Transferrin Concentrations Research Articles

WOMEN COINFECTED WITH HIV AND VHC. PART 1. PSYCHOSOCIAL CHARACTERISTIC AND READINESS TO ANTIVIRAL THERAPY

The objective of the present study was the analysis of medical and social status of women co-infected with HIV and VHC with the following assessment of their readiness to antiviral therapy of chronic hepatitis C virus infection (CHC) taking into account the mental health and living conditions and sustaining the adherence to antiviral therapy thereafter. Materials and methods. To clarify the social and psychological status, 100 outpatient cards of women co-infected with HIV/HCV were analyzed. The in-depth study with the assessment of the psychosocial and detoxification status and the adherence to antiretroviral therapy (ART) was held in fifty patients. Results. Most of the women had a long-standing history of HIV infection and HCV. Of these, 78% underwent ART and 84,6% had a high adherence to treatment. The main social problems of the women were connected with their work (34,2%) and family circumstances (26,3%). An increase in the concentration of carbohydrate-deficient transferrin (CDT), the marker of chronic alcohol abuse, was detected in three of 50 patients, and other three of the 50 had this parameter in the zone of unstable values. 72% of the patients showed mental disorders, while more than half of them (60%) had actively used psychoactive substances, and organic symptomatic mental disorder effects were observed in 20% of the patients. Most of the women were in remission on the use of psychoactive substances. Evaluation of the depression and anxiety levels has showed scattered results but in the meantime 54% of the women expressed complaints of asthenic nature, anxious mood was marked in 38% of the patients, 40% of them earlier had been suicidally inclined. Conclusion. Taking into account the social problems in one-third of patients that may negatively affect the treatment of HCV and HIV infection, it is essential to lend complimentary psychological support and assist with solving difficulties before the treatment assignment in order to increase the adherence to treatment. Due to mental health reasons, the patients need continuous observation and periodic condition correction. The majority of surveyed agree ART of CHC at this moment and in the short term but carefully relate to offered treatment regimens and its duration. Given the mental state of the patients, it can be assumed that virus C in women with HIV/HCV co-infection should be treated with direct-acting antiviral agents that do not exacerbate existing disorders. The next issue of the journal .HIV infection and immunosuppression disorders. (2018. Vol. 10, No. 4) will present the results of the study of clinical status features and the prospects for the therapy.

Взаємозв'язок між дозою тривалого активатора рецепторів еритропоетину та оксидативним стресом у хворих, які лікуються методом гемодіалізу

Наукові дані щодо дозозалежного впливу тривалого активатора рецепторів еритропоетину (ТАРЕ) на показники оксидативного стресу та перекисного окислення ліпідів мембран еритроцитів у хворих на хронічну хворобу нирок V, які лікуються гемодіалізом (ГД), є обмеженими.
 Метою нашої роботи було оцінити взаємозв’язок між застосованою дозою ТАРЕ та інтенсивністю оксидативних процесів у ГД пацієнтів. 
 Матеріал та методи. 38 ГД пацієнтів були включені до одномоментного обсерваційного дослідження. Протокол дослідження був схвалений локальною етичною комісією ДУ «Інститут нефрології НАМН України». Усі пацієнти надали письму інформовану згоду на участь у досліджені. Пацієнти були стратифіковані за квартилями (≤ 25% та ≥ 75%) відповідно до середньої дози ТАРЕ і розподілені наступним чином: I групу склали хворі, які отримували ТАРЕ більше 6 місяців у дозі ≤ 50 мкг/міс (n = 20), до II групи увійшли хворі, у яких доза ТАРЕ склала ≥ 125 мкг/міс (n = 18). Поряд із стандартними діагностичними методами досліджували концентрацію малонового діальдегіду у сироватці (МДА) й еритроцитах (MДAe), вміст у крові церулоплазміну (ЦП) та трансферину (ТР). Крім того, визначали загальну пероксидазну активність (ЗПА) у еритроцитах, проникність еритроцитарних мембран (ПЕМ), підрахували відсоток гемолізу.
 Результати. У ГД пацієнтів, які лікувались ТАРЕ у дозі ≥ 125 мкг/міс визначено підвищення концентрації ЦР (р = 0,007) та ТР (р = 0,0003), тоді як ЗПА була статистично значуще зниженою порівняно з ІІ групою (р = 0,02). Крім того, У пацієнтів І групи встановлено вищий відсоток гемолізу (р = 0,03) та ПЕМ (р ˂ 0,0001). Використовуючи модель пробіт-регресії, ми визначили дозозалежний вплив ТАРЕ на рівень ПЕМ: χ2 = 21; р ˂ 0,0001.
 Висновки. Таким чином, застосування ТАРЕ у дозі понад 125 мкг на місяць покращує антиоксидантний статус ГД хворих, але разом з тим, підвищує гемоліз еритроцитів та ПЕМ. Отримані нами дані потребують подальшого підтвердження.

Blood serum acute phase proteins and iron dynamics during acute phase response of Salmonella enterica serotype Dublin experimentally infected buffalo calves

The study aimed to evaluate clinical signs, blood serum acute phase proteins (APP) and iron dynamics during the acute phase response (APR) of Salmonella Dublin experimentally infected Murrah buffalo calves. Six buffalo calves constituted the control group (CNT) and six were orally inoculate with 108 CFU of S. Dublin (INF). Clinical evaluation was performed, rectal swabs to detect S. Dublin strains were collected and venous blood was sampled before and throughout seven days after inoculation. The APP fractions β-haptoglobin, α-haptoglobin, ceruloplasmin and transferrin were analyzed by 1-D and 2-D electrophoresis. Proteins were identified using LC/ESI-MS/MS and NCBI database. Plasma fibrinogen, serum iron and serum haptoglobin concentrations were measured. The inoculation of 108 CFU of S. Dublin was effective in inducing clinical signs of Salmonellosis, such as hyperthermia and diarrhea. 1-DE showed that β and α-haptoglobin increased 204% (p = 0.008) and 184% (p = 0.022) 48 h after inoculation (HAI), respectively, with highest concentrations 120 HAI (498% increased, p = 0.012; 431% increased, p = 0.011) and 168 HAI (492% increased, p = 0.019; 523% increased, p = 0.028). 2-DE showed that the expression of two spots, identified as β-haptoglobin, were increased 693% (p = 0.0006) and 580% (p = 0.0003) 168 HAI, respectively, while one spot, identified as α-haptoglobin, increased 714% (p = 0.040). Haptoglobin concentrations increased 1339% (p < 0.0001) 168 HAI. 1-DE showed that ceruloplasmin increased 42% (p = 0.034) 48 HAI, with highest concentration 120 HAI (133% increased, p = 0.022). 2-DE showed that the expression of two spots, identified as ceruloplasmin, were increased 218% (p = 0.0153) and 85% (p = 0.0143) 168 HAI, respectively. Fibrinogen increased 78% (p = 0.012) 96 HAI, with highest concentration 120 HAI (increased 114%, p = 0.002). Iron decreased 33% 24 HAI (p = 0.015) and 37% 72 HAI (p = 0.029), and began to be restored 96 HAI. 1-DE showed that transferrin decreased 23% 120 HAI (p = 0.047), and that values were restored 168 HAI. 2-DE showed that expression patterns of transferrin comparing 0 h and 168 HAI were similar, evidencing that values were restored 168 HAI. In conclusion, the inoculation of 108 CFU was effective in inducing hyperthermia and diahrrea. β and α-haptoglobin, ceruloplasmin and fibrinogen worked as positive APP during the APR to S. Dublin infection and are potential biomarker candidates. Concentrations of iron and transferrin decreased during the infection, highlighting the fact that mechanisms for restricting iron availability are part of the APR triggered against S. Dublin infection in buffalo calves.

Isolation of transferrin by imprinted nanoparticles with magnetic deep eutectic solvents as monomer.

Transferrin (TrF) is a very important human body glycoprotein and a clinical biomarker which controls the body's iron ion channels and iron ion balance. Any change in TrF concentration and isoform also reflects the emergence of some diseases. In this work, we prepared magnetic molecularly imprinted nanoparticles (deep eutectic solvent-molecular imprinting polymers [DES-MIPs]) with a deep eutectic solvent (DES) as a functional monomer to separate TrF in human serum. The DES dosage for MIP, pH value, and time for adsorption have been optimized, and these materials show special adsorption properties for TrF. The maximum adsorption capacity (Qmax) and dissociation constant KL of the MIP by the Langmuir adsorption curve (R2 = 0.9949) were 37.5mg/g and 0.015g/L, respectively. The imprinting factor of the MIP is 3.50 with relative standard deviation (5.63%). In summary, the use of DES as a functional monomer in molecular imprinting technology provides a novel, efficient, and biocompatible method for the isolation and purification of proteins. Graphical abstract ᅟ.

Association of CYP3A5, CYP2C8, and ABCB1 Polymorphisms With Early Renal Injury in Chinese Liver Transplant Recipients Receiving Tacrolimus

BackgroundThe purpose of this study is to explore the association of CYP3A5, ABCB1, and CYP2C8 polymorphisms with the risk of developing early kidney impairment in Chinese liver transplant recipients receiving tacrolimus. MethodsCYP3A5, ABCB1, and CYP2C8 polymorphisms were genotyped in the Chinese liver transplant recipients in the study receiving tacrolimus for at least 2 years by polymerase chain reaction and high-resolution melting method. Serum cystatin C and urine microprotein (α1-microglobulin, microalbumin, transferrin, and immunoglobulin) of liver transplant recipients were used to determine both the status of early renal injury and the lesion part. ResultsWe documented 3 genotypes of CYP3A5 and ABCB1 and only 2 genotypes of CYP2C8 in our cohort. The levels of cystatin C and all 4 indicators of the urine microprotein in the recipient group were significantly higher than those in the control group (P < .05). The concentrations of transferrin differed significantly in each CYP3A5 genotype group (P < .05). Based on diverse CYP2C8 genotypes, we divided all the recipients into 2 groups: CYP2C8*1*1 group and CYP2C8*3*1 group. The concentrations of α1-microglobulin and cystatin C differed significantly between the 2 groups (P < .05). For CYP2C8*3, the positive predictive value is 68.5% and negative predictive value is 70.2%. For CYP3A5*3, the positive predictive value is 55.3% and negative predictive value is 60.4%. ConclusionsCYP2C8*3 and CYP3A5*3 appear to be predictive of risk of tacrolimus-induced early renal impairment. CYP3A5*3 was associated with the risk of early renal glomerular lesion, while CYP2C8*3 was associated with the risk of the tubulointerstitial injury. ABCB1 polymorphisms (both C3435T and C1236T) were not associated with the early renal injury in liver transplant recipients.

Antioxidant effects of immunomodulators in patients with recurrent pyelonephritis

The purpose of our work was to investigate the effect of immunomodulatory medicines on the intensity of oxidative stress (OS), the cytokines level and the activity of renospecific enzymes in patients with recurrent pyelonephritis (rPN).&#x0D; Methods. A prospective, randomized, open-label study involved of 100 women aged 33.4 ± 8.8 year old. According to the sensitivity of the detected pathogens all patients received antibacterial therapy for two weeks. Along with the main course of antibiotic therapy, 25 patients were assigned Sodium nucleinate at a dose of 0.25 g 4 times per day during 14 days, 18 patients were prescribed Galavit intramuscularly 2 ml per dayfor 10 days, and 27patients were prescribed Proteflazid according to the manufacturer’s instructions. The comparison group consisted of 30 women with rPN who received antibiotic therapy exclusively.Women were screened before and after the treatment. The content of malondialdehyde (MDA), ceruloplasmin (CP), transferrin (TF) and sulfhydryl groups (SH-groups) were determined in the blood by colorimetric method. Oxidative stress index (OSI) was calculated. The concentration of interleukins (IL) -1f, -4, -8, -10, -17, tumor necrosis factor a (TNF-a), transforming growth factor f (TGF-f), monocytic chemoactive protein-1 (MCP-1) and interferon y (IFN-y) were analyzed in the blood of the women using an ELISA. To evaluate the functional state of the renal parenchyma the activity of tubular lysosome enzymes a total f-N-acetylhexosaminidase and f-galactosidase were determined in urine.&#x0D; Results. The use of Sodium nucleinate decreased of the OS activity by reducing MDA level (p &lt;0.001) and increasing the concentration of CP (p &lt; 0.03). The serum levels ofIL-4 (p = 0.007), lL-17 (p = 0.04), TGF-f (p = 0.02) and MCP-1 (p = 0.03) were decrease. The use of Galavit contributed to a statistically significant decrease in the concentration of TNF-a (p &lt;0.001), IL-8(p &lt;0.001), IFN-y (p = 0.001) and TGF-f (p &lt;0.001). The administration of Proteflazid resulted in a decrease in the concentrations of IL-8 and IFN-y, with a decrease in OSI (p =0.04) compared to pre-treatment. All applied immunomodulators partially reduced the activity of renospecific enzymes markers of kidney damage.&#x0D; Conclusions. The use of immunomodulators in the complex therapy of patients with rPN contributes to the partial normalization of functional activity of immune system by the decreasing ofthe production ofcytokines as its mediators and the reducing ofthe OS intensity.

Magnetic fluorescent molecularly imprinted nanoparticles for detection and separation of transferrin in human serum

Transferrin (TrF) is an important glycoprotein and disease biomarker that controls iron ion balance in the human body. Isolation and detection of TrF have important implication for the early detection of disease. Thus, a magnetic fluorescent molecularly imprinted nanoparticles (FMINPs) was prepared for extraction and fluorescence detection of TrF. The FMINPs was prepared with two steps, the first step was the synthesis of magnetic TrF imprinted nanoparticle and the second step was introducing a near-infrared fluorescent compound (CyA) on the imprinted nanoparticles, which has a strong near infrared fluorescence emission at 730 nm while excitation at 690 nm and a large fluorescence signal quenching after adsorption of TrF. The concentration of TrF can be determined by the change of the fluorescence signal. FT-IR, TEM and fluorescence spectrophotometer were used to verify the successful preparation and the fluorescence performance of the FMINPs. Under the optimized experimental conditions, the prepared FMINPs had a great fluorescence performance, offering the lower relative standard deviation (7.7%), good analytical range (0.025–0.175 mg/mL, R2 =0.998) and lower detection limit (0.0075 mg/mL) for TrF. This method provides a new solution for the direct detection and separation of TrF in human serum samples.

Iron Status and Gestational Diabetes-A Meta-Analysis.

A meta-analysis of the association of iron overload with gestational diabetes mellitus (GDM) may inform the health debate. We performed a meta-analysis investigating the association of iron biomarkers and dietary iron exposure with GDM. We identified 33 eligible studies (N = 44,110) published in 2001–2017. The standardized mean differences (SMD) in women who had GDM compared to pregnant women without were 0.25 µg/dL (95% CI: 0.001–0.50) for iron, 1.54 ng/mL (0.56–2.53) for ferritin, 1.05% (0.02 to 2.08) for transferrin saturation, and 0.81 g/dL (0.40–1.22) for hemoglobin. Adjusted odds ratio for GDM were 1.58 (95% CI: 1.20–2.08) for ferritin, 1.30 (1.01–1.67) for hemoglobin, and 1.48 (1.29–1.69) for dietary heme intake. We did not find any differences in TIBC or transferrin concentration in women with and without GDM. We also did not find any association of increased transferrin receptor or increased intake of total dietary iron, non-heme iron or supplemental iron, with increased odds ratios for GDM. Considerable heterogeneity was present among the studies (0–99%), but no evidence of publication bias. Accumulating evidence suggests that circulating and dietary iron biomarkers among pregnant women are associated with GDM, but the results should be interpreted with caution due to the high heterogeneity of analyses. Randomized trials investigating the benefits of iron reduction in women at high risk for GDM are warranted.

Effect of Zinc Sulfate and Zinc Glycine Chelate on Concentrations of Acute Phase Proteins in Chicken Serum and Liver Tissue

The aim of the study was to determine how inorganic and organic forms of zinc affect the concentrations of C-reactive protein (CRP), serum amyloid A (SAA), alpha-1-acid glycoprotein (α-1-AGP), haptoglobin (Hp), and transferrin (TRF) in the blood and liver tissue of 450 1-day-old Ross 308 chicken. Four experimental groups received one the following: inorganic zinc (ZnSO4), a zinc phytase enzyme supplement (ZnSO4-F), organic zinc in combination with glycine (Zn-Gly), or organic zinc supplemented with phytase (Zn-Gly-F). The chicken serum and liver homogenates were assayed using an ELISA kit. The results of the study showed statistically significantly higher serum and liver concentration of SAA in the group of birds that received zinc sulfate in comparison to the group of birds receiving zinc in organic form. A statistically significantly higher serum concentration of CRP and α-1-AGP was also noted in the group receiving zinc sulfate as compared to the Zn-Gly group. Comparison of the serum concentration of TRF between the supplemented groups showed a statistically significant increase in this parameter in the Zn-Gly-F group as compared to the ZSO4-F group. The increase in the serum concentration of Hp in all groups in comparison to the control may indicate stimulation of local immune mechanisms. The results of this study showed an increase in the concentrations of APPs such as AGP and TRF following the administration of zinc glycine chelates, which may demonstrate their effect on metabolic processes in the liver and on immunocompetent cells that regulate the intensity of the immune response.

Iron status in relation to cancer risk and mortality: Findings from a population‐based prospective study

While experimental evidence suggests potential carcinogenic effects of increased iron load, there is a lack of data on iron status and cancer risk from epidemiological studies. Here, we evaluated prediagnostic serum concentrations of ferritin, iron and transferrin as well as transferrin saturation (TSAT) in relation to cancer risk and mortality in a prospective study by multivariable Cox regression analyses. A case-cohort sample of the population-based EPIC-Heidelberg Study including a random subcohort (n = 2738) and incident cases of breast cancer (n = 627), prostate cancer (n = 554), lung cancer (n = 195), colorectal cancer (n = 256) and cancer death (n = 759) was used. Ferritin levels were inversely associated with breast cancer risk in the multivariable Cox regression model, with a hazard ratio (HR) of 0.67 [95% confidence interval: 0.49, 0.92] for women in the highest quartile compared to those in the lowest quartile. Neither ferritin nor the other markers of iron status were significantly associated with colorectal, prostate or lung cancer risk. An inverse association was observed between ferritin and total cancer mortality (HR: 0.70 [0.53, 0.92]). There were no significant overall associations between serum iron, transferrin or TSAT and cancer mortality. The present findings do not support the notion of increased iron load constituting a cancer risk factor in the general population. By contrast, our analyses revealed inverse associations between ferritin levels and breast cancer risk as well as cancer mortality.

HEMATOLOGICAL AND BIOCHEMICAL EFFECTS OF PARTIAL AND COMPLETE SPLENECTOMY IN DOGS

The purpose of the current study was to describe the effect of surgical splenectomy technique either partial or complete on some biochemical and hematological parameters. Six male mature mongrel dogs were subdivided into two groups (complete and partial splenectomy), and six immature mongrel dogs were subdivided into two groups (complete and partial splenectomy). Blood samples were taken before (base line), 10, 30, and 60 days post-operative. The results showed a significant reduction in serum albumin and iron levels 10 days after partial and complete splenectomy in both immature and mature dogs. However, serum gamma globulin fraction, ferritin, transferrin, and ceruloplasmin concentrations were significantly increased at the same period following surgical operation. There was a perturbation in serum activity of transaminases, bilirubin, and urea levels. The levels of WBCs, neutrophils, lymphocytes, MCH, MCHC, and platelets in completely splenectomized immature and mature dogs were increased. While, the RBCs and Hb concentrations were significantly decreased following complete splenectomy in immature and mature dogs. These results concluded that splenectomy in dogs may induce anemia, thrombosis, and inflammatory conditions but also increase cellular and humeral immunity as a compensatory mechanism. Key words: Splenectomy, transferrin, platelets, ceruloplasmin, dogs

Clinical factors affecting salivary transferrin level, a marker of blood contamination in salivary analysis

BackgroundDiagnostic value of whole saliva may be compromised when blood contamination is present in saliva samples. Measuring transferrin level in saliva samples has been used for detecting the level of blood contamination in saliva. The aim of this study was to investigate the validity of transferrin as a proper biomarker for blood contamination in whole saliva.MethodsThirty younger (mean age: 25.9 ± 2.1 years) and twenty older (mean age: 65.1 ± 9.0 years) females were included. The index reflecting overall gingival inflammation (total gingival index), salivary flow rate, and salivary concentration and secretion rate of transferrin of each subject were analyzed.ResultsSalivary transferrin concentrations and secretion rates were higher in the younger females than in the older ones despite a lower total gingival index in the younger females. The total gingival index showed no significant correlations with the concentration or secretion rate of transferrin in either unstimulated or stimulated whole saliva of younger and older subjects. The salivary concentration of transferrin showed negative correlations with the flow rate of saliva in both the younger and older groups. There were significant positive correlations between the salivary concentrations and secretion rates of transferrin in both the younger and older groups.ConclusionsSalivary transferrin levels could be affected by other factors as well as the level of blood contamination. The influences of age, gonadal hormones, salivary flow rate, and chewing performance need to be considered when using the salivary level of transferrin as a blood contamination marker.

Preparation of cobalt phthalocyanine functionalized polymer monolith and application to enrichment of transferrin glycopeptides

Poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) (Poly(GMA-EDMA)) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid (CoPcTc) was prepared. The monolith was used for transferrin (Tf) glycopeptide enrichment. By taking advantage of hydrogen bonds between isoindole subunits of phthalocyanine and glycans and coordination interaction between cobalt and glycopeptides, the monolithic material was efficient and selective. After enrichment of transferrin through the functionalized monolith, 17 glycopeptides were identified by electrospray ionization quadrupole time-of-flight mass spectrometry. When the concentration of transferrin was reduced to 8.8×10-10mol/L, three glycopeptides could still be obtained. The present method has great potential for trace sample analysis.

Transferrin as a predictor of survival in cirrhosis.

Patients with cirrhosis frequently present with high serum ferritin and low transferrin concentrations, reflecting impaired liver function and inflammation. Recent studies have shown that transferrin and its saturation with iron are Model for End‐Stage Liver Disease–independent predictors of mortality in patients with acute‐on‐chronic liver failure or decompensated cirrhosis. The aim of this study was to evaluate the prognostic utility of serum iron parameters in relation to markers of liver function and immune activation. Clinical, demographic, and biochemical data were retrospectively analyzed from a cohort of 1255 consecutive patients with cirrhosis (age ≥ 18 years) who presented from August 1, 2004 until December 31, 2014 at the University Hospital of Innsbruck. Patients with malignancies at diagnosis including hepatocellular carcinoma were excluded. Survival analysis was carried out by Cox regression by using baseline laboratory parameters, and findings were validated in an independent patient cohort. During a median follow‐up of 2.4 years, 193 deaths occurred and 254 patients underwent liver transplantation. In patients with transferrin < 180 mg/dL, 3‐month, 1‐year, and 5‐year transplant‐free survival estimates were significantly lower (91.7%, 79.0%, and 30.5%) when compared with the group of patients with transferrin ≥ 180 mg/dL (98.9%, 95.5%, and 68.0%, P < 0.001). Transferrin predicted transplant‐free survival independently of Model for End‐Stage Liver Disease–sodium (MELD‐Na) and C‐reactive protein (CRP) in multivariate regression analysis including all patients. When patients with alcoholic or nonalcoholic fatty liver disease were excluded, transferrin was in addition an albumin‐independent predictor of transplant‐free survival. In conclusion, the association of transferrin with transplant‐free survival is independent of MELD‐Na score and CRP. In patients without fatty liver disease, transferrin also predicts survival independently of albumin. Liver Transplantation 24 343–351 2018 AASLD.

Is cord blood hepcidin influenced by the low-grade acute-phase response occurring during delivery? A small-scale longitudinal study

Aim: To measure serum hepcidin in late pregnancy and in cord blood, and to analyze relationship between hepcidin, interleukin-6, and biomarkers of fetal iron status. Materials and methods: Data from 15 uncomplicated singleton pregnancies were analyzed longitudinally in trimester 3 (T3) and at birth. Results: In T3, S-ferritin (median 14 µg/L) and transferrin (median 4.0 g/L) indicated low iron status, whereas the median soluble transferrin receptor (sTfR) was 4.0 mg/L, i.e. within the reference interval. Median T3 S-hepcidin was 7.8 ng/mL. Later on in cord blood, ferritin concentration (180 µg/L) were significantly higher, transferrin concentration (1.8 g/L) were significantly lower, and both sTfR (4.7 mg/L) and S-hepcidin concentrations (30.5 ng/mL) were significantly higher than maternal T3 concentrations. At the same time, cord blood interleukin-6 indicated an activated acute-phase reaction. In T3, after logarithmic transformation, there was a significant correlation between S-hepcidin and both S-ferritin (r = 0.691) and sTfR (r = −0.825). There was also a significant correlation between S-ferritin and both sTfR (r = −0.729) and transferrin (r = 0.549) in T3. Conclusions: Although S-ferritin, S-hepcidin, and sTfR were correlated during pregnancy, these relationships were not apparent in umbilical cord blood. Further, cord blood interleukin-6 indicated an activated acute-phase response, and sTfR, which is known to be unaffected by inflammation, indicated a low iron status in cord blood. Thus, instead of representing an enhanced iron status, the data appear to suggest that hepcidin and ferritin in cord blood may be influenced by the low-grade acute-phase response that occurs during delivery.

Tacrolimus Concentration in Saliva of Kidney Transplant Recipients: Factors Influencing the Relationship with Whole Blood Concentrations.

The objective of this study was to examine the association between tacrolimus concentration in oral fluids and in whole blood and to investigate the various factors that influence this relationship. Forty-six adult kidney transplant recipients were included in the study. Study A (ten patients) included the collection of several paired oral fluid samples by passive drool over a 12-h post-dose period. Study B (36 patients) included the collection of oral fluids pre-dose and at 2h after the tacrolimus dose under three conditions: un-stimulated, after stimulation with a tart candy, and after mouth rinsing. The tacrolimus concentration in oral fluids was measured by a specially developed sensitive and specific liquid chromatography mass spectrometry method. A salivary transferrin concentration of >1mg/dL was used as a cut-off value for oral fluid blood contamination. Rinsing the oral cavity before sampling proved to provide the most suitable sampling strategy giving a correlation coefficient value of 0.71 (p=0.001) between the tacrolimus concentration in oral fluids and the tacrolimus concentration in whole blood at trough. Mean and 95% confidence interval of tacrolimus concentration in oral fluids at the pre-dose concentration for samples collected after mouth rinsing was 584 (436, 782) pg/mL. The ratio of the tacrolimus concentration in oral fluids to the tacrolimus concentration in whole blood (*100) was 11% (95% confidence interval 9-13) for all sampling times. Oral fluid pH or weight of a saliva sample did not influence the tacrolimus concentration in oral fluids. Tacrolimus distribution into oral fluids exhibited a delay with a pronounced counter-clockwise hysteresis with respect to the time after dose. A multivariate analysis of variance revealed that the tacrolimus concentration in oral fluids is related to the tacrolimus concentration in whole blood and tacrolimus plasma-binding proteins including albumin and cholesterol. An optimal sampling strategy for the determination of the tacrolimus concentration in oral fluids was established. Measuring the tacrolimus concentration in oral fluids appears to be a feasible and non-invasive method for predicting the concentration of tacrolimus in whole blood.

Acute-phase response and its biomarkers in acute and chronic urticaria.

IntroductionSince urticaria is a persisting inflammatory disease it is important to establish the prognostic factors for the duration and severity of the disease.AimTo evaluate serum concentrations of selected acute-phase proteins (APP) in patients with various forms of urticaria as compared to healthy volunteers and also to analyze these concentrations in different types of urticaria. Additionally, to evaluate the correlation between serum levels of selected APP and disease activity.Material and methodsSerum concentrations of C-reactive protein (CRP), α1-acid glycoprotein (AGP), α1-antichymotrypsin (ACT), α1-antitrypsin (AT), ceruloplasmin (Cp), transferrin (Tf), α2-macroglobulin (α2M) and haptoglobin (Hp) were measured. Quantitative measurement was conducted using the rocket immunoelectrophoresis. Disease activity was assessed with the use of total symptom score.ResultsAnalysis of serum APP concentrations revealed statistically higher serum concentrations of CRP, AGP and ACT in the entire group of patients with urticaria in comparison with the control group. In the entire group of patients with urticaria, CRP, AGP, ACT, Cp and Hp correlated positively with disease activity, intensity of pruritus and the number and size of urticarial wheals. Statistically lower serum concentrations of CRP, ACT, Cp and Hp were detected in the group of patients with acute urticaria (AU) and angioedema together, compared to the patients suffering from AU only.ConclusionsPatients with symptoms of various forms of urticaria present a distinct profile of serum APP concentrations. A significant correlation observed between CRP, AGP, ACT, Cp, Hp and clinical activity score points to the potential role of APP as markers of the urticarial activity.

Bone turnover marker determinants in young women: results from the Safe-D study.

Background Bone turnover markers (BTMs) may provide insight into bone health in young women, but have been little studied in this demographic. We aimed to explore the association between body composition, hormonal contraception, bone mineral density and biochemical parameters and BTMs in young women. Methods Participants were community-dwelling females aged 16-25 years, living in Victoria, Australia. Carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) and total procollagen type 1 N-propeptide (P1NP) were analysed on the Roche Elecsys automated analyzer. A total of 305 were evaluated, after excluding participants with medical conditions or medications (except hormonal contraceptives), which may affect bone metabolism. Results Median (Q1, Q3) BTM values were 540 (410, 690) ng/L for CTX and 61.7 (46.2, 83.7) µg/L for P1NP. Serum CTX and P1NP were inversely associated with chronological age ( P < 0.001), transferrin ( P < 0.020) and serum dehydroepiandrosterone sulphate concentration ( P < 0.001). BTM values were up to 22% lower in combined oral contraceptive (COC) pill users ( P < 0.001). Serum CTX was inversely associated with per cent body fat ( P = 0.009) and tibial cortical volumetric bone mineral density (vBMD; P = 0.003). Serum P1NP concentrations were 23 µg/L higher in participants who reported using an osteopath in the previous year ( P = 0.007). Conclusions These data suggest that BTMs are influenced by age, COC use, body composition, iron status and hormonal profiles. Higher CTX values were associated with lower tibial cortical vBMD. Examining BTMs in relation to interventions aimed at improving bone health in young women is warranted.

Effects of Sucrosomial® iron in Pre-Clinical and Clinical Conditions of Inflammation

Introduction: Proteins such as Ferritin (Ft), Hemoglobin (Hb) and Transferrin Receptor (TfR1) are involved in tissue iron distribution while systemiciron metabolism is regulated by Hepcidin. Interleukin-6 (IL-6) release is induced in response to an inflammatory status and enhances Hepcidin expression, as consequence, dietary iron absorption and macrophage iron recycling are inhibited. Anemia of Chronic Disease (ACD) is a form of anemia associated with many different chronic disorders. It is characterized by high hepcidin and CRP or IL-6 expression and low serum iron transferrin concentration while ferritin can be normal or elevated. Oral iron delivery is especially attractive thanks to the ease of administration, but commonly used iron salts are poorly absorbed and ineffective to increase Hb concentration in particular in patients with ACD. We have developed an oral Iron formulation named Sucrosomial® Iron, preparation of ferric pyrophosphate, covered by a phospholipids plus sucrester matrix, with high bioavailability and tolerability, which promotes ferric iron absorption thanks to gastro-resistant and matrix composition properties and showed Hb concentration improvement not inferior to intravenous iron.Objective: to showpre-clinical and clinical evidences of absorption, effectiveness and tolerability of Sucrosomial Iron using in vivo and in vitro models and in patients with ACD too.Methods: To study the effects of oral supplementation on Iron metabolism and inflammatory status, Hb, Ft, TfR1, Socs3 and Hepcidin expression were analyzed. We have supplemented wild-type (wt) and iron deficient (ID) mice, maintained in iron-free diet for 8 weeks, with 1mg/kg/die of Sucrosomial® Iron or Iron Sulfate or Placebo by oral gavage, for 2 weeks. The role of Sucrosomial® Iron on the inflammatory response, was studied in LPS induced HepG2 hepatoma cells. Cells were treated with Sucrosomial® Iron and the levels of hepcidin were assessed 6, 18 and 24 hours after treatment. To show the efficacy and compliance of Sucrosomial® Iron a multi-centric randomized study on 300 patients with ACD were performed. Patients were supplemented with iron sulfate (65 mg o.i.d.), microencapsulated iron, micronized iron, Sucrosomial® Iron, heminic-chelated bisglycinated and iron chelated bisglycinated iron (30 mg t.i.d.). Median Hb value at the beginning was 8.2 g/dl. In group of patients with high CRP value median Hb value was 7.8 g/dl.Results: In mice treated with Sucrosomial® Iron, Hb level mean increase was 4,9 g/dl while TSAT value is not significantly higher than animals treated with Sulfate Iron. Furthermore mice treated with Sucrosomial® Iron showed a preferential accumulation of iron in spleen. Hepcidin and Socs3 mRNA expression was not induced during Sucrosomial® Iron treatment while was up-regulated in mice treated with Iron Sulfate (Figure 1). In vitro experiments on HepG2 LPS-induced cells displayed that treatment with Sucrosomial Iron® is able to reduce hepcidin concentration at different time points (Figure 2).Data from the clinical study showed that Sucrosomial® Iron is well tolerate and effective ACD patients. Only patients treated with Sucrosomial® Iron showed constant increase in Hb concentration over time. In all groups Hb level achieves a plateau phase after three months and ferritin level starts to increase. At three months higher levels of Hb are present in Sucrosomial® Iron (13.2 g/dl), heminic chelated bisglycinated iron (11.7 g/dl), chelated bisglycinated iron (11.3 g/dl) treated patients. In patients with high CRP level (>30 ng/ml) only those receiving Sucrosomial® Iron showed Hb increase from the tenth week and this continue up to the sixth month (Hb 12.5 g/dl) and seems to be correlated to a significantly decrease of CRP (5 mg/L) (Figure 3). Side effects are higher in ferrous sulfate (15/50) and sunactive treated groups (6/60).Conclusions: In summary, results showed that Sucrosomial® Iron treatment could regulate iron homeostasis through an increase in Hb concentration and better tolerability during inflammatory status. These evidences may suggest that this new oral iron formulation behaves differently than other oral iron salts, perhaps due to different absorption pathways. Besides we have observed a decrease in CRP and Hepcidin concentration, these results should be further investigate. [Display omitted] DisclosuresBrilli:Pharmanutra S.p.A.: Consultancy. Pera:Pharmanutra S.p.A.: Employment. Tarantino:Pharmanutra S.p.A.: Employment.

Serum ferritin and primary lung cancer.

Existing research yields conflicting results regarding the relation between iron deficiency and high serum ferritin (SF) levels in primary lung cancer patients. We investigated the concentrations of SF, hemoglobin (Hb) and transferrin (TRF) in 569 male primary lung cancer patients and 252 female primary lung cancer patients. We grouped the subjects according to gender, smoking status, menopausal status, pathological type, stage, and TNM stage. The levels of SF and TRF were correlated with T stage in male patients (p<0.01). The levels of SF and TRF were correlated with menopausal status in female patients (p<0.01). Hb was correlated with smoking status, pathological type, stage, and TNM stages in male patients(p<0.01), but in female patients, Hb was not correlated with these grouping factors(p>0.05). The levels of SF may be regulated by different mechanisms and may be of different physiological significance in different populations.