Aumento de la lipocalina orosomucoide-1 (ORM1) en sujetos con hiperaldosteronismo primario / Increase of lipocalin ORM1 in primary aldosteronism

El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.

Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.

Inflammatory markers in palatine tonsils of children with obstructive sleep apnea syndrome / Marcadores inflamatórios em tonsilas palatinas de crianças com síndrome da apneia obstrutiva do sono

Abstract Introduction Obstrutive sleep apnea syndrome is characterized by repeated episodes of upper airway obstruction, associated with intermittent hypoxia and hypercapnia, and the main risk factor in childhood is adenotonsillar hypertrophy. The lymphocytes in these structures are responsible for local and systemic immune responses. Objective Verify the levels of the inflammatory markers, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, CRP and α1-GP, in the tonsils of children with and without obstructive sleep apnea syndrome. Methods This cross-sectional prospective study included 34 children with complains of snoring, difficulty breathing during sleep or recurrent tonsillitis. Patients underwent to a complete otorhinolaryngological examination, nasal endoscopy and polysomnography and were divided into two groups with 17 children each: obstructive sleep apnea syndrome group and control group. All underwent an adenotonsillectomy. Cytokines were measured in the collected tonsils (ELISA and Multiplex methods). Results Statistically significant increasing were observed between IL-8 and IL-10 cytokines of patients with obstructive sleep apnea when compared to the control group; also between c-reactive protein and α1-GP of the tonsils cortical region in children with obstructive sleep apnea syndrome when compared with the medullary region. There were no statistically significant differences for the remaining inflammatory mediators. Conclusion After the analysis of the levels of pro and anti-inflammatory markers (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, CRP, α1-GP) in the tonsils, we observed higher levels of markers IL-8 and IL-10 in pediatric patients with obstructive sleep apnea syndrome.

Resumo Introdução A síndrome da apneia obstrutiva do sono é caracterizada por episódios repetidos de obstrução das vias aéreas superiores, associados a hipóxia intermitente e hipercapnia, e o principal fator de risco na infância é a hipertrofia adenotonsilar. Os linfócitos nessas estruturas são responsáveis por respostas imunes locais e sistêmicas. Objetivo Dosar os marcadores inflamatórios, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, PCR e α1-GP, nas tonsilas de crianças com e sem síndrome da apneia obstrutiva do sono. Método Estudamos prospectivamente 34 crianças que se queixavam de ronco, dificuldade para respirar durante o sono ou tonsilites recorrentes. Os pacientes foram submetidos a exame otorrinolaringológico completo, endoscopia nasal e polissonografia e foram divididos em dois grupos com 17 crianças cada: síndrome de apneia obstrutiva do sono e controle. Todos foram submetidos à adenotonsilectomia. As citocinas foram medidas nas tonsilas coletadas (métodos ELISA e Multiplex). Resultados Com diferenças estatisticamente significantes, observou-se aumento das citocinas IL-8 e IL-10 em pacientes com apneia obstrutiva do sono em comparação ao grupo controle, assim como aumento dos níveis de proteína C reativa e de α1-GP na região cortical das tonsilas de crianças portadoras de síndrome da apneia obstrutiva do sono em comparação com a região medular. Não houve diferenças estatisticamente significantes para o restante dos mediadores inflamatórios. Conclusão Após a análise dos níveis de marcadores pró e anti-inflamatórios (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, PCR, α1-GP) nas tonsilas, observamos níveis mais altos de marcadores IL-8 e IL-10 em pacientes pediátricos com síndrome da apneia obstrutiva do sono.

Adiposity, inflammation and fat-soluble vitamins in adolescents / Adiposidade, inflamação e vitaminas lipossolúveis em adolescentes

Abstract Objective: Evaluate the association between inflammatory process, adiposity, and vitamins A, D, and E in adolescents, according to gender. Methods: Cross-sectional study with adolescents aged 12-19 years old of both genders attending public schools in Recife. A questionnaire was used to collect data on socioeconomic level, lifestyle, and food intake of adolescents. Then, an anthropometric evaluation and a blood sampling were performed to analyze serum concentrations of α-1-acid glycoprotein, retinol, β-carotene, α-tocopherol, and 25-hydroxy-vitamin D. Results: The levels of α-1-acid glycoprotein were higher for abdominal obesity in both genders. Male adolescents with insufficient serum α-tocopherol levels had low levels of α-1-acid glycoprotein (p = 0.03) and an increased risk of 25-hydroxy-vitamin D and β-carotene deficiency in relation to total and abdominal fat; female adolescents had an increased risk of insufficient β-carotene with abdominal obesity (PR: 1.33; 95% CI: 1.2-1.5). Conclusion: Abdominal adiposity implies a higher risk of inflammation and causes different changes to the levels of fat-soluble vitamins according to gender.

Resumo: Objetivo: Avaliar a associação entre processo inflamatório, adiposidade e as vitaminas A, D e E em adolescentes, segundo o sexo. Métodos: Estudo transversal com adolescentes de 12 a 19 anos de ambos os sexos de escolas públicas de Recife. Foi utilizado um questionário para coleta de dados socioeconômicos, de estilo de vida e de consumo alimentar dos adolescentes. Em seguida, realizou-se a avalição antropométrica e coleta de sangue para análise das concentrações séricas de α-1-glicoproteína ácida, retinol, β-caroteno, α-tocoferol e 25-hidroxivitamina D. Resultados: Os níveis de α-1-glicoproteína ácida foram maiores na obesidade abdominal de ambos os sexos. Os meninos com níveis séricos insuficientes de α-tocoferol expressaram níveis reduzidos de α-1-glicoproteína ácida (p = 0,03) e apresentaram um maior risco de deficiência de 25-hidroxivitamina D e β-caroteno na adiposidade total e abdominal, enquanto as meninas mostraram maior risco de insuficiência de β-caroteno com a obesidade abdominal (RP 1,33; IC 95% 1,2-1,5). Conclusão: A adiposidade abdominal reflete maior risco de inflamação e causa alterações distintas nas concentrações das vitaminas lipossolúveis, de acordo com o sexo.

LC-MS/MS-based screening of new protein biomarkers for cervical precancerous lesions and cervical cancer / 南方医科大学学报

OBJECTIVE@#To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions.@*METHODS@#Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms.@*RESULTS@#Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway.@*CONCLUSIONS@#We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.

Associations among body composition, inflammatory profile and disease extent in ulcerative colitis patients / Associações entre composição corporal, perfil inflamatório e extensão da doença em pacientes com retocolite ulcerativa

Summary Objective: The aim of our study was to assess body composition status and its association with inflammatory profile and extent of intestinal damage in ulcerative colitis patients during clinical remission. Method: This is a cross-sectional study in which body composition data (phase angle [PhA], fat mass [FM], triceps skin fold thickness [TSFt], mid-arm circumference [MAC], mid-arm muscle circumference [MAMC], adductor pollicis muscle thickness [APMt]), inflammatory profile (C-reactive protein [CRP], a1-acid glycoprotein, erythrocyte sedimentation rate [ESR]) and disease extent were recorded. Results: The mean age of the 59 patients was 48.1 years; 53.3% were women. Most patients were in clinical remission (94.9%) and 3.4% was malnourished according to body mass index. PhA was inversely correlated with inflammatory markers such as CRP (R=-0.59; p<0.001) and ESR (R=-0.46; p<0.001) and directly correlated with lean mass: MAMC (R=0.31; p=0.01) and APMt (R=0.47; p<0.001). Lean mass was inversely correlated with non-specific inflammation marker (APMt vs. ESR) and directly correlated with hemoglobin values (MAMC vs. hemoglobin). Logistic regression analysis revealed that body cell mass was associated with disease extent (OR 0.92; 95CI 0.87-0.97; p<0.01). Conclusion: PhA was inversely correlated with inflammatory markers and directly correlated with lean mass. Acute inflammatory markers were correlated with disease extent. Body cell mass was associated with disease extent.

Resumo Objetivo: Avaliar a composição corporal de pacientes portadores de retocolite ulcerativa em remissão clínica e sua associação com o perfil inflamatório e a extensão da lesão intestinal. Método: Foi realizado um estudo transversal. Os dados relacionados à composição corporal foram ângulo de fase (AF), massa adiposa (MA), dobra cutânea triciptal (DCT), circunferência do braço (CB), circunferência muscular do braço (CMB) e espessura do músculo adutor do polegar (EMAP). O perfil inflamatório foi avaliado através da dosagem da proteína-C reativa (PCR), a1-glicoproteína ácida e velocidade de hemossedimentação (VHS) e a extensão da doença foi avaliada de acordo com o exame endoscópico. Resultados: Foram avaliados 59 pacientes. A média de idade foi de 48,1 anos e 53,3% eram mulheres. A maioria dos pacientes (94,9%) estava em remissão clínica da doença e 3,4% foi classificada como desnutrida de acordo com o IMC. Observou-se uma correlação inversa entre AF e marcadores inflamatórios como a PCR (R=-0,59; p<0,001) e VHS (R=-0,46; p<0,001) e uma correlação direta entre AF e os indicadores de massa magra como CMB (R=0,31; p=0,01) e EMAP (R=0,47; p<0,001). A massa magra foi inversamente correlacionada com marcadores inflamatórios não específicos, como a VHS, e diretamente correlacionada com a hemoglobina. De acordo com a análise de regressão logística, a massa celular corporal foi associada com extensão da lesão intestinal (OR 0,92; IC95% 0,87-0,97; p<0,01). Conclusão: AF foi inversamente correlacionado com marcadores inflamatórios e diretamente correlacionado com a massa magra. Marcadores inflamatórios de fase aguda e massa celular corporal foram correlacionados com extensão da lesão intestinal.

Serum concentrations of acute phase proteins in goats and ewes with naturally acquired Staphylococcus aureus mastitis / Concentração de proteínas de fase aguda em cabras e ovelhas com mastite de ocorrência natural causada por Staphylococcus aureus

Serum protein concentrations, including acute phase proteins (APPs), of goats and ewes with naturally acquired Sthaphylococcus aureus mastitis were determined by means of SDS-PAGE electrophoresis to evaluate the relevance of these APPs as biomarkers of the disease in these species. Fifteen healthy goats and 5 goats with naturally acquired staphylococci mastitis, as well as fifteen healthy ewes and 5 ewes with staphylococci mastitis were submitted to daily blood sampling during 7 days. In goats, an increase of 570%, 125%, 621%, and 279% in serum concentrations of ceruloplasmin, fibrinogen, haptoglobin and α1-acid glycoprotein, respectively, was observed. In sheep the increase in serum concentrations of ceruloplasmin, fibrinogen, haptoglobin and α1-acid glycoprotein was of 337%, 90%, 461%, and 225%, respectively. Our results indicate that these APPs have considerable potencial as early and sensible biomarkers of mastitis caused by S. aureus in goats and sheep.(AU)

O proteinograma, incluindo proteínas de fase aguda (PFAs), de cabras e ovelhas com mastite de origem natural causada por Staphylococcus aureus, foi determinado por meio de eletroforese em gel de poliacrilamida contendo dodecil sulfato de sódio (SDS-PAGE) a fim de avaliar a importância destas PFAs como biomarcadores da enfermidade nestas espécies. Amostras de sangue foram colhidas diariamente de cinco cabras e cinco ovelhas com mastite estafilocócica naturalmente adquirida, bem como de quinze cabras e quinzes ovelhas saudáveis durante 6 dias consecutivos. Nas fêmeas caprinas, foi verificado aumento dos teores séricos de ceruloplasmina (570%), fibrinogênio (125%), haptoglobina (621%), e α1-glicoproteína ácida (279%). Nas fêmeas ovinas as concentrações de ceruloplasmina, fibrinogênio, haptoglobina e α1-glicoproteína ácida elevaram-se em 337%, 90,9%, 461% e 225%, respectivamente. Os resultados permitem inferir que estas PFAs são marcadores sensíveis e precoces de mastite causada por S. aureus em cabras e ovelhas.(AU)

Proteinograma sérico de éguas com placentite ascendente e seus respectivos neonatos: dados preliminares / Serum protein concentrationin mares with ascending placentitis and their newborns: preliminary data

Este estudo teve por objetivo estabelecer o proteinograma sérico em éguas com placentite induzida e em seus respectivos neonatos. Foram coletadas amostras de sangue das éguas em oito momentos diferentes e dos potros em quatro momentos. Para obtenção da concentração das frações proteicas, utilizou-se eletroforese em gel de acrilaminada contendo dodecil sulfato de sódio (SDS-PAGE). No método utilizado, foram observadas 23 bandas proteicas, cujos pesos moleculares variaram de 16KDa a 245KDa, sendo possível a identificação das seguintes frações: 175KDa, 102KDa, 83KDa, 63KDa, 50KDa, 41KDa, 39KDa e 28KDa. De todas as bandas proteicas encontradas, somente as de 39KDa e 41KDa apresentaram alteração na cinética nos momentos avaliados. De acordo com a solução marcadora, pode-se sugerir que essas proteínas seriam alfa1-glicoproteína ácida (39KDa) e haptoglobina (41KDa). A concentração de imunoglobulinas nos potros apresentou aumento significativo a partir das 12 horas de nascimento. Não está elucidado se estes níveis refletem a persistência do processo inflamatório placentário ou se são alterações fisiológicas do periparto. Não foram observadas alterações na cinética das proteínas nos potros nas primeiras 48 horas.(AU)

The aim of this paper was to identify the serum acute phase protein concentration in mares with induced placentitis and their neonates. Blood samples were collected from the mares in 8 different moments, and from the foals, in 4 moments. To obtain the concentration of protein fractions acrilaminada gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE) was used. In the used method 23 protein bands whose molecular weights ranged from 16kDa to 245kDa were observed, it is possible to identify the following fractions: 175kDa, 102kDa, 83kDa, 63kDa, 50kDa, 41kDa, 39kDa and 28kDa. Of all the protein bands found only the 39KDa and 41KDa have changes in the kinetics in the evaluated times. According to the marker solution, we would suggest that these proteins are alfa1-acid glycoprotein (39kDa) and haptoglobin (41kDa). The concentration of immunoglobulins in foals increased significantly from 12 hours of birth.(AU)

Identification of novel urinary biomarkers for assessing disease activity and prognosis of rheumatoid arthritis

To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates—gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)—in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals.

Decreased levels of alpha-1-acid glycoprotein are related to the mortality of septic patients in the emergency department

OBJECTIVE: To determine the validity of alpha-1-acid glycoprotein as a novel biomarker for mortality in patients with severe sepsis. METHODS: We prospectively included patients with severe sepsis or septic shock at the emergency department at a single tertiary referral teaching hospital. All of the patients were enrolled within the first 24 hours of emergency department admission, and clinical data and blood samples were obtained. As the primary outcome, we investigated the association of serum levels of alpha-1-acid glycoprotein and 96-hour mortality with logistic regression analysis and generalized estimating equations adjusted for age, sex, shock status and Acute Physiology and Chronic Health Evaluation II score. RESULTS: Patients with septic shock had lower alpha-1-acid glycoprotein levels at the time of emergency department admission compared to patients without shock (respectively, 149.1 ±42.7 vs. 189.8 ±68.6; p = 0.005). Similarly, non-survivors in the first 96 hours were also characterized by lower levels of alpha-1-acid glycoprotein at the time of emergency department admission compared to survivors (respectively, 132.18 ±50.2 vs. 179.8 ±61.4; p = 0.01). In an adjusted analysis, alpha-1-acid glycoprotein levels ≤120 mg/dL were significantly associated with 96-hour mortality (odds ratio = 14.37; 95% confidence interval = 1.58 to 130.21). CONCLUSION: Septic shock patients exhibited lower circulating alpha-1-acid glycoprotein levels than patients without shock. Alpha-1-acid glycoprotein levels were independently associated with 96-hour mortality in individuals with severe sepsis. .

preliminary study of inflammatory markers in non-alcoholic steatohepatitis patients

It was reported that C-reactive protein [CRP] levels increase in parallel with the progression of chronic liver diseases, such as chronic hepatitis and liver cirrhosis. Inflammatory markers, such as high sensitive C-reactive protein [hsCRP], ferritin, transferrin, albumin, alpha-1 acid glycoprotein [AAG], alpha-2 macroglobulin [AMG], alpha-1 anti-trypsin [AAT] and lipoprotein a [Lp[alpha]] were measured in coronary artery disease patients [CAD] and CAD patients with non-alcoholic steatohepatitis [NASH]. In the present preliminary study an attempt was made to study whether there is an increase in the levels of CRP in CAD patients associated with NASH. CAD patients showed an increase in CRP and serum ferritin levels. In CAD patients with NASH along with an increase in the levels of serum ferittin [p<0.001], the levels of serum AMG and ceruloplasmin [CP] were also increased [p<0.01]. The CAD patients with NASH had a higher proportion of diabetes, hypertension and dyslipidaemia compared to CAD patients. But how this difference contributes to the elevation in acute inflammatory markers particularly AMG and CP levels in CAD patients with NASH cannot be explained. This study shows that a substantial number of CAD patients may be associated with NASH. Non-invasive simple parameters that reflect the degree of inflammation and fibrosis of the liver in patients with NASH would facilitate improved understanding and treatment of the disease. Further studies may be necessary to evaluate the percentage of NASH patients progressing to CAD

Effect of minimally invasive Ivor-Lewis esophagectomy on acute phase responses in patients with esophageal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effect of minimally invasive Ivor-Lewis esophagectomy on acute phase responses in patients with esophageal carcinoma.</p><p><b>METHODS</b>Forty-eight patients with middle or low thoracic esophageal carcinoma underwent Ivor-Lewis esophagectomy. The patients were divided into small incision group (n = 25) and conventional group (n = 23) according to the patients' will. Serum levels of acute phase proteins C reactive protein (CRP), haptoglobin (HPT), α₁-acid glycoprotein (α₁-AG), ceruloplasmin (CER), transferrin (TRF), β₂-microglobulin (β₂-MG), album protein (ALB), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were measured and compared on 1st day before operation, at 18 hours as well as 3rd and 7th day after operation.</p><p><b>RESULTS</b>There was no significant difference in all the acute phase proteins indicators and IL-6 between the small incision and conventional groups at each time points after operation (P > 0.05). In both groups the levels of CRP, α₁-AG and HPT were significantly higher after operation than before operation (P < 0.05). The levels of ALB and TRF were significantly lower after operation than before operation (P < 0.05). The levels of CER and β₂-MG were not significantly different during perioperative period (P > 0.05). The level of TNF-α was significantly higher in the small incision group than that in the conventional group at the 18 hours postoperationally (P < 0.05), and were not significantly different on the other time points between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>Compared with conventional operation, the small incision Ivor-Lewis esophagectomy do not significantly alleviate the stress of the surgical trauma in patients. Unchanging the essence of operation, if one is trying to minimize the stress caused by surgery on patients, the key factor is not the size of incision. An effective approach should be found in other operation-related factors.</p>

Relationship between periodontitis and rheumatoid arthritis and the effect of non-surgical periodontal treatment

This study analyzed the association of periodontal disease (PD) and rheumatoid arthritis (RA). Seventy-five 35-60-year-old patients were assigned to 5 groups according to the presence (+) or not (-) of PD and RA and the treatment received (TR+) or not (TR-) for PD. Group 3 uses total prosthesis (TP). Clinical and laboratory evaluations were performed at baseline, 3 and 6 months of follow-up by probing pocket depth, bleeding on probing and plaque index for PD, HAQ, DAS28, SF-36 and laboratory: AAG, ESR, CRP for RA. Statistically significant differences for PD after 3 (p=0.0055) and after 6 months (p=0.0066) were obtained in Group 1 (RA+PD+TR+) and 2(RA+PD+TR-); significant reduction in the percent of BOP after 6 months (p=0.0128) and significant reduction in the percent of Pl after 3 (p=0.0128) and 6 months (p=0.0002) in Group 1. Statistically significant differences between Groups 1 and 3 (RA+TP) for DAS28 at baseline and after 3 months were observed, but not after 6 months. No other parameters for RA were significantly affected. The relationship between RA and PD disease activities is not clear, but the importance of periodontal treatment in the control of inflammation to avoid tooth extraction is evident.

Este estudo avaliou a influência da doença periodontal (DP) na artrite reumatóide (AR). 75 pacientes, 35-60 anos, divididos em 5 Grupos, considerando a situação sistêmica e periodontal foram analisados. Um Grupo usava prótese total (PT). Os parâmetros clínicos e laboratoriais analisados: inicial, 3 e 6 meses receberam tratamento estatístico. As correlações entre as reduções da profundidade de sondagem, placa microbiana e sangramento à sondagem com as de Alfa 1, PCR, VHS e exames de qualidade de vida (HAQ, DAS28, SF36) foram também analisadas. Comparando o Grupo 1 (AR+DP+TR+) e Grupo 2 (AR+DP+TR-), aqueles que receberam tratamento periodontal não-cirúrgico (TPNC) tiveram reduções estatisticamente significativas em relação a PS aos 3 meses (p=0,0055) e 6 meses (p=0,0066); as reduções da por cento SS foram estatisticamente significantes aos 6 meses (p=0,0128) e da por cento PM aos 3 (p=0,0128) e 6 meses (p=0,0002). O TPNC não apresentou correlação com a melhora dos exames laboratoriais, nem com os exames de qualidade de vida. Comparando o Grupo 1 com o Grupo 3 (AR+PT) houve diferença estatisticamente significante no DAS28 inicial e 3 meses. Não foi possível verificar uma correlação direta do TPNC na atividade da doença sistêmica, mas pode-se constatar a sua importância, evitando a extração múltipla dos dentes.

Pharmacokinetics and plasma protein binding of rutin deca (H-) sulfate sodium / 药学学报

Rutin deca (H-) sulfate sodium (RDS) possesses very good activity as an inhibitor of the complement system of warm-blooded animals and HIV. An ion-pair coupled with solid-phase extraction technique (IP-SPE) was developed to extract RDS from rat plasma, urine, bile and protein solution samples. The assay was applied to pharmacokinetics of RDS, including plasma pharmacokinetics, excretion and protein binding studies. After i.v. 5, 20 and 100 mg x kg(-1) RDS via tail vein in rats, the plasma concentration-time profiles were fitted using 3P97 software. The average terminal half-life (t(1/2)) was 3.432 +/- 0.185 2 h. The relationship of dose and AUC of RDS was linear within the dosage range. This suggested that the disposition of RDS in rats belong to linear kinetics and the pharmacokinetic parameters of RDS were dose independent. After iv RDS 20 mg x kg(-1) in rats, the biliary excretion amount of parent drug amount was only 0.3181% +/- 0.2087% of given dosage, and the urinary excretion was 86.0% +/- 6.1% in 36 h. Ultrafiltration techniques were applied to determine the protein binding of RDS in plasma (from SD rat, Beagle dog and human), human serum albumin (HSA) and human alpha1-acid glycoprotein (AGP). The mean protein binding rate in plasma of SD rat, Beagle dog and human plasma of RDS were 80%-90%, in which the range of concentration of RDS was 5 to 100 microg x mL(-1). The protein binding to HSA was 85.7% +/- 1.3% and 14.0% +/- 3.2% to AGP.

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristicsof two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restrited fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype(P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

Methodology of electrospray ion trap mass spectrometry for analyzing the non-covalent binding of protein and low-molecular-weight ligand / 药学学报

A new MS-titration method for the non-covalent binding of protein-ligand based on the research of berberine and alpha1-acid glycoprotein was established. The major presumption of new method is that the total concentration of protein-ligand complex is approximately the same as the total concentration of acting protein if a certain extent of affinity is existed between protein and ligand, in addition, the mole amount of acting ligand is more than that of acting protein. The non-covalent binding behaviours between berberine and alpha1-acid glycoprotein was studied by using electrospray ionization ion trap mass spectrometry (ESI-ITMS) , and the results were verified by fluorescence quenching method. The results showed that the binding behaviours between berberine and alpha1-acid glycoprotein, for example, stability constant, number of binding site, type of the main binding force, were almost the same by using the new MS-titration method and fluorescence quenching method. Comparing with the reported MS-titration method, the presented MS-titration method in this paper is more simple and applicable, does not demand much for the devices, and can lead to reliable results in same cases.

Influence of ORM1 polymorphism on serum concentration of free nortriptyline / 药学学报

To study the effect of alpha1-acid glycoprotein 1 (ORM1) polymorphism on the concentration of free nortriptyline in serum, genotyping analysis was employed in ORM1 by sequencing. Eighteen unrelated male adults were chosen and given a single dose of 25 mg nortriptyline orally, then the blood samples were taken at 0, 1, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96 and 168 hours after drug administration. Nortriptyline and 10-OH-nortriptyline in serum and ultrafiltrate were detected for the total and free concentration by using HPLC-MS/MS. Pharmacokinetic parameters were compared among different ORM1 genotypes. No significant differences were shown in the pharmacokinetic parameters of total nortriptyline and 10-OH-nortriptyline. The mean AUC(0-infinity) of free nortritpyline in ORM1 * F/ * F1 subjects was significantly higher than that in ORM1 * F1/ * S and ORM1 * S/ * S subjects [(119.1 +/- 74.4) ng x mL(-1) x h vs (51.4 +/- 23.2) ng x mL(-1) x h and (42.4 +/- 11.6) ng x mL(-1) x h]. The percentage of protein binding in subjects with ORM1 * F1/ * F1 genotype at 2, 3, 4, 6, 8 and 12 h after administration was slightly lower than in those with ORM1 * F1/ * S and ORM1 * S/ * S genotypes while the distinct difference was shown at 4 h (P < 0.05). Different ORM1 genotypes might affect the protein binding percentage and the concentration of serum free nortriptyline. The ability binding to the drug was higher in subjects with ORM1 * S/ * S genotype than in those with other two genotypes, so as to cause the lower concentration of free nortriptyline.

Assessment of nutritional status and prognosis in advanced metastatic cancer / 대한내과학회지

BACKGROUND: Depletion of nutritional reserves and significant weight loss can lead to an increased risk of morbidity, reduced chemotherapy response, and shorter survival in patients with cancer. Numerous methodologies are used for the assessment of nutritional status. However, it remains unclear which of these tools is the most appropriate in the setting of cancer chemotherapy. The PINI (prognostic inflammatory nutritional index) is a simple scoring system that has been used to evaluate nutritional status and prognosis in critically ill patients. The aim of this study was designed to investigate the relationship between nutritional status after the palliative chemotherapy and prognosis in advanced metastatic cancer. METHODS: This study included 130 patients with ECOG PS (Eastern Cooperative Oncology Group performance status) 1~3 in advanced metastatic cancer following the palliative chemotherapy. ECOG PS, body mass index, alpha 1-acid glycoprotein, C-reactive protein, albumin, prealbumin, transferrin, protein, lactate dehydrogenase, PINI ratio, and survival time were evaluated. RESULTS: In 130 patients, the median age was 57 years. The ECOG PS was 1 68 patients, 2 43, 3 19. The mean value of PINI was PS 1 16.0+/-47.8, PS 2 55.6+/-106.9, PS 3 106.3+/-141.6. The mean survival was PS 1 144.0+/-71.8, PS 2 68.9+/-41.2, PS 3 32.0+/-6.9 days. In the PS 3 group, the mean values of alpha 1-acid glycoprotein, C-reactive protein, and lactate dehydrogenase were significantly higher than in the PS 1 group. In the PS 3 group, the mean values of albumin, prealbumin, and transferrin were significantly lower than in the PS 1 group. The survival time was correlated with the ECOG PS (r=-0.602, p<0.001,), PINI (r=-0.318, p<0.001,), alpha 1-acid glycoprotein (r=-0.265, p=0.002), C-reactive protein (r=-0.345, p<0.001), albumin (r=0.324, p<0.001), prealbumin (r=0.260, p=0.003) and transferrin (r=0.277, p=0.001). CONCLUSIONS: The PINI may be a useful scoring system for the assessment of nutritional status and prognosis in advanced metastatic cancer following palliative chemotherapy, but the ECOG PS is most strong correlation with the survival time.

Proteomic analysis of urinary protein markers for accurate prediction of diabetic kidney disorder.

AIM OF THE STUDY: Microalbuminuria is currently the only diagnostic tool available for early diagnosis of diabetic nephropathy. The test is based on immunological detection of small quantities of albumin in the urinary samples of diabetes patients. There are several limitations of the use of microalbuminuria as an index of renal function. It is therefore desirable to identify additional protein markers that would augment prediction of diabetic nephropathy. The aim of this study is to identify urinary protein markers for specific and more accurate prediction of nephropathy in diabetes patients. DESIGN: 100 registered Type II diabetic patients were studied. Abundant proteins of microalbuminuria positive urinary samples of these patients were analyzed by proteomics approaches of 2-Dimentional Gel Electrophoresis (2DGE) and mass spectrometry. RESULTS: 2-DGE analysis of the urine sample revealed four main proteins along with albumin in these samples. These were zinc alpha-2 glycoprotein, alpha-1 acid glycoprotein, alpha-1 microglobulin and IgG as identified by Matrix Assisted Laser Desorption Ionization-Tune of Flight (MALDI-ToF) and by western blot. Twenty control samples and three cases with microalbuminuria negative to positive transition does suggest the early and co-appearance of the markers with albumin. We have also analyzed full length spectrum of these samples by MALDI-ToF. CONCLUSION: Our study shows the presence of additional proteins in urine samples of microalbuminuria positive diabetes patients. These proteins can be used as markers for specific and accurate clinical analysis of Diabetic nephropathy. We propose a mass spectrometry based high throughput diagnostic approach to detect these markers in the urine sample.

Study on the enantiomer separation of cetirizine dihydrochloride using proteinate- and amylose-based chiral stationary phase / 药学学报

<p><b>AIM</b>To study the chromatographic behavior of cetirizine dihydrochloride on the proteinate- and amylose- based chiral stationary phases so as to optimizate the chromatographic condition of its enantiomers separation.</p><p><b>METHODS</b>When using amylose-based, alpha1-acid glycoprotein and ovomucoid protein chiral stationary phase, the mobile phase was hexane-isopropyl alcohol-alcohol-trifluoroacetic acid (430:45:25:1), acetonitrile-10 mmol x L(-1) phosphate buffer solution (adjusted to pH 7.0 with sodium hydroxide) (4:96) and acetonitrile-20 mmol x L(-1) KH, PO4 solution (adjusted to pH 7.0 with triethylamine) (12.7:87.3), respectively. The temperature of proteinate column was 25 degrees C. The detective wavelength was 230 nm.</p><p><b>RESULTS</b>The two enantiomers could be separated on the two kinds of chiral stationary phases without derivatization and the resolution was above 2.0. The methods developed on the two kinds of chiral stationary phases are accurate, sensitive and specific.</p><p><b>CONCLUSION</b>Both the proteinate- and amylose-based chiral stationary phases can be used to separate the enantiomers of cetirizine.</p>

Determinaçäo sérica de haptoglobina, ceruloplasmina e Ó-glicoproteína ácida em cäes com gastrenterite hemorrágica / Determination of serum haptoglobin, ceruloplasmin and acid Ó-glycoprotein in dogs with haemorrhagic gastroenteritis

As proteínas de fase aguda (PFA) säo proteínas plasmáticas, cujo estímulo à síntese ocorre de forma rápida e marcante em resposta à injúria tecidual. Estas proteínas permitem o diagnóstico de processos inflamatórios em animais com supressäo ou depressäo medular. Além disso, säo úteis na monitorizaçäo da resoluçäo tecidual de traumas ou inflamaçäo e também na avaliaçäo da resposta orgânica ao tratamento. Uma vez que a leucopenia é observada nos estádios iniciais da parvovirose canina, a dosagem das PFA pode permitir a avaliaçäo do processo inflamatório sob estas condiçöes. Considerando-se estas hipóteses, foram determinados os níveis séricos das PFA (haptoglobina, ceruloplasmina e Ó-glicoproteína ácida) em 11 cäes saudáveis e 11 cäes leucopênicos com gastrenterite hemorrágica, com suspeita clínica de parvovirose canina. A avaliaçäo estatística mostrou diferença significativa, com intervalo de confiabilidade de 99 por cento (P<0,01) para a haptoglobina (p<0,0064) e para a glicoproteína ácida (p<0,0042) e 95 por cento de confiança (P<0,05) para a ceruloplasmina (p<0,0478) quando comparada com o grupo controle. Em conclusäo, cäes com gastrenterite hemorrágica durante a fase leucopênica apresentaram níveis elevados de haptoglobina, ceruloplasmina e Ó-glicoproteína ácida.