Minimally Invasive Total Hip Arthroplasty in a Patient with Hereditary Multiple Exostoses: A Case Report.

Hip geometry abnormalities found in patients with hereditary multiple exostoses (HME) could promote premature hip joint degeneration which needs treatment. We report the case of a 45-year old male with right hip arthrosis who underwent two-incision minimally invasive (MIS-2) total hip arthroplasty (THA), with satisfactory outcome. This technique could be an alternative approach for performing THA in patients with hereditary multiple exostoses.

MRI Features of Aquaporin-4 Antibody-Positive Longitudinally Extensive Transverse Myelitis: Insights into the Diagnosis of Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND PURPOSE: Longitudinally extensive transverse myelitis is a well-documented spinal manifestation of neuromyelitis optica spectrum disorders, however, other forms of nontumorous myelopathy can also manifest as longitudinally extensive transverse myelitis. Our aim was to evaluate the MR imaging features of aquaporin-4 antibody-positive longitudinally extensive transverse myelitis, which is strongly associated with neuromyelitis optica spectrum disorders. MATERIALS AND METHODS: We evaluated cervicomedullary junction involvement, cord expansion ratios, bright spotty lesions, the number of involved segments, skipped lesions, enhancement patterns, and axial distribution patterns using spinal MR imaging of 41 patients with longitudinally extensive transverse myelitis who underwent aquaporin-4 antibody testing. Univariate logistic regression analysis was performed to identify factors associated with aquaporin-4 antibody seropositivity, which were then used to develop a scoring system for diagnosing aquaporin-4 antibody-positive longitudinally extensive transverse myelitis. Interrater reliability for cord expansion ratio measurement and bright spotty lesions was determined using intraclass correlation coefficients and κ values, respectively. RESULTS: Fifteen patients with longitudinally extensive transverse myelitis were aquaporin-4 antibody-positive. Sex (female), cervicomedullary junction involvement, a cord expansion ratio of >1.4, and bright spotty lesions were significantly associated with aquaporin-4 antibody seropositivity. The sensitivity and specificity of the scoring system were 73.3% and 96.2%, respectively. The interclass correlation value for the cord expansion ratio was 0.78, and the κ value for bright spotty lesions was 0.61. CONCLUSIONS: Our scoring system, based on cervicomedullary junction involvement, higher cord expansion ratio, bright spotty lesions, and female sex, can facilitate the timely diagnosis of neuromyelitis optica spectrum disorders.

Differential protein stability and clinical responses of EML4-ALK fusion variants to various ALK inhibitors in advanced ALK-rearranged non-small cell lung cancer.

Background: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro. However, there are only limited data on the specific EML4-ALK variants and clinical responses of patients to various ALK inhibitors. Patients and methods: By multiplex reverse-transcriptase PCR, which detects 12 variants of known EML4-ALK rearrangements, we retrospectively determined ALK fusion variants in 54 advanced ALK rearrangement-positive NSCLCs. We subdivided the patients into two groups (variants 1/2/others and variants 3a/b) by protein stability and evaluated correlations of the variant status with clinical responses to crizotinib, alectinib, or ceritinib. Moreover, we established the EML4-ALK variant-expressing system and analyzed patterns of sensitivity of the variants to ALK inhibitors. Results: Of the 54 tumors analyzed, EML4-ALK variants 3a/b (44.4%) was the most common type, followed by variants 1 (33.3%) and 2 (11.1%). The 2-year progression-free survival (PFS) rate was 76.0% [95% confidence interval (CI) 56.8-100] in group EML4-ALK variants 1/2/others versus 26.4% (95% CI 10.5-66.6) in group variants 3a/b (P = 0.034) among crizotinib-treated patients. Meanwhile, the 2-year PFS rate was 69.0% (95% CI 49.9-95.4) in group variants 1/2/others versus 32.7% (95% CI 15.6-68.4) in group variants 3a/b (P = 0.108) among all crizotinib-, alectinib-, and ceritinib-treated patients. Variant 3a- or 5a-harboring cells were resistant to ALK inhibitors with >10-fold higher half maximal inhibitory concentration in vitro. Conclusion: Our findings show that group EML4-ALK variants 3a/b may be a major source of ALK inhibitor resistance in the clinic. The variant-specific genotype of the EML4-ALK fusion allows for more precise stratification of patients with advanced NSCLC.

Outcome of alternative approach to displaced acetabular fractures.

INTRODUCTION: Anatomical reduction of displaced acetabular fracture is not without its' limitations and complications. This study is conducted to assess clinical and radiological outcomes as well as complications of treating displaced acetabular fractures with emphasis on anatomical reduction in weight-bearing area, mainly the posterior column, and imperfect reduction of the anterior column is acceptable. However, stability of both columns is mandatory. METHODS: It was a retrospective study carried out in a Level 1 arthroplasty and trauma centre. 23 patients (17 males, 6 females) with average age of 50.1 years (range, 36-68 years) with displaced acetabular fracture treated with combined incisions and plate-cable systems were included. There were 3 elementary and 18 associated fractures according to Letournel classification. Average follow-up was 23.5 months (range, 12-38.7 months). Mean operation time was 160min (range: 75-320min). Functional scores were evaluated using Harris Hip Score (HHS) whilst reduction was assessed by Matta criteria. Any displacement of reduction, osteoarthritis, heterotopic ossification, and other complications was recorded. RESULT: 65.2% (15/23) of the patients obtained excellent HHS and 21.7% (5/23) had good HHS. There were 12 anatomical, 6 imperfect, and 5 poor reductions. No displacement was recorded in final follow-up. Complications documented: three lateral femoral cutaneous nerve injuries, two conversions to total hip arthroplasty, three Brooker stage 1 heterotrophic ossification, one pulmonary embolism and one screw irritation. No incidence of wound breakdown, infection and radiological osteoarthritis was reported. CONCLUSIONS: Imperfect reduction of the anterior column provided clinical outcomes that are as good as total anatomical reduction. This approach minimizes soft tissue damage and reduces perioperative morbidities.

Association between antiphospholipid antibodies and arterial thrombosis in patients with rheumatoid arthritis.

OBJECTIVES: Antiphospholipid antibodies (aPL) are present in a proportion of patients with rheumatoid arthritis but their clinical significance remains unclear. We investigated the association between aPL and thrombotic events in rheumatoid arthritis patients. METHODS: In this cross-sectional study, aPL profiles were evaluated in 376 rheumatoid arthritis patients in accordance with the standard guidelines. Clinical and radiographic data were retrospectively collected. RESULTS: aPL were identified in 39 patients (10.4%). Lupus anticoagulant was the most common subtype (n = 25, 6.6%); anti-cardiolipin antibodies and anti-ß2 glycoprotein I antibodies were detected in six and 12 patients (1.6% and 3.2%), respectively. Compared to the aPL-negative group, aPL-positive patients included more male patients (41.0% vs. 15.4%, P < 0.001) and more smokers (41.0% vs. 16.0%, P = 0.001). There was no difference between the two groups in age, disease duration and body mass index, or the frequency of diabetes, hypertension or dyslipidaemia. Of note, arterial thromboses were more common in the aPL-positive than the aPL-negative group (12.8% vs. 2.1%, P = 0.004), whereas the frequency of venous thrombosis did not differ between the two groups (0.0% vs. 0.9%, P = 1.000). On multivariate regression analysis, aPL, age, hypertension, dyslipidaemia and baseline C-reactive protein level were independently associated with arterial thrombotic events (all P values < 0.05). CONCLUSION: aPL was found in a subset of rheumatoid arthritis patients, who were more often smokers, and aPL was independently associated with development of arterial thrombosis. This result suggests that aPL may contribute to an increased risk of arterial thrombosis in rheumatoid arthritis patients.

PPARγ neddylation essential for adipogenesis is a potential target for treating obesity.

The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator-activated receptor gamma (PPARγ) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARγ is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARγ, leading to PPARγ stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARγ signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARγ.

Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress.

Pathologic alterations in podocytes lead to failure of an essential component of the glomerular filtration barrier and proteinuria in chronic kidney diseases. Elevated levels of saturated free fatty acid (FFA) are harmful to various tissues, implemented in the progression of diabetes and its complications such as proteinuria in diabetic nephropathy. Here, we investigated the molecular mechanism of palmitate cytotoxicity in cultured mouse podocytes. Incubation with palmitate dose-dependently increased cytosolic and mitochondrial reactive oxygen species, depolarized the mitochondrial membrane potential, impaired ATP synthesis and elicited apoptotic cell death. Palmitate not only evoked mitochondrial fragmentation but also caused marked dilation of the endoplasmic reticulum (ER). Consistently, palmitate upregulated ER stress proteins, oligomerized stromal interaction molecule 1 (STIM1) in the subplasmalemmal ER membrane, abolished the cyclopiazonic acid-induced cytosolic Ca(2+) increase due to depletion of luminal ER Ca(2+). Palmitate-induced ER Ca(2+) depletion and cytotoxicity were blocked by a selective inhibitor of the fatty-acid transporter FAT/CD36. Loss of the ER Ca(2+) pool induced by palmitate was reverted by the phospholipase C (PLC) inhibitor edelfosine. Palmitate-dependent activation of PLC was further demonstrated by following cytosolic translocation of the pleckstrin homology domain of PLC in palmitate-treated podocytes. An inhibitor of diacylglycerol (DAG) kinase, which elevates cytosolic DAG, strongly promoted ER Ca(2+) depletion by low-dose palmitate. GF109203X, a PKC inhibitor, partially prevented palmitate-induced ER Ca(2+) loss. Remarkably, the mitochondrial antioxidant mitoTEMPO inhibited palmitate-induced PLC activation, ER Ca(2+) depletion and cytotoxicity. Palmitate elicited cytoskeletal changes in podocytes and increased albumin permeability, which was also blocked by mitoTEMPO. These data suggest that oxidative stress caused by saturated FFA leads to mitochondrial dysfunction and ER Ca(2+) depletion through FAT/CD36 and PLC signaling, possibly contributing to podocyte injury.

Background parenchymal enhancement on breast MRI and mammographic breast density: correlation with tumour characteristics.

AIM: To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. MATERIALS AND METHODS: A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. RESULTS: At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p=0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogen-receptor (ER)-positive breast cancer (p=0.045) and progesterone receptor (PR)-positive breast cancer (p=0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p=0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (+)/HER2 (-) cancer (OR=0.231, 95% CI: 0.070, 0.760; p=0.016). No association between the histological tumour characteristics and BPE was observed. CONCLUSION: In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics.

Ultra-thin strut cobalt chromium bare metal stent usage in a complex real-world setting. (SOLSTICE registry).

AIM: To report clinical follow-up at 6 months after implantation of the ultra-thin strut cobalt chromium SolarFlex stent in a real-world setting. METHODS AND RESULTS: Patients (n = 240) with single or multiple vessel coronary artery disease undergoing percutaneous coronary intervention (PCI) at four sites in Europe were enrolled in the SOLSTICE (SolarFlex Stent in Routine Clinical Practice) registry. Follow-up at 6 months was 100 %. Diabetes was present in 29 % of the patients, 30 % presented with acute myocardial infarction and 17 % had unstable angina. Of the patients, 27 % had previously undergone PCI or coronary artery bypass surgery. Lesion complexity was high (50 % B2 + C type lesions). Device success was achieved in 99.7 % of cases and the major adverse cardiac event (MACE) rate was 5.8 % at 6 months of follow-up. Target lesion revascularisation (TLR) was 5.0 % at 6 months. CONCLUSIONS: The SOLSTICE registry showed that in a complex real-world setting the SolarFlex bare metal stent, with ultra-thin struts and customised scaffolding, provided low clinical MACE and TLR rates. These results provide support for the use of the latest generation bare metal stent in contemporary European practice.

LAMC2 enhances the metastatic potential of lung adenocarcinoma.

Lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. However, mechanisms underlying the development of lung cancer metastasis remain unknown. Using genome-wide transcriptional analysis in an experimental metastasis model, we identified laminin γ2 (LAMC2), an epithelial basement membrane protein, to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration and invasion via EMT that was integrin ß1- and ZEB1-dependent. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung adenocarcinoma via EMT and may be a potential therapeutic target.

The impact of drug-resistant cytomegalovirus in pediatric allogeneic hematopoietic cell transplant recipients: a prospective monitoring of UL97 and UL54 gene mutations.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients. METHODS: Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up. RESULTS: In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively. CONCLUSION: This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.

Estimated long-term dietary exposure to lead, cadmium, and mercury in young Korean children.

BACKGROUND: Controlling for day-to-day variation is a key issue in estimating long-term dietary exposure to heavy metals using 24-hour recall (24HR) data from a relatively small number of days. OBJECTIVES: This study was conducted to estimate long-term dietary exposure to lead, cadmium and mercury among Korean children using the Iowa State University (ISU) method and to assess the contributions of different food groups to heavy metal intake. METHODS: We analyzed 2 days of 24HR data from 457 children between 0 and 6 years of age in 2010. Using bootstrapped concentration data for 118 representative foods, 93.5% of total intake was included in the exposure estimates in this study. Using the 2-day exposure data, we estimated long-term exposure by controlling for within-individual variation using the ISU method. RESULTS: The long-term dietary exposure estimates (mean±standard deviation) for lead, cadmium, and mercury were 0.47±0.14, 0.38±0.20, and 0.22±0.08 µg/kg bw/day, respectively. For lead and cadmium, the percentages of children whose exposure was greater than the reference value were 35 and 42%, respectively. Fruits were an important source of lead exposure, and cereal and fish and shellfish made the greatest contributions to the total cadmium and mercury exposure. CONCLUSIONS: Our findings also suggest that the long-term exposure to lead and cadmium was somewhat greater than the reference values, whereas mercury exposure was well below than the reference value in this population. Further studies may be necessary to evaluate the food items contributing to heavy metal exposure, and continuous monitoring is needed to ensure the safety of food intake and dietary patterns among vulnerable groups in Korea.

Differences in the HbA1c-lowering efficacy of glucagon-like peptide-1 analogues between Asians and non-Asians: a systematic review and meta-analysis.

AIMS: To compare the HbA1c-lowering efficacy of glucagon-like peptide-1 (GLP-1) analogues between Asians and non-Asians with type 2 diabetes. METHODS: We searched randomized controlled trials from MEDLINE, EMBASE, LILACS, CENTRAL and ClinicalTrials.gov. Studies described in English were included if the treatment duration was 12 weeks or more, information about ethnicity and baseline HbA1c values were available and a GLP-1 analogue was compared with a placebo. For the ethnic comparison, we divided the studies into Asian-dominant studies (≥ 50% Asian participants) and non-Asian-dominant studies (<50% Asian participants). RESULTS: Among the 837 searched studies, 15 trials were included for the meta-analysis. The weighted mean difference of HbA1c with GLP-1 analogues was -1.16% [95% confidence interval (CI) -1.48, -0.85] in the Asian-dominant studies and -0.83% (95% CI -0.97, -0.70) in the non-Asian-dominant studies. The between-group difference was -0.32% (95% CI -0.64, -0.01; p = 0.04). The relative risk (RR) with 95% CIs for achieving the target HbA1c ≤ 7.0% tended to be greater in the Asian-dominant studies [RR 5.7 (3.8, 8.7)] than in the non-Asian-dominant studies [RR 2.8 (2.4, 3.3)]. Body weight changes were similar between the two groups. Hypoglycaemia tended to be more common in Asian-dominant studies (RR 2.8 [2.3, 3.5]) than in non-Asian-dominant studies (RR 1.5 [1.2, 1.8]), but severe hypoglycaemia was very rare in both groups. CONCLUSION: GLP-1 analogues lower HbA1c more in Asian-dominant studies than in non-Asian-dominant studies. Further studies are warranted to explore the potential mechanisms of the ethnic difference.

HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small cell lung cancer.

Small cell lung cancer (SCLC) at advanced stage is considered an incurable disease. Despite good response to initial chemotherapy, the responses in SCLC patients with metastatic disease are of short duration and resistance inevitably occurs. Although several target-specific drugs have altered the paradigm of treatment for many other cancers, we have yet to witness a revolution of the same magnitude in SCLC treatment. Anthracyclines, such as doxorubicin, have definite activity in this disease, and ganetespib has shown promising activity in preclinical models but underwhelming activity as a single agent in SCLC patients. Using SCLC cell lines, we demonstrated that ganetespib (IC50: 31 nM) was much more potent than 17-allylamino-17-demethoxygeldanamycin (17-AAG), a geldanamycin derivative (IC50: 16 µM). Ganetespib inhibited SCLC cell growth via induction of persistent G2/M arrest and Caspase 3-dependent cell death. MTS assay revealed that ganetespib synergized with both doxorubicin and etoposide, two topoisomerase II inhibitors commonly used in SCLC chemotherapy. Expression of receptor-interacting serine/threonine-protein kinase 1 (RIP1), a protein that may function as a pro-survival scaffold protein or a pro-death kinase in TNFR1-activated cells, was induced by doxorubicin and downregulated by ganetespib. Depletion of RIP1 by either RIP1 small interfering RNA (siRNA) or ganetespib sensitized doxorubicin-induced cell death, suggesting that RIP1 may promote survival in doxorubicin-treated cells and that ganetespib may synergize with doxorubicin in part through the downregulation of RIP1. In comparison to ganetespib or doxorubicin alone, the ganetespib+doxorubicin combination caused significantly more growth regression and death of human SCLC xenografts in immunocompromised mice. We conclude that ganetespib and doxorubicin combination exhibits significant synergy and is efficacious in inhibiting SCLC growth in vitro and in mouse xenograft models. Our preclinical study suggests that ganetespib and doxorubicin combination therapy may be an effective strategy for SCLC treatment, which warrants clinical testing.

Xanthohumol inhibits cellular proliferation in a breast cancer cell line (MDA-MB231) through an intrinsic mitochondrial-dependent pathway.

AIMS: Xanthohumol isolated from hops has been reported to exhibit anticancer effects in diverse human cancers. However, its effect on breast cancer has not yet been clearly defined. The purpose of this study was to investigate the effects of xanthohumol on breast cancer cell proliferation. MATERIALS AND METHODS: After treatment with 5 µM, 10 µM, and 20 µM xanthohumol for 48 h, cells from the human breast cancer cell line MDA-MB-231 were studied using colony assay, flow cytometry, and western blotting. RESULTS: The survival rate of the MDA-MB231 cells treated with 10 µM and 20 µM xanthohumol for 48 h decreased significantly by 64.7 ± 1.8% and 40.1 ± 1.8%, respectively. The numbers of SubG0/G1 cells in the group treated with 10 µM and 20 µM xanthohumol increased significantly to 11.3 ± 0.2 and 18.4 ± 0.1, respectively. A ladder pattern of DNA fragmentation was also observed. Xanthohumol increased the expression of Bax in the mitochondria, which correspondingly decreased in the cytoplasm. The activity of caspase-3 and caspase-9 was shown to increase significantly in the treated groups but not in the control group. CONCLUSIONS: Xanthohumol inhibited the proliferation of MDA-MB-231 cells through a mitochondria- and caspase-dependent apoptotic pathway. This result suggests that xanthohumol might serve as a novel therapeutic drug for breast cancer.

Predictors of renal relapse in Korean patients with lupus nephritis who achieved remission six months following induction therapy.

Renal relapse in patients with lupus nephritis (LN) is a risk factor for poor renal function. Therefore, there is a need to identify clinical and serological risk factors for renal relapse. A total of 108 patients with LN were enrolled in this study. All the subjects had achieved complete remission or partial remission following six months of induction therapy. We retrospectively analyzed their clinical and laboratory indices, final renal function, and kidney biopsy findings. The median follow-up period after LN diagnosis was 81 months. Renal relapse had occurred in 36 patients; it occurred in 38% and 46% of patients within five and 10 years after achievement of renal remission, respectively. There was no difference between the relapsed rate in patients with complete remission and that in those with partial remission. Clinical variables at LN onset and renal biopsy findings in the patients with sustained remission and relapsed patients were also not different. The probability of renal relapse was significantly higher in patients with an earlier age of onset of systemic lupus erythematosus (SLE) (≤ 28 years versus >28 years; HR 7.308, P=0.001), seronegativity for anti-Ro antibody (seronegativity versus seropositivity; HR 3.514, P=0.007), and seropositivity for anti-dsDNA antibody at six months after initiation of induction therapy (HR 8.269, P=0.001). Our study demonstrated that early onset of SLE, seronegativity for anti-Ro antibody and increased anti-dsDNA antibody following six months of induction therapy independently predict renal relapse among the LN patients.

Effect of Lactobacillus plantarum CJLP243 on the growth performance and cytokine response of weaning pigs challenged with enterotoxigenic Escherichia coli.

The purpose of the present study was to evaluate the effect of diets containing Lactobacillus plantarum CJLP243 on the growth and cytokine response of weaning pigs (Sus scrofa) challenged with enterotoxigenic Escherichia coli (ETEC). In a 28-d experiment (14 d before and 14 d after challenge), a total of 108 pigs at 20 ± 1 d of age were allotted to 1 of 6 diets. These were a control diet without ETEC challenge (CON) and 5 treatment diets with ETEC challenge, including a control diet with ETEC challenge (negative control, NC); a positive control diet containing antibiotics (PC); control diet plus (10(8), 10(9), or 10(10)) cfu/kg L. plantarum CJLP243 (T1, T2, and T3, respectively). After challenge, NC showed the least ADFI, whereas PC and T3 had the greatest ADFI (P = 0.002). The ADG of PC, T2, and T3 were greater (P = 0.001) than that of CON, NC, and T1 during wk 1 to wk 2. During wk 3 to wk 4, a marked decline was seen in NC (P = 0.001) compared with CON, whereas PC and T3 showed increased ADG (P = 0.001). The overall ADG of PC and T3 were greater (P < 0.001) than the remaining groups. The PC and T3 had the greatest G:F during the second 2 wk (P = 0.002), and the overall 4-wk experimental period (P = 0.003). At 3 h after challenge, all groups except CON had greater rectal temperatures (RT; P < 0.05). The RT decreased to prechallenge temperatures at 9 h (PC and T3), 24 h (T1 and T2), and remained increased until d 7 in NC. At 7 and 14 d postinfection, the number of animals detected positive for ETEC by PCR assay was the greatest in NC; however, the PC group had the fewest ETEC-positive animals (P < 0.05), which was similar to T3. All challenged pigs, except T2, had greater concentrations of serum haptoglobin compared with CON, with the greatest concentration observed in NC (P < 0.001). Challenged pigs had increased serum concentrations of tumor necrosis factor alpha (TNF-α) 3 to 48 h postinfection, with the greatest concentration of TNF-α at 48 h observed in NC (P < 0.05). Similarly, greater (P < 0.05) serum concentrations of interferon-γ were observed for 9 h (T1 and T3), 24 h (T2 and PC), and 48 h (NC) postinfection. The serum concentration of IL-6 increased (P < 0.05) for 3 h in T3 and 24 h in NC. In conclusion, our findings suggest that L. plantarum CJLP243, at a concentration of 10(10) cfu/kg, may serve as a potential alternative to antibiotic supplementation to improve the growth and health performance of weaning pigs, especially during acute inflammation of the gut after bacterial infections.