese rats was not affected by diet restriction. Leptin was highly expressed in OLETF rats compared to LETO rats. TNF-α expression was enhanced in OLETF control rats compared LETO diet restricted rats, and decreased by diet restriction. PPAR-α, AdipoR1, and AdipoR2 expression were not significantly different between obese and lean rats. CONCLUSION: PPAR-γ was highly expressed in the lung tissues of obese rats and may be a novel treatment target for regulating lung inflammation associated with obesity.

Effects of postnatal age and aminophylline on the maturation of amplitude-integrated electroencephalography activity in preterm infants.

BACKGROUND: The use of amplitude-integrated electroencephalography (aEEG) is increasing during the neonatal intensive care of preterm infants. OBJECTIVE: This prospective study was designed to assess factors that affect the maturation of aEEG activity in preterm infants with a gestational age (GA) of <32 weeks. METHODS: aEEGs with cerebral function monitoring were performed weekly in preterm infants, and the recordings were evaluated and scored to assess the degree of continuity, the degree of sleep-wake cycling, and the amplitude of the lower border. Subjects with any of the following conditions were excluded: intraventricular hemorrhage or periventricular leukomalacia on cranial ultrasonography, sedation, hypotension, or respiratory instability (FiO(2) >50%). RESULTS: The authors analyzed 207 recordings in 35 infants (GA 24-31 weeks, birth weight 440-1,980 g, postmenstrual age 25-38 weeks). At postmenstrual age 34-36 weeks, the aEEG total score was higher in preterm infants with a GA from 24 to 28 weeks than in less premature infants with a GA from 29 to 31 weeks (aEEG total score 12 vs. 10, p < 0.05). Logistic regression analysis revealed that the sleep-wake cycling was more prominent in infants with higher postnatal age (OR 3.32, 95% CI 2.40-4.59) or those receiving aminophylline (OR 3.28, 95% CI 1.06-10.08). CONCLUSIONS: The maturation of aEEG activity was found to be significantly correlated with postnatal age and with aminophylline use in clinically stable preterm infants. Most notably, aminophylline was found to be significantly associated with the degree of sleep-wake cycling as indicated by aEEG activity.

The relationship between coronary artery calcification score, plasma osteoprotegerin level and arterial stiffness in asymptomatic type 2 DM.

Because T2DM increases the risk of coronary atherosclerosis and CAD and new noninvasive techniques to assess CVD risk have gained considerable popularity, it is important to know how these tools relate to each other. The aim of this study was to evaluate the relationship between the extent of coronary artery calcification measured by MDCT, plasma OPG levels, baPWV and the established cardiovascular risk factors in Korean patients with T2DM. From November 2006 to December 2007, 110 asymptomatic Korean patients with T2DM without prior evidence of CAD were assessed (mean age 57.2 years). CAC imaging was performed using a 40-slice MDCT. Serum OPG levels were measured by an enzyme-linked immunosorbent assay (Oscotec, Korea) from the serum samples of each subject. We measured the baPWV as an index of arterial stiffness. In addition, we measured fasting glucose, HbA(1)C, hsCRP and lipid profiles. A total of 74 patients (67.3%) had minimal or insignificant CAC (<10). The CACS, OPG and baPWV showed significant positive correlations with each other. The CACS was significantly associated with the baPWV, smoking and use of a statin. The baPWV was significantly associated with age, duration of DM, total cholesterol and CACS by multiple linear regression models of the dependent variables of CACS or baPWV. CAC and baPWV were significant predictors of each other (r = 0.359, P = 0.014 and r = 0.361, P = 0.004). The results of this study showed that CAC, baPWV and serum OPG levels were significantly correlated with each other in asymptomatic Korean patients with T2DM. Furthermore, our results suggest that arterial stiffness, as determined by baPWV, may predict the extent of coronary calcification by MDCT.

The risk of metabolic syndrome according to the high-sensitivity C-reactive protein in apparently healthy Koreans.

BACKGROUND: Recently, considerable interest has been focused on the positive relationship between inflammation and the metabolic syndrome (MS). Therefore, we investigated whether the baseline plasma levels of the high-sensitivity C-reactive protein could be associated with future risk for MS in apparently healthy Koreans. METHODS: A total of 1132 subjects (767 men, 365 women with a mean age of 49 years), who underwent health examination at this hospital in both 2002 and 2005 were enrolled. The criteria for metabolic syndrome followed that of NCEP-ATP III guideline except waist circumference. Instead, BMI (>/=25 kg/m(2)) was used for the measurement for obesity. RESULTS AND CONCLUSIONS: The relative risks of future MS in the highest quartile of high-sensitivity C-reactive protein at baseline were 2.4 (95% confidence interval [CI], 1.3-4.2) as compared to the subjects in the lowest quartile. Positive associations persisted after adjustment for age, sex and smoking; multivariate relative risks for the highest vs lowest quartiles were 2.3 (95% CI, 1.3-4.1; P for trend=0.005). This retrospective study suggests that elevated levels of high-sensitivity C-reactive protein could be associated with incident MS.

Identification of adiponectin and its receptors in human osteoblast-like cells and association of T45G polymorphism in exon 2 of adiponectin gene with lumbar spine bone mineral density in Korean women.

OBJECTIVE: The role of adiponectin in bone metabolism has been recently reported in in vitro and in vivo studies. There has been no report on the association of adiponectin gene polymorphism and bone mineral density (BMD). Therefore, we investigated whether two single nucleotide polymorphisms (SNPs), T45G and G276T, in the adiponectin gene were related to BMD in Koreans. We also report on the identification of adiponectin and its receptors 1 and 2 in human osteoblast-like cell lines. PATIENTS AND MEASUREMENTS: MG-63 cells were cultured and osteogenic and adipogenic differentiations from human mesenchymal stem cells (hMSCs) were performed. RNA was then extracted from the cultured cells and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using primers for adiponectin and for the adiponectin receptor genes. In 249 female and 80 male subjects, measurements were made of their lumbar spine and femoral neck BMDs, and biochemical markers of bone turnover. The genotyping of the T45G polymorphism in exon 2 and the G276T polymorphisms in intron 2 in the adiponectin gene was performed using an allelic discrimination assay with a TaqMan probe. Analyses were performed separately in each cohort. RESULTS: We found that the mRNAs for adiponectin and for adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) were expressed in the MG-63 cells. Sequencing of the PCR products revealed that they were identical to human adiponectin, AdipoR1 and AdipoR2, respectively. mRNAs for adiponectin, AdipoR1 and AdipoR2 were also expressed in the osteoblastic and adipogenic cell lines differentiated from hMSCs. For the polymorphism study, the frequencies of T45G and G276T in the adiponectin gene were in compliance with Hardy-Weinberg equilibrium and the two polymorphisms were in complete linkage disequilibrium (D' = -1.0, P < 0.001). In the female cohort, subjects with G alleles at the T45G locus had significantly lower lumbar spine BMD than those subjects with the TT genotype. Although BMD levels showed no association with the G276T locus, the GT genotype group showed significantly higher urine deoxypyridinoline levels than other genotype groups. In the male cohort, no association was observed between adiponectin genotypes and BMD levels. CONCLUSIONS: We observed the expression of adiponectin, AdipoR1 and AdipoR2 in the MG-63 cell line and the osteoblastic cell line differentiated from hMSCs. T45G polymorphism in exon 2 of the adiponectin gene is associated with lumbar spine BMD and G276T polymorphism in intron 2 of the adiponectin gene is associated with the urine deoxypyridinoline level in Korean women. Additional studies are needed to elucidate the precise contribution of adiponectin to bone mineral metabolism.

Serum ghrelin and leptin levels in adult growth hormone deficiency syndrome.

BACKGROUND: In spite of the increasing information that has recently been accumulated on the involvement of ghrelin and leptin in the control of energy balance, the relationship between ghrelin and leptin and the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis in the pathological condition characterized by GH deficiency has been poorly clarified. Therefore, we performed this study to examine the correlation of the plasma levels of ghrelin and leptin with the anthropometric and biochemical markers in GH-deficient (GHD) adults as compared to their healthy cohorts. METHODS: In 60 male adults (GHD; n = 12, healthy control; n = 48, average age: 54 years), we investigated the correlations between the serum leptin and ghrelin levels with the anthropometric and biochemical factors in the control group, as compared to the GHD patients. The diagnosis of GH deficiency was made when peak response for serum GH was <5 microg/L to a GH-provocative test (L-dopa test). All subjects underwent assessment of waist circumference, body mass index (BMI) and percentage body fat for their body composition. Plasma ghrelin, leptin, insulin, GH and IGF-1 were measured. RESULTS: Groups were matched for age, BMI, waist circumference and percent of body fat. Ghrelin and leptin levels were not significantly different between the two groups. There was no correlation between the peak GH level or the GHAUC and the ghrelin concentrations in the GHD subjects. Plasma leptin correlated positively with percentage of body fat, total cholesterol and LDL-cholesterol, but it had no correlation with the peak GH or area under the curve for growth hormone (GHAUC) in the GHD subjects. Plasma ghrelin concentrations were not correlated with the biochemical and anthropometric markers in the subjects with GHD, and ghrelin showed no significant differences in the GHD and control subjects. Leptin concentrations were positively correlated with body fat, but they were not correlated with the levels of either IGF-1 or GH in the GHD patients. CONCLUSIONS: It is possible that ghrelin concentrations appeared normal in the GHD subjects because of the opposing influences of increased adiposity, which reduce ghrelin secretion, and GHD, which may increase it. Further studies are needed to clarify these controversies about the relation of ghrelin and leptin with the GH and IGF-1 levels.

Monoclonal anti-thrombopoietin antibodies generated by genetic immunization.

Thrombopoietin (TPO) is a megakaryocyte growth and differentiation factor that is currently being investigated as a therapeutic for cancer patients undergoing myelosuppressive chemotherapy. We generated monoclonal antibodies (MAbs) specific for human thrombopoietin (hTPO) by genetic immunization using an hTPO expression plasmid and an adjuvant plasmid that encodes mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). All genetically immunized mice exhibited a high humoral immune response. Splenocytes from these mice were used to generate hybridomas. Two MAbs, designated 2B9A10 and 4C16B15 (of IgG1 and IgG3 isotypes, respectively), were subsequently selected and produced. They specifically recognized and precipitated recombinant hTPO produced by mammalian cells and were effective in sandwich enzyme-linked immunosorbent assays (ELISAs) for hTPO quantitation. Our results demonstrate that these MAbs should be useful for purification and quantitation of hTPO in clinical and laboratory settings.

The effects of C161-->T polymorphisms in exon 6 of peroxisome proliferator-activated receptor-gamma gene on bone mineral metabolism and serum osteoprotegerin levels in healthy middle-aged women.

OBJECTIVE: We evaluated the association of different genotypes in C161-->T substitution in exon 6 of peroxisome proliferator-activated receptor-gamma (PPARgamma) gene with bone turnover markers, bone mineral density (BMD), and serum osteoprotegerin (OPG) in female subjects to reveal the role of PPARgamma in bone. STUDY DESIGN: In 263 healthy Korean women (mean age 52 years), anthropometric measurements were taken along with measurements of lumbar spine and femoral neck BMD, bone turnover markers, such as alkaline phosphatase, serum calcium, phosphorus, 24-hour urine calcium, phosphorus excretion, and urine deoxypyridinoline. Serum follicular stimulating hormone levels were measured and serum OPG levels were measured with the enzyme-linked immunosorbent assay method. Polymerase chain reaction-restriction fragment length polymorphism was performed. RESULTS: Allele frequencies were 0.804 for the C allele and 0.196 for the T allele. There were no differences in mean age, body mass index, BMD, and bone turnover markers among different genotypes, and the subjects with T alleles had significantly lower serum OPG levels. There were no differences in the prevalence of metabolic bone diseases according to the genotypes. When analyzed according to the menopausal status, only postmenopausal subjects with T alleles showed significantly lower serum OPG levels. CONCLUSION: The frequencies of C161-->T substitution in exon 6 of the PPARgamma gene in Korean females were similar to other races and women with T alleles showed significantly lower serum OPG levels and it was especially noted for postmenopausal subjects, which supports the possible concurrent association of PPARgamma and OPG with estrogen status in female subjects.

Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein.

OPG (osteoprotegerin) is an inhibitor of osteoclastogenesis and recent work suggests it has a role in atherosclerosis. Therefore we measured serum OPG levels in patients with coronary artery disease, compared the serum OPG levels among the different groups according to the number of stenotic vessels and determined whether there was any correlation with aortic calcification, LV (left ventricular) mass index and serum CRP (C-reactive protein) levels. Subjects (n=100; mean age, 57 years) who underwent coronary angiograms were enrolled. Blood pressure, body mass index, fasting blood glucose, lipid profiles and CRP levels were measured and the LV mass indices were calculated using ECGs. Serum OPG levels were measured by ELISA. The presence of calcification in the aortic notch was checked by a chest X-ray. The subjects were divided into four groups according to the number of stenotic vessels. The mean serum OPG levels increased significantly as the number of stenotic vessels increased, and the mean serum OPG levels were higher in the group with three-vessel disease compared with the groups with no- or one-vessel disease. The mean serum CRP level was significantly higher in the group with three-vessel disease compared with the groups with no-, one- and two-vessel disease. Age and LV mass index showed significant positive correlations with serum OPG levels, although significance was lost after an adjustment for age. Serum CRP levels were positively correlated with serum OPG levels even after an adjustment for age. There were no differences in serum OPG levels according to the presence of fasting hyperglycaemia or aortic calcification. In conclusion, serum OPG level was related to the severity of stenotic coronary arteries and serum CRP levels. LV mass indices showed no significant correlation with OPG levels. The precise mechanism for the role of OPG in atherosclerosis needs to be investigated further.