ABO blood groups and risk for obesity in Arar, Northern Saudi Arabia.

PubMed

Aboel-Fetoh, Nagah M; Alanazi, Arwa R; Alanazi, Abdullah S; Alruwili, Asma N

2016-12-01

ABO blood groups are associated with some important chronic diseases. Previous studies have observed an association between ABO blood group and risk for obesity. This study aimed to determine whether there is an association between ABO blood groups and obesity in apparently healthy attendees of primary healthcare (PHC) centers in Arar city, Northern Saudi Arabia. This cross-sectional study included 401 participants aged 15 years and older attending three randomly selected PHC centers in Arar city. Data were collected by means of personal interview using a predesigned questionnaire. Anthropometric examination included height and weight measurements with calculation of BMI. ABO and Rh blood groups were determined. The majority of the participants were female (70.8%). The mean±SD age was 28.6±9.1 years. Only 5.7% were underweight. Both normal and overweight participants were equal in number and constituted 28.4%, whereas obese individuals constituted 37.4% with a mean BMI of 28.56±8.0. Blood group O was the most common (44.1%), followed by A (30.9%), B (18.7%), and AB (6.2%). Rh-positive cases constituted 87.0%. Blood group O was the most common type among the obese individuals (44.7%), followed by A, B, and AB groups (30, 20, and 5.3%, respectively). BMI was highest (28.8±9.2) in blood group O. There were no statistically significant differences between different ABO blood groups as regards BMI, Rh, and sex. Moreover, there was no statistically significant difference between Rh type and BMI. The prevalence of obesity and overweight is high in the population attending PHC centers of Arar city, Northern Saudi Arabia. There is no association between overweight, obesity, and ABO blood groups or Rh.

Blood group A and Rh(D)-negativity are associated with symptomatic West Nile virus infection

PubMed Central

Kaidarova, Zhanna; Bravo, Marjorie D.; Kamel, Hany T.; Custer, Brian S; Busch, Michael P.; Lanteri, Marion C.

2016-01-01

Background West Nile virus (WNV) infection is mostly asymptomatic but 20% of subjects report WNV fever and 1% of patients experience neurological diseases with higher rates in elderly and immunosuppressed persons. With no treatment and no vaccine to prevent the development of symptomatic infections, it is essential to understand prognostic factors influencing symptomatic disease outcome. Host genetic background has been linked to the development of WNV neuroinvasive disease. The present study investigates the association between the ABO and Rh(D) blood group status and WNV disease outcome. Study Design and Methods The distribution of blood groups was investigated within a cohort of 374 WNV+ blood donors including 244 asymptomatic (AS) and 130 symptomatic (S) WNV+ blood donors. Logistic regression analyses were used to examine associations between A, B, O and Rh(D) blood groups and WNV clinical disease outcome. Results Symptomatic WNV+ donors exhibited increased frequencies of blood group A (S 47.6% AS 36.8%, P=0.04, OR [95%CI] 1.56 [1.01–2.40]) and Rh(D)-negative individuals (S 21.5% AS 13.1%, P=0.03, OR [95%CI] 1.82 [1.04–3.18]). Conclusion The findings suggest a genetic susceptibility placing blood group A and Rh(D)-negative individuals at risk for the development of symptomatic disease outcome after WNV infection. PMID:27189860

Rh blood phenotyping (D, E, e, C, c) microarrays using multichannel surface plasmon resonance imaging.

PubMed

Pipatpanukul, Chinnawut; Takeya, Sasaki; Baba, Akira; Amarit, Ratthasart; Somboonkaew, Armote; Sutapun, Boonsong; Kitpoka, Pimpun; Kunakorn, Mongkol; Srikhirin, Toemsak

2018-04-15

The application of Surface Plasmon Resonance Imaging (SPRi) for the detection of transmembrane antigen of the Rhesus (Rh) blood group system is demonstrated. Clinically significant Rh blood group system antigens, including D, C, E, c, and e, can be simultaneously identified via solid phase immobilization assay, which offers significant time savings and assay simplification. Red blood cells (RBCs) flowed through the micro-channel, where a suitable condition for Rh blood group detection was an RBC dilution of 1:10 with a stop-flow condition. Stop flow showed an improvement in specific binding compared to continuous flow. Rh antigens required a longer incubation time to react with the immobilized antibody than A and B antigens due to the difference in antigen type and their location on the RBC. The interaction between the immobilized antibodies and their specific antigenic counterpart on the RBC showed a significant difference in RBC removal behavior using shear flow, measured from the decay of the SPR signal. The strength of the interaction between the immobilized antibody and RBC antigen was determined from the minimum wall shear stress required to start the decay process in the SPR signal. For a given range of immobilized antibody surface densities, the Rh antigen possesses a stronger interaction than A, B, and AB antigens. Identification of 82 samples of ABO and Rh blood groups using SPRi showed good agreement with the standard micro-column agglutination technique. A wider coverage of antigenic recognition for RBC when using the solid phase immobilization assay was demonstrated for the RBC with the antigenic site located on the transmembrane protein of the clinically significant Rh antigen. Given the level of accuracy and precision, the technique showed potential for the detection of the Rh minor blood group system. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalance of ABO and Rhesus Blood Groups in Blood Donors: A Study from a Tertiary Care Teaching Hospital of Kumaon Region of Uttarakhand.

PubMed

Garg, Parul; Upadhyay, Saloni; Chufal, Sanjay Singh; Hasan, Yuman; Tayal, Ishwer

2014-12-01

Backround: ABO and Rhesus (Rh) blood group antigens are hereditary characters and are useful in population genetic studies, in resolving medico-legal issues and more importantly for the immunologic safety of blood during transfusion. This study is aimed to determine the distribution pattern of the ABO and Rh blood groups among blood donors in Kumaon region of Uttarakhand and compare it with other data from similar studies within the India and all over the world. It is a retrospective study carried out at blood bank of Shushila Tewari Hospital of Government Medical College, Haldwani from January 2012 to December 2013. The study was conducted on 12,701 blood donors. ABO and Rh typing was done using slide agglutination method with antisera ABO and Rh (Tulip diagnostics ltd). Doubtful cases were confirmed by tube agglutination method and reverse grouping using known pooled A and B cells. The age group and sex of donors, frequency of ABO and Rh blood groups were reported in simple percentages. The predominant donors belonged to age group between 18-35years (84.28%). Male donors were more than female donors, ratio being 352:1. Replacement donors (99.71%) were much more than voluntary donors (0.91%). The most common blood group was B (32.07%) and least common being AB (10.53%). Blood group 'O' and 'A' had same frequency. The prevalence of Rhesus positive and negative distribution in the studied population was 94.49% and 5.51% respectively. Blood group frequency with respect to ABO and Rhesus positive was found to be shown by formula B> O>A >AB. The frequency for ABO and Rhesus negative was given by the formula B>A>O>AB. Knowledge of frequencies of the different blood groups is very important for blood banks and transfusion service policies that could contribute significantly to the National Health System.

A brief history of human blood groups.

PubMed

Farhud, Dariush D; Zarif Yeganeh, Marjan

2013-01-01

The evolution of human blood groups, without doubt, has a history as old as man himself. There are at least three hypotheses about the emergence and mutation of human blood groups. Global distribution pattern of blood groups depends on various environmental factors, such as disease, climate, altitude, humidity etc. In this survey, the collection of main blood groups ABO and Rh, along with some minor groups, are presented. Several investigations of blood groups from Iran, particularly a large sampling on 291857 individuals from Iran, including the main blood groups ABO and Rh, as well as minor blood groups such as Duffy, Lutheran, Kell, KP, Kidd, and Xg, have been reviewed.

[Detection and analysis of anti-Rh blood group antibodies].

PubMed

Wu, Yuan-jun; Wu, Yong; Chen, Bao-chan; Liu, Yan

2008-06-01

To study the prevalence and distribution of anti-Rh blood group antibodies in Chinese population and its clinical significance. Irregular antibodies were screened and identified by Microcolum Gel Coomb's test. For those identified as positive anti-Rh samples, monoclonal antibodies (anti-D, -C, -c, -E and -e) were used to identify the specific antigen and confirm the accuracy of the irregular antibody tests. The titers, Ig-types and 37 Degrees Celsius-reactivity were tested to confirm its clinical significance. For evaluation of the origin of irregular antibodies, histories of pregnancy and transfusion were reviewed. For the newborns who had positive antibodies, their mothers were tested simultaneously to confirm the origin of the antibodies. 47 out of 54 000 (0.087%) patients were identified as positive with Rh blood group antibodies.Of them, 27 cases had history of pregnancy, 13 had transfusion and 1 had the histories of both. 6 newborns had antibodies derived form their mothers. The specificity of the antibody was as follows: 29 with anti-E (61.70%), 8 with anti-D (17.02%), anti-cE 5(10.64%), 4 with anti-c (8.51%) and 1 with anti-C (2.13%). All the 47 Rh blood group antibodies were IgG or IgG+IgM, and were reactive to red blood cells with corresponding antigens at 37 Degrees Celsius, with a highest titer of 1:4 096. The prevalence of Rh antibodies is lower in Chinese population as compared with that in White population.Of all the antibodies, anti-E is most frequently identified and anti-D was declining. Alloimmunization by pregnancy and transfusion is the major cause of Rh antibody production. Rh blood group antibodies derived from mothers are the major cause of Non-ABO-HDN.

INDIVIDUAL BLOOD DIFFERENCES IN MEXICAN INDIANS, WITH SPECIAL REFERENCE TO THE Rh BLOOD TYPES AND Hr FACTOR

PubMed Central

Wiener, Alexander S.; Zepeda, J. Preciado; Sonn, Eve B.; Polivka, H. R.

1945-01-01

98 Mexican Indians were tested for the blood properties A-B-O, A1-A2, M-N, P, Rh'-Rh''-Rh0-rh, and Hr. Of the 98 Indians, 90.8 per cent belonged to group 0, 6.1 per cent belonged to A1, and 3.1 per cent to group B. There were 61.2 per cent of type M, 3.1 per cent of type N, and 35.7 per cent of type MN. Of the 95 Mexican Indians tested with anti-P serum, 21.1 per cent were found to lack the P agglutinogen. In tests for the Rh blood types, 48.0 per cent of the Indians were found to belong to type Rh1, 9.2 per cent to type Rh2, 41.8 per cent to type Rh1Rh2, and 1 per cent to type Rh0. There were no bloods giving intermediate reactions. Of the 95 Indians tested for the Hr factor 44.2 per cent were found to lack this property. The reactions for the Rh blood types and Hr factor were correlated with each other and the results supported the conclusion of Race et al. that in addition to the six standard allelic genes and the so called intermediate genes, there is one or possibly two genes having the property of determining agglutinogens which react with anti-Rh' and anti-Rh'' sera, but not with anti-Hr serum. This gene (or genes) appears to be relatively common among Mexican Indians (approximately 3.3 per cent) in contrast to its rareness in white individuals. PMID:19871476

Qualitative Analysis of Primary Fingerprint Pattern in Different Blood Group and Gender in Nepalese

PubMed Central

Maharjan, Niroj; Adhikari, Nischita; Shrestha, Pragya

2018-01-01

Dermatoglyphics, the study of epidermal ridges on palm, sole, and digits, is considered as most effective and reliable evidence of identification. The fingerprints were studied in 300 Nepalese of known blood groups of different ages and classified into primary patterns and then analyzed statistically. In both sexes, incidence of loops was highest in ABO blood group and Rh +ve blood types, followed by whorls and arches, while the incidence of whorls was highest followed by loops and arches in Rh −ve blood types. Loops were higher in all blood groups except “A –ve” and “B –ve” where whorls were predominant. The fingerprint pattern in Rh blood types of blood group “A” was statistically significant while in others it was insignificant. In middle and little finger, loops were higher whereas in ring finger whorls were higher in all blood groups. Whorls were higher in thumb and index finger except in blood group “O” where loops were predominant. This study concludes that distribution of primary pattern of fingerprint is not related to gender and blood group but is related to individual digits. PMID:29593909

[Frequencies of blood groups, ABO and Rh D incompatibility in post-delivery women and their liveborn].

PubMed

Baiochi, Eduardo; Camano, Luiz; Sass, Nelson; Colas, Osmar Ribeiro

2007-01-01

This study aimed to assess the frequency of different blood phenotypes and to predict the risk of Rh D alloimmunization and maternal-fetal incompatibility in a Brazilian population living in the West zone of the city of São Paulo-Brazil. This descriptive study evaluated 2,372 post-delivery women and their liveborn during one year. Blood types were analyzed by means of tube agglutination tests. The blood type frequencies were: 50.67 O, 32.17 A, 13.45 B, 3.75 AB, 90.34 Rh D(+) and 9.66 Rh D(-). ABO maternal-fetal incompatibility was detected in 18.4% and Rh D incompatibility in 7%. The fraction of Rh D(-) population at high risk for Rh D alloimmunization was 82%, emphasizing the importance of Rh D alloimmunization profilaxis.

Recombinant human interleukin-3 (rhIL-3) enhances the mobilization of peripheral blood progenitor cells by recombinant human granulocyte colony-stimulating factor (rhG-CSF) in normal volunteers.

PubMed

Huhn, R D; Yurkow, E J; Tushinski, R; Clarke, L; Sturgill, M G; Hoffman, R; Sheay, W; Cody, R; Philipp, C; Resta, D; George, M

1996-06-01

To identify a precisely timed and safe protocol for progenitor cell mobilization, we studied the effects of rhIL-3 and rhG-CSF administration to normal volunteers. rhG-CSF 5 micrograms/kg/d was administered subcutaneously (s.c.) for 7 consecutive days either alone or preceded by rhIL-3 5 micrograms/kg/d s.c. for 4 consecutive days in sequential or partially overlapping schedules. The combined cytokines were well-tolerated--adverse effects were similar to those of the individual agents. Total white blood cell (WBC) and neutrophil counts rose briskly in response to rhG-CSF, and peak mean values were similar between treatment cohorts. Mean platelet counts were modestly elevated during rhG-CSF treatment only in the cohorts receiving rhIL-3 and rhG-CSF. Mean circulating CD34+ cells peaked on day 5 in the rhG-CSF group (38.9+/-14.3/microliter), day 6 in the sequential rhIL-3/rhG-CSF group (56.4+/-12.4/microliter), and day 6 in the partial overlap group (46.1+/-10.9/microliter). On day 3, mean CD34+ cell counts of the subjects who received sequential treatment were markedly higher than observed in the other groups (p<0.05) and were estimated to have been sufficient for collection of adequate grafts by single 10-L leukapheresis procedures in 60% of subjects. Circulating clonogenic cells (CFU-GM and/or BFU-E) were substantially higher in the sequential group than the rhG-CSF group on days 3-6 but were only minimally elevated above baseline in the partial overlap group. The numbers of circulating CD34+/Lin-/Thy-1+ cells (putative stem cells) were increased substantially, especially in the sequential group. On the basis of this pilot trial, we conclude that priming with rhIL-3 is a safe and well-tolerated method for enhancing the mobilization of human blood progenitors and stem cells by rhG-CSF.

Toxoplasmosis-associated difference in intelligence and personality in men depends on their Rhesus blood group but not ABO blood group.

PubMed

Flegr, Jaroslav; Preiss, Marek; Klose, Jiří

2013-01-01

The parasite Toxoplasma gondii influences the behaviour of infected animals and probably also personality of infected humans. Subjects with a Rhesus-positive blood group are protected against certain behavioural effects associated with Toxoplasma infection, including the deterioration of reaction times and personality factor shift. Here, we searched for differences in the toxoplasmosis-associated effects between RhD-positive and RhD-negative subjects by testing 502 soldiers with two personality tests and two intelligence tests. The infected subjects expressed lower levels of all potentially pathognomic factors measured with the N-70 questionnaire and in neurasthenia measured with NEO-PI-R. The RhD-positive, Toxoplasma-infected subjects expressed lower while RhD-negative, Toxoplasma-infected subjects expressed higher intelligence than their Toxoplasma-free peers. The observed Toxoplasma-associated differences were always larger in RhD-negative than in RhD-positive subjects. RhD phenotype plays an important role in the strength and direction of association between latent toxoplasmosis and not only psychomotor performance, but also personality and intelligence.

Toxoplasmosis-Associated Difference in Intelligence and Personality in Men Depends on Their Rhesus Blood Group but Not ABO Blood Group

PubMed Central

Flegr, Jaroslav; Preiss, Marek; Klose, Jiří

2013-01-01

Background The parasite Toxoplasma gondii influences the behaviour of infected animals and probably also personality of infected humans. Subjects with a Rhesus-positive blood group are protected against certain behavioural effects associated with Toxoplasma infection, including the deterioration of reaction times and personality factor shift. Methodology/Principal Findings Here, we searched for differences in the toxoplasmosis-associated effects between RhD-positive and RhD-negative subjects by testing 502 soldiers with two personality tests and two intelligence tests. The infected subjects expressed lower levels of all potentially pathognomic factors measured with the N-70 questionnaire and in neurasthenia measured with NEO-PI-R. The RhD-positive, Toxoplasma-infected subjects expressed lower while RhD-negative, Toxoplasma-infected subjects expressed higher intelligence than their Toxoplasma-free peers. The observed Toxoplasma-associated differences were always larger in RhD-negative than in RhD-positive subjects. Conclusions RhD phenotype plays an important role in the strength and direction of association between latent toxoplasmosis and not only psychomotor performance, but also personality and intelligence. PMID:23593448

[Observation on gene polymorphism of Rh blood group in Chinese Han nationality].

PubMed

Lan, Jiong-Cai; Wang, Cong-Rong; Wei, Ya-Ming; Zhou, Hua-You; Cao, Qiong; Zhang, Yin-Ze; Jiang, KuReXi; Wu, Da-Lin; Liu, Zhong

2003-12-01

To observe the gene polymorphism of Rh blood group in unrelated random individuals and families for Chinese Han nationality, polymerase chain reaction-sequence specific primer (PCR-SSP) was used to amplify the Rh C/E gene, RhD gene, exons, intron 2 and 10, insert and Rh Box in 160 blood samples of RhD positive unrelated individuals and 71 samples of RhD negative unrelated individuals and 7 samples of families whose probands were RhD-negative. The results showed that RhD genes of RhD-negative individuals with C antigens were polymorphism, three forms were found for D exon including intact, partial deletion and complete deletion exons. Insert fragments and Rh Box were found in most cases of families whose probands were RhD-negative and its inheritance accorded with the Mendel's Law, and it did not affect the expression of RhD gene. "Normal" RhD exon 4 amplifying product was not found in all of the samples. It was concluded that gene structure of the RhD-negative in Chinese was polymorphism, intact, partial deletion and complete deletion exons were found in the individuals with C antigen and probably existed specific D (nf) Ce haplotype. The function of insert was uncertain. The Rh gene sequences of Chinese Han nationality are different from those of Caucasian and the Rh gene library based on Han nationality should be established.

Toxoplasma and reaction time: role of toxoplasmosis in the origin, preservation and geographical distribution of Rh blood group polymorphism.

PubMed

Novotná, M; Havlícek, J; Smith, A P; Kolbeková, P; Skallová, A; Klose, J; Gasová, Z; Písacka, M; Sechovská, M; Flegr, J

2008-09-01

The RhD protein which is the RHD gene product and a major component of the Rh blood group system carries the strongest blood group immunogen, the D-antigen. This antigen is absent in a significant minority of the human population (RhD-negatives) due to RHD deletion or alternation. The origin and persistence of this RhD polymorphism is an old evolutionary enigma. Before the advent of modern medicine, the carriers of the rarer allele (e.g. RhD-negative women in the population of RhD-positives or RhD-positive men in the population of RhD-negatives) were at a disadvantage as some of their children (RhD-positive children born to pre-immunized RhD-negative mothers) were at a higher risk of foetal or newborn death or health impairment from haemolytic disease. Therefore, the RhD-polymorphism should be unstable, unless the disadvantage of carriers of the locally less abundant allele is counterbalanced by, for example, higher viability of the heterozygotes. Here we demonstrated for the first time that among Toxoplasma-free subjects the RhD-negative men had faster reaction times than Rh-positive subjects and showed that heterozygous men with both the RhD plus and RhD minus alleles were protected against prolongation of reaction times caused by infection with the common protozoan parasite Toxoplasma gondii. Our results suggest that the balancing selection favouring heterozygotes could explain the origin and stability of the RhD polymorphism. Moreover, an unequal prevalence of toxoplasmosis in different countries could explain pronounced differences in frequencies of RhD-negative phenotype in geographically distinct populations.

Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR-2721, rhIL-11 and rhG-CSF on radiation-injured mice

PubMed Central

Jiang, Shuqi; Shen, Xianrong; Liu, Yuming; He, Ying; Jiang, Dingwen; Chen, Wei

2015-01-01

This study investigated the radioprotective effect of Sipunculus nudus L. polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided into seven groups: the control group, the model group and five administration groups. All groups, except the control group, were exposed to a 5 Gy 60Co γ-ray beam. Blood parameters [including white blood cell (WBC), red blood cell (RBC) and platelet counts and hemoglobin level] were assessed three days before irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen, thymus and testicular indices, DNA contents of bone marrow cells, bone marrow nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and estradiol levels in the serum were assessed on the 14th day after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and platelet counts and hemoglobin levels in irradiated mice, and synergistic promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and sperm counts in irradiated mice. The synergistic administration increased the serum SOD activities and serum testosterone content of irradiated mice, but synergy decreased the content of serum MDA and estradiol in irradiated mice. These results suggest that the combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF should increase the efficacy of these drugs for acute radiation sickness, protect immunity, hematopoiesis and the reproductive organs of irradiated-damaged mice, and improve oxidation resistance in the body. PMID:25852150

Association between ABO and Rh Blood Groups and Risk of Preeclampsia: A Case-Control Study from Iran.

PubMed

Aghasadeghi, Firoozeh; Saadat, Mostafa

2017-04-15

Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality. There is a genetic component in the development of PE with estimated heritability around 0.47. Several studies have investigated the association between maternal ABO blood groups (OMIM 110300) and risk of PE, with contradictory results have emerged. Considering that there is no study in this filed from Iranian population, the present case-control study was carried out at Shiraz (south-west Iran). In this study 331 women; 121 pregnant with PE and 210 normotensive pregnant women were included. Using blood group O (for ABO blood groups) or Rh+ (for Rh blood groups) as a reference, odds ratios (ORs) and its 95% confidence intervals (95% CI) of PE risk were estimated from logistic regression analysis. Although the A (OR = 0.67, 95% CI = 0.39-1.17, P = 0.165), B (OR = 0.86, 95% CI = 0.48-1.53, P = 0.615) and AB (OR = 1.14, 95% CI = 0.37-3.45, P = 0.812) phenotypes showed lower risks compared with the O blood group, statistical analysis indicated that there was no significant association between ABO phenotypes and risk of PE. The frequency of Rh- phenotype was higher among PE patients compared with the control group. However, the association was not significant (OR = 1.79, 95% CI = 0.69-4.65, P = 0.229). Adjusted ORs for age of participants and parity did not change the above-mentioned associations. Our present findings indicate that there is no association between ABO and Rh blood groups and risk of PE in Iranian population.

A novel paper-based assay for the simultaneous determination of Rh typing and forward and reverse ABO blood groups.

PubMed

Noiphung, Julaluk; Talalak, Kwanrutai; Hongwarittorrn, Irin; Pupinyo, Naricha; Thirabowonkitphithan, Pannawich; Laiwattanapaisal, Wanida

2015-05-15

We propose a new, paper-based analytical device (PAD) for blood typing that allows for the simultaneous determination of ABO and Rh blood groups on the same device. The device was successfully fabricated by using a combination of wax printing and wax dipping methods. A 1:2 blood dilution was used for forward grouping, whereas whole blood could be used for reverse grouping. A 30% cell suspension of A-cells or B-cells was used for haemagglutination on the reverse grouping side. The total assay time was 10 min. The ratio between the distance of red blood cell movement and plasma separation is the criterion for agglutination and indicates the presence of the corresponding antigen or antibody. The proposed PAD has excellent reproducibility in that the same blood groups, namely A, AB, and O, were reported by using different PADs that were fabricated on the same day (n=10). The accuracy for detecting blood group A (n=12), B (n=13), AB (n=9), O (n=14), and Rh (n=48) typing were 92%, 85%, 89%, 93%, and 96%, respectively, in comparison with the conventional slide test method. The haematocrit of the sample affects the accuracy of the results, and appropriate dilution is suggested before typing. In conclusion, this study proposes a novel method that is straightforward, time-saving, and inexpensive for the simultaneous determination of ABO and Rh blood groups, which is promising for use in developing countries. Copyright © 2015 Elsevier B.V. All rights reserved.

Association of ABO and Rh blood groups with type 2 diabetes mellitus.

PubMed

Meo, S A; Rouq, F A; Suraya, F; Zaidi, S Z

2016-01-01

The phenotypic "ABO" blood groups are inherited antigenic substances which are found on the surface of red blood cells in addition to other tissues. Certain hypothesis advocates that genetic predisposition like "ABO" blood group would be associated with occurrence of diseases including type 2 diabetes. This study aimed to investigate the potential association between "ABO" and "Rhesus" blood groups with type 2 diabetes. We identified 47 research documents in a data based search including ISI-Web of Science, EMBASE and PubMed. Literature was explored using the key terms including "ABO blood groups" "type 2 diabetes". Studies in which "ABO" blood types and diabetes mellitus were discussed included without restrictions of research documents, types, status and language of the publications. Finally, 15 publications which matched our criteria were included, and remaining studies were excluded. Blood group "B" was associated with high incidence of type 2 diabetes and blood group "O" has a minimum association with type 2 diabetes. Blood group "A" and "AB" were almost equally distributed in both diabetic and non-diabetic population. However, we were unable to find an association between "Rh+ve" and "Rh-ve" blood groups with type 2 diabetes. Subjects with blood group "B" are at high risk while individuals with blood group "O" are at low peril of evolving type 2 diabetes. It is suggested that subjects with blood group "B" should be closely monitored by physicians as these subjects have an increased risk of type 2 diabetes.

Structural analysis of the RH-like blood group gene products in nonhuman primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salvignol, I.; Calvas, P.; Blancher, A.

1995-03-01

Rh-related transcripts present in bone marrow samples from several species of nonhuman primates (chimpanzee, gorilla, gibbon, crab-eating macaque) have been amplified by RT-polymerase chain reaction using primers deduced from the sequence of human RH genes. Nucleotide sequence analysis of the nonhuman transcripts revealed a high degree of similarity to human blood group Rh sequences, suggesting a great conservation of the RH genes throughout evolution. Full-length transcripts, potentially encoding 417 amino acid long proteins homologous to Rh polypeptides, were characterized, as well as mRNA isoforms which harbored nucleotide deletions or insertions and potentially encode truncated proteins. Proteins of 30-40,000 M{sub r},more » immunologically related to human Rh proteins, were detected by western blot analysis with antipeptide antibodies, indicating that Rh-like transcripts are translated into membrane proteins. Comparison of human and nonhuman protein sequences was pivotal in clarifying the molecular basis of the blood group C/c polymorphism, showing that only the Pro103Ser substitution was correlated with C/c polymorphism. In addition, it was shown that a proline residue at position 102 was critical in the expression of C and c epitopes, most likely by providing an appropriate conformation of Rh polypeptides. From these data a phylogenetic reconstruction of the RH locus evolution has been calculated from which an unrooted phylogenetic tree could be proposed, indicating that African ape Rh-like genes would be closer to the human RhD gene than to the human RhCE gene. 55 refs., 4 figs., 1 tab.« less

Significance of ABO-Rh blood groups in response and prognosis in breast cancer patients treated with radiotherapy and chemotherapy.

PubMed

Cihan, Yasemin Benderli

2014-01-01

To evaluate whether ABO-Rh blood groups have significance in the treatment response and prognosis in patients with non-metastatic breast cancer. We retrospectively evaluated files of 335 patients with breast cancer who were treated between 2005 and 2010. Demographic data, clinic- pathological findings, treatments employed, treatment response, and overall and disease-free survivals were reviewed. Relationships between clinic-pathological findings and blood groups were evaluated. 329 women and 6 men were included to the study. Mean age at diagnosis was 55.2 years (range: 26-86). Of the cases, 95% received chemotherapy while 70% were given radiotherapy and 60.9% adjuvant hormone therapy after surgery. Some 63.0% were A blood group, 17.6% O, 14.3% B and 5.1% AB. In addition, 82.0% of the cases were Rh-positive. Mean follow-up was 24.5 months. Median overall and progression-free survival times were 83.9 and 79.5 months, respectively. Overall and disease-free survival times were found to be higher in patients with A and O blood groups (p<0.05). However rates did not differ with the Rh-positive group (p=0.226). In univariate and multivariate analyses, ABO blood groups were identified as factors that had significant effects on overall and disease-survival times (p=0.011 and p=0.002). It was seen that overall and disease-free survival times were higher in breast cancer patients with A and O blood groups when compared to those with other blood groups. It was seen that A and O blood groups had good prognostic value in patients with breast cancer.

Fingerprints as an Alternative Method to Determine ABO and Rh Blood Groups.

PubMed

Chaudhary, Sonam; Deuja, Sajana; Alam, Munna; Karmacharya, Poonam; Mondal, Monami

2017-01-01

Blood grouping is conventionally done with invasive method by taking blood samples. The objective of this study is to determine blood group with uninvasive procedure by taking fingerprints of the participants and know the associations between their fingerprints and blood groups. Seven hundred participants of both genders with no any age limitation from Manipal Teaching Hospital and Manipal College of Medical Sciences were randomly selected. The blood grouping was done by cross reacting blood sample with the antibodies. The fingerprints were taken with the help of stamp pad imprinting the finger ridges over A4 size white papers. The loop, whorl and arch patterns were studied. O+ve blood group 224 (32%) was most prevalent among 700 participants. The loop pattern was highly distributed 3708 (53%) in all blood groups except in A-ve blood group with highest distribution of whorl 20 (40%). The mean comparisons of specific fingerprint in total and also in individual fingers with different ABO and ABO-Rh blood groups showed no any statistical association with P>0.05. However, the loop distribution in individual finger was highest in right middle finger (M) of B-ve blood group 5 (10%). The whorl distribution in individual finger was highest in right index (I), left thumb (T) and left ring (R) fingers of AB+ve blood group 20 (5.5% each). Similarly, the arch distribution was highest in right index fingers of A-ve blood group 3 (6%). The mean comparison of different fingerprints with ABO and Rh blood groups showed no significant statistical association concluding fingerprints cannot be used for blood grouping.

Frequency of ABO/Rhesus Blood Groups in Patients with Diabetes Mellitus.

PubMed

Oner, Can; Dogan, Burcu; Telatar, Berrin; Celik Yagan, Canan Fidan; Oguz, Aytekin

2016-01-01

The correlation between ABO/Rh blood groups and diabetes mellitus is still controversial. The aim of this study was to determine the relationship between ABO/Rhesus blood groups and diabetes in Turkish population. This cross-sectional study was conducted in Istanbul Medeniyet University Göztepe Education and Training Hospital's Diabetes Units. The study group was composed of 421 patients with type-1 diabetes, 484 patients with type-2 diabetes and 432 controls. Blood samples were collected and tested for ABO/Rhesus blood groups. Data was analyzed by SPSS version 17.0. A significant association was found between blood groups and diabetes mellitus. The frequency of AB blood group was significantly higher in type-1 diabetics; and A blood group was significantly higher in type-2 diabetics. Furthermore, Rh negativity were significantly more frequent in type-2 diabetics.

Association of ABO blood groups and Rh factor with retinal and choroidal thickness.

PubMed

Teberik, Kuddusi; Eski, Mehmet Tahir

2018-06-01

To evaluate if ABO blood group and Rh factor have an effect on retinal and choroidal thickness. This study was designed prospectively. Retinal nerve fiber layer, retinal, and choroidal thicknesses were measured with spectral-domain optical coherence tomography. Retinal and choroidal thickness measurements (one subfoveal, three temporal, and three nasal) were obtained at 500-μm intervals up to 1500 μm with the caliper system. In this study, 109 male and 151 female, 260 individuals in total were included. There were 125 subjects in group A, 29 in group B, 34 in group AB, and 72 in group O. Rh factor was positive in 194 subjects and negative in 66. There was no significant difference between the groups regarding age (p = 0.667). The groups did not show any statistical difference in retinal nerve fiber layer thickness. There was significant difference found for mean retinal thickness at temporal 1000 μm when four groups were compared (p = 0.037). No statistically significant difference was detected for the remaining retinal and choroidal sectoral regions. The groups did not statistically significantly differ concerning Rh factor (p > 0.05). Although we found a significant difference in retinal thickness in the temporal retina between group B with group A and group O, we suggest that both blood group and Rh factor have no effect on retinal and choroidal thickness.

Short-term application of low-dose growth hormone in surgical patients: Effects on nitrogen balance and blood glucose

PubMed Central

Zhang, Ming-Ming; Wu, Xiao-Ting; Zhou, Yong; Qian, Kun; Zheng, Ya-Min

2007-01-01

AIM: To investigate the effectiveness and safety of recombinant human growth hormone (rhGH) in postoperative patients. METHODS: A total of 48 consecutive patients undergoing abdominal operations were randomized to receive either subcutaneous rhGH (0.15 IU/kg) or placebo (menstruum) injections daily for 7 d after surgery. The two groups had similar nutritional intake. Blood samples for serum fibronectin, albumin, prealbumin, transferrin and the total lymphocyte count, as well as glucose levels were collected to study the rhGH effect. Basal laboratory evaluation, and nutritional status were estimated on d 1 before as baseline and d 3 and 10 after operation using standard laboratory techniques. Nitrogen balance was measured from d 3 to 9 after operation. RESULTS: The cumulative nitrogen balance was significantly improved in rhGH group compared with the placebo group (11.37 ± 16.82 vs -9.11 ± 17.52, P = 0.0003). Serum fibronectin was also significantly higher in the rhGH group than in the placebo group (104.77 ± 19.94 vs 93.03 ± 16.03, P < 0.05), whereas changes in serum albumin, prealbumin, transferrin and total lymphocyte counts were not statistically significant. Mean blood glucose levels were significantly higher in the rhGH group from d 3 to 6 after operation. CONCLUSION: If blood glucose can be controlled, low-dose growth hormone together with hypocaloric nutrition is effective on improving positive nitrogen balance and protein conservation and safe is in postoperative patients. PMID:17230618

Effect of a single injection of gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) on testicular blood flow measured by color doppler ultrasonography in male Shiba goats

PubMed Central

SAMIR, Haney; SASAKI, Kazuaki; AHMED, Eman; KAREN, Aly; NAGAOKA, Kentaro; EL SAYED, Mohamed; TAYA, Kazuyoshi; WATANABE, Gen

2015-01-01

Although color Doppler ultrasonography has been used to evaluate testicular blood flow in many species, very little has been done in goat. Eight male Shiba goats were exposed to a single intramuscular injection of either gonadotropin-releasing hormone (GnRH group; 1 µg/kg BW) or human chorionic gonadotropin (hCG group; 25 IU/kg BW). Plasma testosterone (T), estradiol (E2) and inhibin (INH) were measured just before (0 hr) and at different intervals post injection by radioimmunoassay. Testis volume (TV) and Doppler indices, such as resistive index (RI) and pulsatility index (PI) of the supratesticular artery, were measured by B-mode and color Doppler ultrasonography, respectively. The results indicated an increase in testicular blood flow in both groups, as RI and PI decreased significantly (P<0.05), but this increase was significant higher and earlier in hCG group (1 hr) than in the GnRH group (2 hr). A high correlation was found for RI and PI with both T (RI, r= −0.862; PI, r= −0.707) and INH in the GnRH group (RI, r=0.661; PI, r=0.701). However, a significant (P<0.05) correlation was found between E2 and both RI (r= −0.610) and PI (r= −0.763) in hCG group. In addition, TV significantly increased and was highly correlated with RI in both groups (GnRH, r= −0.718; hCG, r= −0.779). In conclusion, hCG and GnRH may improve testicular blood flow and TV in Shiba goats. PMID:25715956

Phenotypic Profile of Rh and Kell Blood Group Systems among Blood Donors in Cote d'Ivoire, West Africa

PubMed Central

Siransy Bogui, L.; Dembele, B.; Sekongo, Y.; Abisse, S.; Konaté, S.; Sombo, M.

2014-01-01

Few countries in sub-Saharan Africa make systematic searches for antigens C, c, E, and e of the Rh and Kell system antigens in the donor and recipient, thereby exposing transfused patients. Purpose and Objectives. In this paper, we propose to determine the red cell Rh and Kell blood groups among blood donors from traditional techniques to improve medical care of transfused patients. This study will allow us to assess the frequency of blood group antigens in these systems. Study Design and Methods. We carried out a study on the red cell typing in the blood donor population of the National Blood Transfusion Center in Abidjan. This study was performed on 651 blood donors. Results. For the Rh system, the antigen frequencies of D, c, e, C, and E are, respectively, 92.93%, 99.85%, 99.85%, 21.97%, and 13.82%. K antigen is found in 0.77% of donors. Discussion and Conclusion. Although the frequencies of the most immunogenic antigens are lower than in the white race, lack of preventive measures makes the immunological risk high in Africa. Furthermore, Africa is full of specificities that are important to note for a better care of our patients. PMID:25328758

Accuracy of user-friendly blood typing kits tested under simulated military field conditions.

PubMed

Bienek, Diane R; Charlton, David G

2011-04-01

Rapid user-friendly ABO-Rh blood typing kits (Eldon Home Kit 2511, ABO-Rh Combination Blood Typing Experiment Kit) were evaluated to determine their accuracy when used under simulated military field conditions and after long-term storage at various temperatures and humidities. Rates of positive tests between control groups, experimental groups, and industry standards were measured and analyzed using the Fisher's exact chi-square method to identify significant differences (p < or = 0.05). When Eldon Home Kits 2511 were used in various operational conditions, the results were comparable to those obtained with the control group and with the industry standard. The performance of the ABO-Rh Combination Blood Typing Experiment Kit was adversely affected by prolonged storage in temperatures above 37 degrees C. The diagnostic performance of commercial blood typing kits varies according to product and environmental storage conditions.

ABO/Rh Blood Groups and Risk of HIV Infection and Hepatitis B Among Blood Donors of Abidjan, Côte D'ivoire.

PubMed

Siransy, Liliane Kouabla; Nanga, Zizendorf Yves; Zaba, Flore Sandrine; Tufa, Nyasenu Yawo; Dasse, Sery Romuald

2015-09-01

Hepatitis B and HIV infection are two viral infections that represent real global public health problems. In order to improve their management, some hypotheses suggest that genetic predispositions like ABO and Rh blood groups would influence the occurrence of these diseases. The aim of the present study was to examine the association between ABO and Rhesus blood groups and the susceptibility to HIV infection and hepatitis B. We conducted a cross-sectional and analytical study in a population of voluntary blood donors in the Blood Transfusion Center of Abidjan. All blood donors who donated blood between January and June 2014 were tested for HBs antigen and anti-HIV antibodies (ELISA tests) and were ABO typed. The total number of examined blood donors during this period was 45,538, of which 0.32% and 8.07% were respectively infected with HIV and hepatitis B virus. O-group donors were more infected than non-O donors. Our study is an outline concerning the search for a link between ABO and Rh blood groups and hepatitis B and HIV infection. Further studies should be conducted to confirm the interaction between these two infections and contribute to the search for new therapeutic approaches.

Administration of gonadotropin-releasing hormone agonist on Day 5 increases luteal blood flow and improves pregnancy prediction accuracy on Day 14 in recipient Holstein cows

PubMed Central

KANAZAWA, Tomomi; SEKI, Motohide; ISHIYAMA, Keiki; ARASEKI, Masao; IZAIKE, Yoshiaki; TAKAHASHI, Toru

2017-01-01

This study assessed the effects of gonadotropin-releasing hormone (GnRH) treatment on Day 5 (Day 0 = estrus) on luteal blood flow and accuracy of pregnancy prediction in recipient cows. On Day 5, 120 lactating Holstein cows were randomly assigned to a control group (n = 63) or GnRH group treated with 100 μg of GnRH agonist (n = 57). On Days 3, 5, 7, and 14, each cow underwent ultrasound examination to measure the blood flow area (BFA) and time-averaged maximum velocity (TAMV) at the spiral arteries at the base of the corpus luteum using color Doppler ultrasonography. Cows with a corpus luteum diameter ≥ 20 mm (n = 120) received embryo transfers on Day 7. The BFA values in the GnRH group were significantly higher than those in the control group on Days 7 and 14. TAMV did not differ between these groups. According to receiver operating characteristic analyses to predict pregnancy, a BFA cutoff of 0.52 cm2 yielded the highest sensitivity (83.3%) and specificity (90.5%) on Day 7, and BFA and TAMV values of 0.94 cm2 and 44.93 cm/s, respectively, yielded the highest sensitivity (97.1%) and specificity (100%) on Day 14 in the GnRH group. The areas under the curve for the paired BFA and TAMV in the GnRH group were 0.058 higher than those in the control group (0.996 and 0.938, respectively; P < 0.05). In conclusion, GnRH treatment on Day 5 increased the luteal BFA in recipient cows on Days 7 and 14, and improved the accuracy of pregnancy prediction on Day 14. PMID:28552886

An effective diagnostic strategy for accurate detection of RhD variants including Asian DEL type in apparently RhD-negative blood donors in Korea.

PubMed

Seo, M H; Won, E J; Hong, Y J; Chun, S; Kwon, J R; Choi, Y S; Kim, J N; Lee, S A; Lim, A H; Kim, S H; Park, K U; Cho, D

2016-11-01

The purpose of this study was to provide an effective RHD genotyping strategy for the East Asian blood donors. RhD phenotyping, weak D testing and RhCE phenotyping were performed on 110 samples from members of the RhD-negative club, private organization composed of RhD-negative blood donors, in the GwangJu-Chonnam region of Korea. The RHD promoter, intron 4, and exons 7 and 10 were analysed by real-time PCR. Two nucleotide changes (c.1227 G>A, and c.1222 T>C) in exon 9 were analysed by sequencing. Of 110 RhD-negative club members, 79 (71·8%) showed complete deletion of the RHD gene, 10 (9·1%) showed results consistent with RHD-CE-D hybrid, and 21 (19·1%) showed amplification of RHD promoter, intron 4, and exons 7 and 10. Of the latter group, 16 (14·5%) were in the DEL blood group including c.1227 G>A (N = 14) and c.1222 T>C (N = 2), 2 (1·8%) were weak D, 1(0·9%) was partial D, and 2 (1·8%) were undetermined. The RhD-negative phenotype samples consisted of 58 C-E-c+e+, 19 C-E+c+e+, 3 C-E+c+e-, 21 C+E-c+e-, 6 C+E-c+e+ and 3 C+E-c-e + . Notably, all 58 samples with the C-E-c+e+ phenotype were revealed to have complete deletion of the RHD gene. The C-E-c+e+ phenotype showed 100% positive predictive value for detecting D-negative cases. RHD genotyping is not required in half of D-negative cases. We suggest here an effective RHD genotyping strategy for accurate detection of RhD variants in apparently RhD-negative blood donors in East Asia. © 2016 International Society of Blood Transfusion.

Immunochemical characterization of rhesus proteins with antibodies raised against synthetic peptides.

PubMed

Hermand, P; Mouro, I; Huet, M; Bloy, C; Suyama, K; Goldstein, J; Cartron, J P; Bailly, P

1993-07-15

Rabbit polyclonal antibodies were raised against synthetic peptides corresponding to hydrophilic regions of the human Rhesus (Rh) IX cDNA-encoded polypeptide predicted to be extracellularly or intracellularly exposed in the topologic model of the Rh blood group protein. Four antibodies encompassing residues 33-45 (MPC1), 224-233 (MPC4), 390-404 (MPC6), and 408-416 (MPC8) were characterized and compared with a polyclonal anti-Rh protein obtained by immunization with purified Rh proteins. All antibodies had specificity for authentic Rh polypeptides and reacted on Western blot with Rh proteins immunoprecipitated with human monoclonal anti-RhD, -c, and -E. MPC1, but not the other antibodies, agglutinated all human erythrocytes except Rhnull and Rhmod cells, which either lack totally or are severely deficient in Rh proteins, respectively. Immunoblotting analysis with membrane proteins from common and rare variants showed that MPC1 and MPC8 reacted in Western blot with 32-Kd Rh polypeptides from all common red blood cells except those from Rhnull and Rhmod, indicating that peptide regions 33-45 and 408-416 may be common to several if not all Rh proteins, whatever the Rh blood group specificity. MPC4 reacted only with membrane preparations from cells carrying the E antigen, whereas MPC6 recognized preferentially the Rh proteins from E and Ee preparations, suggesting that the protein encoded by the RhIXb cDNA carries the E and/or e antigen(s). Immunoadsorption experiments using inside-out or right-side-out sealed vesicules from DccEE red blood cells as competing antigen showed that the MPC6 and MPC8 antibodies bound only to the cytoplasmic side of the erythrocyte membrane, thus providing evidence for the intracellular orientation of the C-terminal 27 residues of the Rh polypeptides. Attempts to transiently or stably express the Rh polypeptides. Attempts to transiently or stably express the Rh cDNA in eukaryotic cells were largely unsuccessful, suggesting that Rh antigen expression at the cell surface requires correct transport and/or folding of the Rh proteins, possibly as a complex with one-membrane proteins of the Rh cluster that are lacking in Rhnull cells.

The role of blood groups in the development of diabetes mellitus after gestational diabetes mellitus.

PubMed

Karagoz, Hatice; Erden, Abdulsamet; Ozer, Ozerhan; Esmeray, Kubra; Cetinkaya, Ali; Avci, Deniz; Karahan, Samet; Basak, Mustafa; Bulut, Kadir; Mutlu, Hasan; Simsek, Yasin

2015-01-01

Gestational diabetes mellitus (GDM) is a common condition that is defined as glucose intolerance of varying degree with onset or first recognition during pregnancy and it affects approximately 5% of all pregnancies all over the world. GDM is not only associated with adverse pregnancy outcomes such as macrosomia, dystocia, birth trauma, and metabolic complications in newborns, but it is also a strong predictor of transitioning to overt DM postpartum. The association of ABO blood groups with DM has been observed before in several epidemiological and genetic studies and resulted with inconsistent findings, but still there are not enough studies in the literature about the association of ABO blood groups with GDM. In this study, we aimed at investigating any possible relationship between the ABO blood group system and GDM and also the transitioning of GDM to overt DM postpartum, in Turkey. A total of 233 patients with GDM from Kayseri Training and Research Hospital between 2002 and 2012 were included in the study. The cases that have serologically determined blood groups and Rh factor in the hospital records were included in the study, and the patients with unknown blood groups were excluded. Patients were classified according to blood groups (A, B, AB, and O) and Rh status (+/-). GDM was diagnosed based on the glucose cut-points of the International Association of the Diabetes and Pregnancy Society Groups. The distributions of blood groups of the patients with GDM were compared with the distribution of blood groups of 17,314 healthy donors who were admitted to the Turkish Red Crescent Blood Service in our city in 2012. There was a significant difference between the patients with GDM and control group in terms of distribution of ABO blood groups. Blood group AB was found to be higher in the patients with GDM compared to the control group (P=0.029). When the patients were compared according to the development of DM, the ratio of group O was higher than others, while the ratio of group B was lower in the group developing DM (P=0.001). There was a significant difference between the groups - GDM patients with or without DM - in terms of distribution of ABO blood groups with Rh factor and the ratio of developing DM is found to be higher in patients with +Rh factor among all the blood groups except for group B (P=0.008). In this study, we found a higher risk of GDM for the patients with blood group AB, which means that we have to be more careful on the follow-up of pregnant women with blood group AB. The patients with GDM of blood group O are under a higher risk of developing DM and also +Rh factor must be considered as another risk factor, so these patients should be closely followed postpartum by the oral glucose tolerance tests. To our knowledge, this is the first analysis that investigates the association between the ABO blood groups and transitioning to DM after GDM.

Application of a Multivariant, Caucasian-Specific, Genotyped Donor Panel for Performance Validation of MDmulticard®, ID-System®, and Scangel® RhD/ABO Serotyping

PubMed Central

Gassner, Christoph; Rainer, Esther; Pircher, Elfriede; Markut, Lydia; Körmöczi, Günther F.; Jungbauer, Christof; Wessin, Dietmar; Klinghofer, Roswitha; Schennach, Harald; Schwind, Peter; Schönitzer, Diether

2009-01-01

Summary Background Validations of routinely used serological typing methods require intense performance evaluations typically including large numbers of samples before routine application. However, such evaluations could be improved considering information about the frequency of standard blood groups and their variants. Methods Using RHD and ABO population genetic data, a Caucasian-specific donor panel was compiled for a performance comparison of the three RhD and ABO serological typing methods MDmulticard (Medion Diagnostics), ID-System (DiaMed) and ScanGel (Bio-Rad). The final test panel included standard and variant RHD and ABO genotypes, e.g. RhD categories, partial and weak RhDs, RhD DELs, and ABO samples, mainly to interpret weak serological reactivity for blood group A specificity. All samples were from individuals recorded in our local DNA blood group typing database. Results For ‘standard’ blood groups, results of performance were clearly interpretable for all three serological methods compared. However, when focusing on specific variant phenotypes, pronounced differences in reaction strengths and specificities were observed between them. Conclusions A genetically and ethnically predefined donor test panel consisting of 93 individual samples only, delivered highly significant results for serological performance comparisons. Such small panels offer impressive representative powers, higher as such based on statistical chances and large numbers only. PMID:21113264

Lack of any association between blood groups and lung cancer, independent of histology.

PubMed

Oguz, Arzu; Unal, Dilek; Tasdemir, Arzu; Karahan, Samet; Aykas, Fatma; Mutlu, Hasan; Cihan, Yasemin Benderli; Kanbay, Mehmet

2013-01-01

Lung cancer, the leading cause of cancer deaths, is divided into 2 main classes based on its biology, therapy and prognosis: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced stage at diagnosis, which is a major obstacle to improving outcomes. It is important to define the high risk group patients for early diagnosis and chance of cure. Blood group antigens are chemical components on erythrocyte membranes but they are also expressed on a variety of epithelial cells. Links between ABO blood groups with benign or malignant diseases, such as gastric and pancreas cancers, have been observed for a long time. In this study, we aimed to investigate any possible relationship between lung cancer histological subtypes and ABO-Rh blood groups. The files of 307 pathologically confirmed lung cancer patients were were reviewed retrospectively. Cases with a serologically determined blood group and Rh factor were included and those with a history of another primary cancer were excluded, leaving a total of 221. The distribution of blood groups of the lung cancer patients were compared with the distribution of blood groups of healthy donors admitted to the Turkish Red Crescent Blood Service in our city in the year 2012. There was no significant difference between patients with lung cancer of either type and the control group in terms of distribution of ABO blood groups and Rh factor (p: 0.073). There was also no relationship with non small cell cancer histological subtypes. In this study, we found no relationship between the ABO-Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first analysis of ABO blood groups in SCLC patients.

Distribution of ABO blood groups in the patients with intracranial aneurysm and association of different risk factors with particular blood type.

PubMed

Bir, Shyamal Chandra; Bollam, Papireddy; Nanda, Anil

2015-01-01

The association between ABO blood groups and intracranial aneurysms is not well-known. Many co-morbid factors are associated with intracranial aneurysms. Our objective was to assess the prevalence of different blood group in patients with intracranial aneurysm and to look for associations between risk factors and these groups. This retrospective study includes 1,491 cases who underwent surgical operations for intracranial aneurysms from 1993-2014. We have evaluated the information related to clinical history, ABO blood groups and associated risk factors in the patients both ruptured and unruptured intracranial aneurysms by chart review of the cases. In our study, out of 1,491 cases, the most common ABO blood groups were group O (668 cases, 44.80%) and Group A (603 cases, 40.44%), and Rh(+) in 1,319 (88.4%) and Rh(-) in 147 (11.6%). Blood Group A (43% vs. 36%) and Group B (16.2% vs. 8.6%) were significantly higher in Caucasian and African Americans respectively. However, in general population, there was no significant difference in blood groups between Caucasians and African Americans. Rh(-) factor was significantly higher in Caucasians compared to African Americans. Incidence of smoking was significantly higher in aneurysm patients with O group compared to others. In addition, incidence of hypercholesterolemia was significantly higher in aneurysm patients with A group compared to others. The racial disparity in the distribution of blood groups, and risk factor association with blood groups in the development of intracranial aneurysm needs to be considered. The findings from our study may be useful in identifying patients at increased risk. Further study may be required to establish the risks from multiple centers studies around the world.

Dynamics of lipoprotein level in blood plasma of pregnant women as a function of gestational age according to FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Korolik, E. V.; Korolenko, E. A.; Tretinnikov, O. N.; Kozlyakova, O. V.; Korolik, A. K.; Kirkovskiy, V. V.

2013-01-01

Results of an IR spectroscopic investigation of films of blood plasma taken from women of reproductive age, pregnant women with positive and negative Rh factors, and Rh-immunized women were presented as a function of gestational age. It was found that the lipoprotein content in blood plasma of all groups of pregnant women increased during the early stages of pregnancy (17-23 weeks) irrespective of the Rh factor and attained its peak value by weeks 30-35. It was shown that the lipoprotein level in blood plasma as a function of gestational age was quantitatively the same for pregnant women with positive and negative Rh factors. It was established for the first time that this dependence for Rh-immunized women featured a considerable increase of lipoprotein content at gestational age 30-32 weeks and declined acutely by week 36.

Evolution of two Rh blood group-related genes of the amphioxus species Branchiostoma floridae.

PubMed

Kitano, Takashi; Satou, Masahiro; Saitou, Naruya

2010-04-01

We determined cDNAs of two genes that belong to the Rhesus (Rh) blood group gene family in an amphioxus species (Branchiostoma floridae) and designated them Rh-related-1 (RhR-1) and Rh-related-2 (RhR-2). RhR-1 and RhR-2 consisted of 10 and 11 exons, respectively. 3' UTR sequences of RhR-1 were shorter (220-272 bp) than those of RhR-2 (1,505-1,650 bp). CDS lengths were 1,344 and 1,476 bp for RhR-1 and RhR-2, respectively, and the average nucleotide difference between their CDS regions was 0.33. The corresponding regions of Rh genes from exons 2 to 7 were relatively conserved among the chordate species examined in this study. Length difference numbers were in multiples of three, which implies that codon frames were conserved among them, and the same exon/intron boundary phases were observed in those regions. This region was used for the phylogenetic analyses. RhR-1 and RhR-2 formed a cluster on the phylogenetic tree of the Rh gene family. Gene duplication time of RhR-1 and RhR-2 was estimated to be ca. 500 million years ago. It is likely that the four Rh family genes in vertebrates emerged by gene duplications in the common ancestor of vertebrates, and functional differentiation has occurred after the first gene duplication.

Blood typing

MedlinePlus

... matching; Rh typing; ABO blood typing; Blood group; Anemia - immune hemolytic blood type; ABO blood type; A ... during pregnancy. Careful testing can prevent a severe anemia in the newborn and jaundice .

Are the blood groups of women with preeclampsia a risk factor for the development of hypertension postpartum?

PubMed

Avci, Deniz; Karagoz, Hatice; Ozer, Ozerhan; Esmeray, Kubra; Bulut, Kadir; Aykas, Fatma; Cetinkaya, Ali; Uslu, Emine; Karahan, Samet; Basak, Mustafa; Erden, Abdulsamet

2016-01-01

Preeclampsia (PE) is a pregnancy-related disorder characterized by hypertension (HT) and proteinuria noticeable after 20 weeks of gestation. PE is now considered as a cardiovascular disease risk factor and a number of studies have shown that experiencing PE increases the prevalence of various cardiovascular risk factors, such as metabolic syndrome and HT. In this study, we aimed to investigate any possible relationship between the ABO/Rh blood group system and PE in Turkey. In the second part of the study, we examined the relationship between the ABO blood group system and development of HT after PE. A total of 250 patients with PE from Kayseri Training and Research Hospital between 2002 and 2012 were included in the study. Patients were classified according to blood groups (A, B, AB, and O) and Rh status (+/-). There was a significant difference between the patients with PE and the control group in terms of distribution of ABO blood groups and the percentage of group AB was found to be higher in patients with PE compared to the control group (P=0.029). The risk of developing PE was significantly higher in group AB than other blood groups (P=0.006). The risk of developing HT after PE was significantly higher in group O than other blood groups (P=0.004). In this study, we found that the patients with blood group AB have a higher risk for PE. The patients with PE of blood group O are at high risk of developing HT, and Rh factor was identified as another risk at this point and these patients should be closely followed postpartum.

Influence of the Rh (D) blood group system on graft survival in renal transplantation.

PubMed

Bryan, C F; Mitchell, S I; Lin, H M; Nelson, P W; Shield, C F; Luger, A M; Pierce, G E; Ross, G; Warady, B A; Aeder, M I; Helling, T S; Landreneau, M D; Harrell, K M

1998-02-27

The Rh (D) blood group system has not traditionally been considered to be a clinically relevant histocompatibility barrier in transplantation since conflicting results of its clinical importance have been reported. We analyzed 786 consecutive primary cadaveric renal transplants performed by transplant centers in our Organ Procurement Organization (OPO) between 1990 and 1997. We also analyzed United Network for Organ Sharing (UNOS) data on 26,469 kidney transplants done from April 1994 to June 1996. Multivariate analysis revealed that Rh identity between the recipient and donor was significantly related to better graft outcome (risk ratio, 0.43; 95% confidence interval, 0.30 to 0.61; P=0.0001). Multivariate analysis of the UNOS data revealed that the Rh -/- group may have a positive influence on graft survival with a risk ratio of 0.43 (P=0.14). Multivariate analysis of primary cadaveric renal allografts performed within the Midwest Organ Bank OPO indicates that Rh (D) is a clinically relevant histocompatibility barrier that influences 7-year graft survival.

Administration of recombinant interleukin-11 improves the hemodynamic functions and decreases third space fluid loss in a porcine model of hemorrhagic shock and resuscitation.

PubMed

Honma, Kaneatsu; Koles, Nancy L; Alam, Hasan B; Rhee, Peter; Rollwagen, Florence M; Olsen, Cara; Keith, James C; Pollack, Matthew

2005-06-01

We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive sham hemorrhage (group I, sham); sham hemorrhage and 50 microg/kg rhIL-11 (group II, sham + IL-11); no drug (group III, saline); or 50 microg/kg rhIL-11 (group IV, IL-11). Blood and urine samples were obtained and analyzed at baseline, at the end of hemorrhaging, and thereafter once every hour. The pleural and peritoneal effusions were precisely quantified by using clinically accepted criteria. The mean arterial pressure (MAP) was higher postresuscitation (PR) in groups I, II, and IV (71.4 +/- 7.5 mmHg, 71.0 +/- 8.9 mmHg, and 72.9 +/- 12.3 mmHg, respectively) than in group III (59.9 +/- 10.9 mmHg), and the cardiac output of PR was higher in group IV (3.46 +/- 0.56 L/min) than in group III (2.99 +/- 0.62 L/min; P < 0.01). The difference in MAP between groups I and II became statistically significant at 40 min after rhIL-11 injection and such a difference persisted for 90 min. After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 +/- 325 mL and 1.0035, 82 +/- 21 mL) than in group III (958 +/- 390 mL and 1.0053, 125 +/- 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This strategy also significantly reduced the extent of third space fluid losses while also having a favorable impact on the intravascular volume status as evidenced by the improved urine output.

Frequencies of polymorphisms of the Rh, Kell, Kidd, Duffy and Diego systems of Santa Catarina, Southern Brazil.

PubMed

Costa, Daiane Cobianchi; Schinaider, Alessandra Arruda; Santos, Thais Mattos; Schörner, Everaldo José; Simon, Daniel; Maluf, Sharbel Weidner; de Moraes, Ana Carolina Rabello; Silva, Maria Claudia Silva

2016-01-01

Red blood cell genes are highly polymorphic with the distribution of alleles varying between different populations and ethnic groups. The objective of this study was to investigate gene polymorphisms of blood groups in the state of Santa Catarina, Southern Brazil. Three hundred and seventy-three unrelated blood donors and 31 transfusion-dependent patients were evaluated to investigate polymorphisms of the Rh, Kell, Duffy, Kidd, and Diego blood group systems in a population from the state of Santa Catarina. The subjects, from seven regions that comprise the blood-banking network of the state, were assessed between August 2011 and March 2014. The genotypes of the Rh, Kell, Duffy, Kidd, and Diego systems were determined using the restriction fragment length polymorphism-polymerase chain reaction and allele-specific polymerase chain reaction techniques. The genotype frequencies in this study were significantly different when populations from different regions of Santa Catarina were compared. Furthermore, there were also significant differences in the genetic frequencies compared to other Brazilian states. The genotype frequencies of the Kell and Kidd blood groups are similar to European populations from Naples, Italy and Zurich, Switzerland. This article reports for the first time the frequency of polymorphisms of blood group systems in blood donors from Santa Catarina, Southern Brazil. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

ABO blood groups and susceptibility to brucellosis.

PubMed

Mohsenpour, Behzad; Hajibagheri, Katayon; Afrasiabian, Shahla; Ghaderi, Ebrahim; Ghasembegloo, Saeideh

2015-01-01

The relationship between blood groups and some infections such as norovirus, cholera, and malaria has been reported. Despite the importance of brucellosis, there is a lack of data on the relationship between blood groups and brucellosis. Thus, in this study, we examined the relationship between blood groups and brucellosis. In this case-control study, the blood groups of 100 patients with brucellosis and 200 healthy individuals were studied. Exclusion criteria for the control group consisted of a positive Coombs Wright test or a history of brucellosis. The chi-square test was used to compare qualitative variables between the two groups. The variables that met inclusion criteria for the regression model were entered into the logistic regression model. A total of 43% patients were female and 57% male; 27% were urban and 73% rural. Regression analysis showed that the likelihood of brucellosis infection was 6.26 times more in people with blood group AB than in those with blood group O (P<0.001). However, Rh type was not associated with brucellosis infection. Thus, there is a relationship between blood group and brucellosis. People with blood group AB were susceptible to brucellosis, but no difference was observed for brucellosis infection in terms of blood Rh type.

A research on relationship between ABO blood groups and body mass index among Turkish seafarers.

PubMed

Nas, Selçuk; Fışkın, Remzi

2017-01-01

The present study aims to investigate and to reveal the relationship between ABO blood groups and body mass index (BMI) and obesity among Turkish seafarers by using the health examination reports data obtained from 2009 to 2016. The data on age, gender, weight, height and blood groups obtained from 298,247 medical examination reports of Turkish seafarers were used with the official permission of Directorate General of Health for Border and Coastal Areas. Only 116,871 reports included blood group data. Regression and analysis of variance (ANOVA) tests were performed to survey relationship between variables. The results of the study were compared with other studies in the related literature. It has been revealed that AB Rh (-) group was associated the highest mean BMI value (mean: 25.952). It is suggested that seafarers with AB Rh (-) blood group, who have the highest mean BMI value, should pay special attention to their weight.

Measurement of RBC agglutination with microscopic cell image analysis in a microchannel chip.

PubMed

Cho, Chi Hyun; Kim, Ju Yeon; Nyeck, Agnes E; Lim, Chae Seung; Hur, Dae Sung; Chung, Chanil; Chang, Jun Keun; An, Seong Soo A; Shin, Sehyun

2014-01-01

Since Landsteiner's discovery of ABO blood groups, RBC agglutination has been one of the most important immunohematologic techniques for ABO and RhD blood groupings. The conventional RBC agglutination grading system for RhD blood typings relies on macroscopic reading, followed by the assignment of a grade ranging from (-) to (4+) to the degree of red blood cells clumping. However, with the new scoring method introduced in this report, microscopically captured cell images of agglutinated RBCs, placed in a microchannel chip, are used for analysis. Indeed, the cell images' pixel number first allows the differentiation of agglutinated and non-agglutinated red blood cells. Finally, the ratio of agglutinated RBCs per total RBC counts (CRAT) from 90 captured images is then calculated. During the trial, it was observed that the agglutinated group's CRAT was significantly higher (3.77-0.003) than that of the normal control (0). Based on these facts, it was established that the microchannel method was more suitable for the discrimination between agglutinated RBCs and non-agglutinated RhD negative, and thus more reliable for the grading of RBCs agglutination than the conventional method.

The abundance and organization of polypeptides associated with antigens of the Rh blood group system.

PubMed

Gardner, B; Anstee, D J; Mawby, W J; Tanner, M J; von dem Borne, A E

1991-06-01

Twelve murine monoclonal antibodies, which react with human red cells of common Rh phenotype but give weak or negative reactions with Rh null erythrocytes, were used in quantitative binding assays and competitive binding assays to investigate the abundance and organization of polypeptides involved in the expression of antigens of the Rh blood group system. Antibodies of the R6A-type (R6A, BRIC-69, BRIC-207) and the 2D10-type (MB-2D10, LA18.18, LA23.40) recognize related structures and 100,000-200,000 molecules of each antibody bind maximally to erythrocytes of common Rh phenotype. Antibodies of the BRIC-125 type (BRICs 32, 122, 125, 126, 168, 211) recognize structures that are unrelated to those recognized by R6A-type and 2D10-type antibodies and between 10,000 and 50,000 antibody molecules bind maximally to erythrocytes of the common Rh phenotype. The binding of antibodies of the R6A-type and the 2D10-type, but not of antibodies of the BRIC-125-type could be partially inhibited by human anti-D antibodies (polyclonal and monoclonal) and a murine anti-e-like antibody. These results are consistent with evidence (Moore & Green 1987; Avent et al., 1988b) that the Rh blood group antigens are associated with a complex that comprises two groups of related polypeptides of M(r) 30,000 and M(r) 35,000-100,000, respectively, and suggest that there are 1-2 x 10(5) copies of this complex per erythrocyte. The polypeptide recognized by antibodies of the BRIC-125 type is likely to be associated with this complex.

Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion.

PubMed

Ameen, Reem; Al Shemmari, Salem; Al-Bashir, Abdulaziz

2009-08-01

Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients. A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity. Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations. This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.

How right is left? Handedness modulates neural responses during morphosyntactic processing.

PubMed

Grey, Sarah; Tanner, Darren; van Hell, Janet G

2017-08-15

Most neurocognitive models of language processing generally assume population-wide homogeneity in the neural mechanisms used during language comprehension, yet individual differences are known to influence these neural mechanisms. In this study, we focus on handedness as an individual difference hypothesized to affect language comprehension. Left-handers and right-handers with a left-handed blood relative, or familial sinistrals, are hypothesized to process language differently than right-handers with no left-handed relatives (Hancock and Bever, 2013; Ullman, 2004). Yet, left-handers are often excluded from neurocognitive language research, and familial sinistrality in right-handers is often not taken into account. In the current study we used event-related potentials to test morphosyntactic processing in three groups that differed in their handedness profiles: left-handers (LH), right-handers with a left-handed blood relative (RH FS+), and right-handers with no reported left-handed blood relative (RH FS-; both right-handed groups were previously tested by Tanner and Van Hell, 2014). Results indicated that the RH FS- group showed only P600 responses during morphosyntactic processing whereas the LH and RH FS+ groups showed biphasic N400-P600 patterns. N400s in LH and RH FS+ groups are consistent with theories that associate left-handedness (self or familial) with increased reliance on lexical/semantic mechanisms during language processing. Inspection of individual-level results illustrated that variability in RH FS- individuals' morphosyntactic processing was remarkably low: most individuals were P600-dominant. In contrast, LH and RH FS+ individuals showed marked variability in brain responses, which was similar for both groups: half of individuals were N400-dominant and half were P600-dominant. Our findings have implications for neurocognitive models of language that have been largely formulated around data from only right-handers without accounting for familial sinistrality or including left-handers, and moreover highlight that there is systematic - and often ignored - variability in language processing outcomes in neurologically healthy populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface decoration of red blood cells with maleimidophenyl-polyethylene glycol facilitated by thiolation with iminothiolane: an approach to mask A, B, and D antigens to generate universal red blood cells.

PubMed

Nacharaju, Parimala; Boctor, Fouad N; Manjula, Belur N; Acharya, Seetharama A

2005-03-01

The surface decoration of red blood cells (RBCs) by polyethylene glycol (PEG) chains has been an approach developed to camouflage the blood group antigens from their antibodies. A PEGylation protocol, however, that can mask the antigens appropriately to inhibit the agglutination of RBCs with the respective antibodies is not available so far. A new approach for PEGylation of RBC membrane proteins has been designed with thiolation-mediated maleimide chemistry. The accessibility of the surface lysine residues of membrane proteins to bulky PEG reagents was increased by linking an extension arm carrying a thiol group. RBCs have been PEGylated by thiolation-mediated chemistry with maleimidophenyl-PEG (Mal-Phe-PEG) reagents of different chain lengths. Mal-Phe-PEG-5000 chains alone masked the most important antigens of the Rh system (C, c, E, e, and D) from their antibodies. The masking of the A and B antigens needed a combination of Mal-Phe-PEG-5000 and Mal-Phe-PEG-20000 chains to inhibit the agglutination of RBCs completely with anti-A or anti-B. Thiolation-mediated PEGylation of RBCs with Mal-Phe-PEG-5000 and Mal-Phe-PEG-20000 converts Group A Rh(D)+ and B Rh(D)+ RBCs into RBCs with serologic behavior comparable to Group O Rh(D)- RBCs that are considered as universal RBCs for transfusion.

Mice Expressing RHAG and RHD Human Blood Group Genes

PubMed Central

Goossens, Dominique; da Silva, Nelly; Metral, Sylvain; Cortes, Ulrich; Callebaut, Isabelle; Picot, Julien; Mouro-Chanteloup, Isabelle; Cartron, Jean-Pierre

2013-01-01

Anti-RhD prophylaxis of haemolytic disease of the fetus and newborn (HDFN) is highly effective, but as the suppressive mechanism remains uncertain, a mouse model would be of interest. Here we have generated transgenic mice expressing human RhAG and RhD erythrocyte membrane proteins in the presence and, for human RhAG, in the absence, of mouse Rhag. Human RhAG associates with mouse Rh but not mouse Rhag on red blood cells. In Rhag knockout mice transgenic for human RHAG, the mouse Rh protein is “rescued” (re-expressed), and co-immunoprecipitates with human RhAG, indicating the presence of hetero-complexes which associate mouse and human proteins. RhD antigen was expressed from a human RHD gene on a BAC or from RHD cDNA under control of β-globin regulatory elements. RhD was never observed alone, strongly indicative that its expression absolutely depends on the presence of transgenic human RhAG. This first expression of RhD in mice is an important step in the creation of a mouse model of RhD allo-immunisation and HDFN, in conjunction with the Rh-Rhag knockout mice we have developed previously. PMID:24260394

Evaluation of targeted exome sequencing for 28 protein-based blood group systems, including the homologous gene systems, for blood group genotyping.

PubMed

Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Millard, Glenda M; O'Brien, Helen; Roulis, Eileen V; Liew, Yew-Wah; Martin, Jacqueline R; McGrath, Kelli A; Powley, Tanya; Flower, Robert L; Hyland, Catherine A

2017-04-01

Blood group single nucleotide polymorphism genotyping probes for a limited range of polymorphisms. This study investigated whether massively parallel sequencing (also known as next-generation sequencing), with a targeted exome strategy, provides an extended blood group genotype and the extent to which massively parallel sequencing correctly genotypes in homologous gene systems, such as RH and MNS. Donor samples (n = 28) that were extensively phenotyped and genotyped using single nucleotide polymorphism typing, were analyzed using the TruSight One Sequencing Panel and MiSeq platform. Genes for 28 protein-based blood group systems, GATA1, and KLF1 were analyzed. Copy number variation analysis was used to characterize complex structural variants in the GYPC and RH systems. The average sequencing depth per target region was 66.2 ± 39.8. Each sample harbored on average 43 ± 9 variants, of which 10 ± 3 were used for genotyping. For the 28 samples, massively parallel sequencing variant sequences correctly matched expected sequences based on single nucleotide polymorphism genotyping data. Copy number variation analysis defined the Rh C/c alleles and complex RHD hybrids. Hybrid RHD*D-CE-D variants were correctly identified, but copy number variation analysis did not confidently distinguish between D and CE exon deletion versus rearrangement. The targeted exome sequencing strategy employed extended the range of blood group genotypes detected compared with single nucleotide polymorphism typing. This single-test format included detection of complex MNS hybrid cases and, with copy number variation analysis, defined RH hybrid genes along with the RHCE*C allele hitherto difficult to resolve by variant detection. The approach is economical compared with whole-genome sequencing and is suitable for a red blood cell reference laboratory setting. © 2017 AABB.

[Association of abo blood groups with gestational diabetes mellitus].

PubMed

Huidobro M, Andrea; Torres C, Demetrio; Paredes, Fabio

2017-04-01

ABO and Rhesus blood systems are associated with type 2 Diabetes Mellitus (DM2). Gestational Diabetes (GDM) is a model to study DM. To study the association between GDM and ABO and Rhesus groups. A retrospective cohort study was performed in 1,078 women who gave birth to a singleton in Talca Regional Hospital, Chile, during 2008. We analyzed personal, obstetric, medical data and ABO and Rh blood groups. GDM was diagnosed in 6.6% of women. Age and body mass index were significantly associated with GDM. There were no differences in Rh blood groups (p = 0.604), while ABO groups were different between GDM and controls. B antigen was present in 3% of GDM women and in 10.8% of controls (p = 0.037), with an odds ratio of 0.25 after adjusting for other associated risk factors (p = 0.06). ABO group is suggested as a possible protector marker for GDM.

Cetrorelix suppresses the preovulatory LH surge and ovulation induced by ovulation-inducing factor (OIF) present in llama seminal plasma.

PubMed

Silva, Mauricio E; Smulders, Juan P; Guerra, Monserrat; Valderrama, Ximena P; Letelier, Claudia; Adams, Gregg P; Ratto, Marcelo H

2011-05-30

The purpose of the study was to determine if the effect of llama OIF on LH secretion is mediated by stimulation of the hypothalamus or pituitary gland. Using a 2-by-2 factorial design to examine the effects of OIF vs GnRH with or without a GnRH antagonist, llamas with a growing ovarian follicle greater than or equal to 8 mm were assigned randomly to four groups (n = 7 per group) and a) pre-treated with 1.5 mg of GnRH antagonist (cetrorelix acetate) followed by 1 mg of purified llama OIF, b) pre-treated with 1.5 mg of cetrorelix followed by 50 micrograms of GnRH, c) pre-treated with a placebo (2 ml of saline) followed by 1 mg of purified llama OIF or d) pre-treated with a placebo (2 ml of saline) followed by 50 micrograms of GnRH. Pre-treatment with cetrorelix or saline was given as a single slow intravenous dose 2 hours before intramuscular administration of either GnRH or OIF. Blood samples for LH measurement were taken every 15 minutes from 1.5 hours before to 8 hours after treatment. The ovaries were examined by ultrasonography to detect ovulation and CL formation. Blood samples for progesterone measurement were taken every-other-day from Day 0 (day of treatment) to Day 16. Ovulation rate was not different (P = 0.89) between placebo+GnRH (86%) and placebo+OIF groups (100%); however, no ovulations were detected in llamas pre-treated with cetrorelix. Plasma LH concentrations surged (P < 0.01) after treatment in both placebo+OIF and placebo+GnRH groups, but not in the cetrorelix groups. Maximum plasma LH concentrations and CL diameter profiles did not differ between the placebo-treated groups, but plasma progesterone concentrations were higher (P < 0.05), on days 6, 8 and 12 after treatment, in the OIF- vs GnRH-treated group. Cetrorelix (GnRH antagonist) inhibited the preovulatory LH surge induced by OIF in llamas suggesting that LH secretion is modulated by a direct or indirect effect of OIF on GnRH neurons in the hypothalamus.

Cheiloscopy and blood groups: Aid in forensic identification.

PubMed

Karim, Bushra; Gupta, Devanand

2014-10-01

Every person has certain features that make them radically distinct from others. One such feature is lip prints. Lip prints remain the same throughout life and are uninfluenced by injuries, diseases, or environmental changes. Different individuals have specific blood groups according to the various antigen-antibody reactions in their bloodstream. To determine the distribution of different patterns of lip prints among subjects having different ABO and Rh blood groups. To determine the correlation between respective characteristics of subjects. In this study, lip prints were obtained from 122 subjects (62 males and 60 females), and associated blood-group matching was performed to determine the predominant lip print type and to determine any correlation between lip print types and blood groups. Tsuchihashi's classification of type I (complete vertical grooves), type I' (incomplete vertical grooves), type II (forking grooves), type III (intersecting grooves), type IV (reticular grooves), and type V (indeterminate grooves) was used to compare with the ABO and Rh blood grouping systems. No correlation was found between lip prints and blood groups. No significant correlation exists between blood group and lip prints. Lip prints play a vital role in identification because they are unique.

How good is the obesity associated with blood groups in a cohort of female university going students?

PubMed

Jawed, Shireen; Atta, Komal; Tariq, Saba; Amir, Farah

2018-01-01

To find out frequency of obesity in female University students in Faisalabad and to investigate its association with blood groups of ABO system. A cross sectional study was conducted with a sample size of 200 female University students, recruited from the Faisalabad based institutes from May 2017 to July 2017. Relevant information was taken by administering questionnaire. Height in meters and weight in kg were taken by stadiometer. BMI was calculated using formula BMI=weight in kg/height m 2 . Blood groups were determined by classic (antigen-antibody agglutination test). The data was analyzed through SPSS 20. Descriptive were presented as mean± SD and association of BMI with blood groups was assessed by regression analysis. P value ≤0.05 deemed statistically significant. Out of students, 192 attempted the questionnaire and participated in study (96% response rate), 30% of the 192 females were obese, distribution of ABO blood group showed 43%, followed by O, A and AB. 90% were Rh positive and 10% were Rh negative. Blood group O showed a trend towards obesity and blood group AB showed a trend towards lean body. The blood group O showed the significant positive association with obesity. Population with blood group O showed greatest susceptibility to be overweight and obese.

Association of ABO and Rh blood groups with breast cancer.

PubMed

Meo, Sultan Ayoub; Suraya, Faryal; Jamil, Badar; Rouq, Fwziah Al; Meo, Anusha Sultan; Sattar, Kamran; Ansari, Mohammad Javed; Alasiri, Saleh A

2017-11-01

The aim of this study was to determine the association of "ABO" and "Rhesus" blood groups with incidence of breast cancer. In this study, we identified 70 research documents from data based search engines including "PubMed", "ISI-Web of Knowledge", "Embase" and "Google Scholar". The research papers were selected by using the primary key-terms including "ABO blood type", "Rhesus" blood type and "breast cancer". The research documents in which "ABO" and "Rhesus" blood types and breast cancer was debated were included. After screening, we reviewed 32 papers and finally we selected 25 research papers which met the inclusion criteria and remaining documents were excluded. Blood group "A" has high incidence of breast cancer (45.88%), blood group "O" has (31.69%); "B" (16.16%) and blood group "AB" has (6.27%) incidence of breast cancer. Blood group "A" has highest and blood group "AB" has least association with breast cancer. Furthermore, "Rhesus +ve" blood group has high incidence of breast cancer (88.31%) and "Rhesus -ve" blood group has least association with breast cancer (11.68%). Blood group "A" and "Rhesus +ve" have high risk of breast cancer, while blood type "AB" and "Rhesus -ve" are at low peril of breast cancer. Physicians should carefully monitor the females with blood group "A" and "Rh +ve" as these females are more prone to develop breast cancer. To reduce breast cancer incidence and its burden, preventive and screening programs for breast cancer especially in young women are highly recommended.

Blood groups and acute aortic dissection type III.

PubMed

Fatic, Nikola; Nikolic, Aleksandar; Vukmirovic, Mihailo; Radojevic, Nemanja; Zornic, Nenad; Banzic, Igor; Ilic, Nikola; Kostic, Dusan; Pajovic, Bogdan

2017-04-01

Acute aortic type III dissection is one of the most catastrophic events, with in-hospital mortality ranging between 10% and 12%. The majority of patients are treated medically, but complicated dissections, which represent 15% to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR). For the best outcomes adequate blood transfusion support is required. Interest in the relationship between blood type and vascular disease has been established. The aim of our study is to evaluate distribution of blood groups among patients with acute aortic type III dissection and to identify any kind of relationship between blood type and patient's survival. From January 2005 to December 2014, 115 patients with acute aortic type III dissection were enrolled at the Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia and retrospectively analyzed. Patients were separated into two groups. The examination group consisted of patients with a lethal outcome, and the control group consisted of patients who survived. The analysis of the blood groups and RhD typing between groups did not reveal a statistically significant difference ( p = 0.220). Our results indicated no difference between different blood groups and RhD typing with respect to in-hospital mortality of patients with acute aortic dissection type III.

Placental Growth Factor Reduces Blood Pressure in a Uteroplacental Ischemia Model of Preeclampsia in Nonhuman Primates.

PubMed

Makris, Angela; Yeung, Kristen R; Lim, Shirlene M; Sunderland, Neroli; Heffernan, Scott; Thompson, John F; Iliopoulos, Jim; Killingsworth, Murray C; Yong, Jim; Xu, Bei; Ogle, Robert F; Thadhani, Ravi; Karumanchi, S Ananth; Hennessy, Annemarie

2016-06-01

An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia because of endothelial dysfunction. Circulating soluble fms-like tyrosine kinase 1 (sFLT-1) increases and placental growth factor (PlGF) reduces before and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a nonhuman primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of a 182-day pregnancy). Two weeks after uteroplacental ischemia, rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100 μg/kg per day) for 5 days. Blood pressure was monitored by intra-arterial radiotelemetry and sFLT-1 and PlGF by ELISA. Uteroplacental ischemia resulted in experimental preeclampsia evidenced by increased blood pressure, proteinuria, and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after uteroplacental ischemia. rhPlGF reduced systolic blood pressure in the treated group (-5.2±0.8 mm Hg; from 132.6±6.6 mm Hg to 124.1±7.6 mm Hg) compared with an increase in systolic blood pressure in controls (6.5±3 mm Hg; from 131.3±1.5 mm Hg to 138.6±1.5 mm Hg). Proteinuria reduced in the treated group (-72.7±55.7 mg/mmol) but increased in the control group. Circulating levels of total sFLT-1 were not affected by the administration of PlGF; however, a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference between the weights or lengths of the neonates in the rhPlGF or control group; however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. © 2016 American Heart Association, Inc.

ABO, Rhesus, and Kell Antigens, Alleles, and Haplotypes in West Bengal, India

PubMed Central

Basu, Debapriya; Datta, Suvro Sankha; Montemayor, Celina; Bhattacharya, Prasun; Mukherjee, Krishnendu; Flegel, Willy A.

2018-01-01

Background Few studies have documented the blood group antigens in the population of eastern India. Frequencies of some common alleles and haplotypes were unknown. We describe phenotype, allele, and haplotype frequencies in the state of West Bengal, India. Methods We tested 1,528 blood donors at the Medical College Hospital, Kolkata. The common antigens of the ABO, Rhesus, and Kell blood group systems were determined by standard serologic methods in tubes. Allele and haplotype frequencies were calculated with an iterative method that yielded maximum-likelihood estimates under the assumption of a Hardy-Weinberg equilibrium. Results The prevalence of ABO antigens were B (34%), O (32%), A (25%), and AB (9%) with ABO allele frequencies for O = 0.567, A = 0.189, and B = 0.244. The D antigen (RH1) was observed in 96.6% of the blood donors with RH haplotype frequencies, such as for CDe = 0.688809, cde = 0.16983 and CdE = 0.000654. The K antigen (K1) was observed in 12 donors (0.79%) with KEL allele frequencies for K = 0.004 and k = 0.996. Conclusions: For the Bengali population living in the south of West Bengal, we established the frequencies of the major clinically relevant antigens in the ABO, Rhesus, and Kell blood group systems and derived estimates for the underlying ABO and KEL alleles and RH haplotypes. Such blood donor screening will improve the availability of compatible red cell units for transfusion. Our approach using widely available routine methods can readily be applied in other regions, where the sufficient supply of blood typed for the Rh and K antigens is lacking. PMID:29593462

Evaluation of immunohematologic routine methods using the new erythrocyte-magnetized technology on the QWALYS 2 system.

PubMed

Schoenfeld, Helge; Bulling, Katia; von Heymann, Christian; Neuner, Bruno; Kalus, Ulrich; Kiesewetter, Holger; Pruss, Axel

2009-07-01

QWALYS 2 is a fully automated system for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS). Its new erythrocyte-magnetized technology (EMT) is based on the use of magnetic nanoparticles and avoids centrifugation and washing steps. Overall 499 blood samples were tested with our routine blood bank methods for ABO/D grouping, 313 samples for Rh phenotyping and K typing (microtiter plates; Olympus PK 7200), and 478 samples for ABS (gel centrifugation technique, DiaMed). All samples were tested in parallel with the EMT. In 496 of 499 samples (99.4%), a complete concordance between the observed (QWALYS 2) and the expected results for ABO/D grouping was found. One sample with a weak A in an AB blood group and 2 samples with a weak D were not detected by the QWALYS system. Rh phenotyping and K tests revealed a 100% concordance. In the two ABS techniques, 427 samples were negative in both and 15 samples showed the same antibody specificity in both. Three immunoglobulin M antibodies were as expected negative in EMT and positive by DiaMed. In 32 cases (6.7%), false-positive reactions were observed by EMT due to 22 unspecific reactions (4.6%) and 10 lipemic or fibrinic plasmas (2.1%). One autoantibody was found by EMT only. The EMT is reliably suited to ABO/D grouping, Rh phenotyping, and K testing and is suitable to detect immunoglobulin G red blood cell alloantibodies as well. The rate of false-positive reactions in ABS due to lipemic and fibrinic samples needs to be reduced.

Association between Cheiloscopic Patterns and ABO Blood Groups among South Indian Population.

PubMed

Khanapure, Sneha; Suhas, H G; Potdar, Shrudha; Sam, George; Sudeep, C B; Arjun, M R

2017-07-01

Human beings have few characteristics that are unique from others. Lip prints are one of such feature. They are not changed throughout the life and are not influenced by injuries, diseases, or environmental changes. According to the various antigen-antibody reactions in the bloodstream, different individuals have specific blood groups. To study the distribution of lip print patterns among individuals with different ABO and Rh blood groups and also to know the relation between their characters and blood groups. In the present study, lip prints were collected randomly from 85 individuals, and their blood group matching was performed. This is to identify the most common lip print type and to know any association between lip print types and blood groups. Tsuchihashi's classification of lip prints was used to compare with the ABO and Rh blood grouping systems. It was observed that in individuals with B+, A+, and O- blood groups, predominant pattern was Type IV and individuals having blood group O+ and AB+ common lip print pattern was Type II. This study showed strong association between lip print patterns and ABO blood groups as some blood groups were not included in statistical analysis; further studies including larger sample are essential to substantiate the results. Correlating lip print with blood group helps in identification of the suspects. Along with lip prints, another biological record that remains unchanged throughout the lifetime of a person is the blood group. Determining the blood group of a person from the samples obtained at the site of crime and also recovering lip prints from site can help identify a person.

Validation of a hospital-laboratory workstation for immunohematologic methods.

PubMed

Schoenfeld, Helge; Pretzel, Karin J; von Heymann, Christian; Neuner, Bruno; Kalus, Ulrich; Kiesewetter, Holger; Pruss, Axel

2010-01-01

The FREELYS Nano system (Diagast) is a manual workstation for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS) for immunoglobulin G (IgG) antibodies only and works with the erythrocyte-magnetized technology (EMT). The principle of EMT is based on magnetization of red blood cells and avoids centrifugation and washing steps. A total of 304 samples were tested with our routine blood bank methods, 100 samples for ABO/D grouping, 196 samples (100 at first evaluation, 96 at second evaluation) for Rh phenotyping and K typing (PK7200, Olympus), and 108 samples for ABS (DiaMed). All samples were tested in parallel with the FREELYS Nano. We found a 100% concordance between the observed (FREELYS Nano) and the expected (Olympus PK7200) results for ABO/D grouping in all 100 samples. For Rh phenotyping and K tests, in 24 of 100 samples false-positive reactions were observed in the first evaluation by the FREELYS Nano. After changing the test kit batch for Rh phenotyping by the manufacturer, a complete concordance in Rh phenotyping and K tests was observed in a second evaluation. For ABS, the FREELYS Nano showed in 4 of 108 samples (3.7%) false-negative reactions for IgG antibodies (two anti-K, one anti-E, one anti-C(w)), and one (0.9%) false-positive reaction. The FREELYS Nano is reliably suited to ABO/D grouping, Rh phenotyping, and K testing. The rate of false-negative reactions for IgG antibodies should be reduced.

JAL (RH48) blood group antigen: serologic observations

PubMed Central

Lomas-Francis, Christine; Alcantara, Denden; Westhoff, Connie; Uehlinger, Joan; Valvasori, Marilia; Castilho, Lillian; Reid, Marion E.

2009-01-01

BACKGROUND JAL (RH48) is a low-prevalence antigen in the Rh blood group system and anti-JAL has caused hemolytic disease of the newborn. JAL is associated with either a haplotype carrying depressed C and e antigens or one carrying depressed c and e antigens. Blood samples from JAL+ people were tested, published serologic findings were confirmed, serologic studies were extended to include expression of other Rh antigens, and the antibody specificities produced by three sensitized JAL+ probands are reported. STUDY DESIGN AND METHODS Red blood cell (RBC) samples from 17 (12 probands) JAL+ persons were tested by hemagglutination using standard methods. RESULTS RBCs from both the Caucasian JAL+ probands had the (C)(e) haplotype and weakened C, e, hrB, and hrS antigens. JAL+ samples from black persons had the (c)(e) haplotype and expressed weakened c, e, f, V, VS, hrB, and hrS antigens. Plasma from three sensitized c+e+ JAL+ probands contained alloanti-c, alloanti-e, or alloantibody of apparent anti-Rh17 specificity. This study shows that this alloanti-Rh17–like antibody recognizes the high-prevalence antigen antithetical to JAL that has been named CEST. CONCLUSIONS The presence of the JAL antigen has a quantitative (weakening) effect on the expression of C, e, hrB, and hrS antigens in Caucasian persons and of c, e, f, V, VS, hrB, and hrS antigens in people of black African ancestry. A qualitative effect also was demonstrated by the presence of alloanti-c or alloanti-e in the plasma of two transfused c+e+ patients and by an antibody (anti-CEST) that recognizes the high-prevalence antigen antithetical to JAL. PMID:19192256

21 CFR 606.121 - Container label.

Code of Federal Regulations, 2011 CFR

2011-04-01

... payment for a blood donation. (ii) A volunteer donor is a person who does not receive monetary payment for... units of Red Blood Cells, the volume of the product, accurate to within ±10 percent; or optionally for.... The Rh group shall be designated as follows: (i) If the test using Anti-D Blood Grouping Reagent is...

21 CFR 606.121 - Container label.

Code of Federal Regulations, 2010 CFR

2010-04-01

... payment for a blood donation. (ii) A volunteer donor is a person who does not receive monetary payment for... units of Red Blood Cells, the volume of the product, accurate to within ±10 percent; or optionally for.... The Rh group shall be designated as follows: (i) If the test using Anti-D Blood Grouping Reagent is...

Matrix-assisted laser desorption/ionisation, time-of-flight mass spectrometry-based blood group genotyping--the alternative approach.

PubMed

Gassner, Christoph; Meyer, Stefan; Frey, Beat M; Vollmert, Caren

2013-01-01

Although matrix-assisted laser desorption/ionisation, time-of-flight mass spectrometry (MALDI-TOF MS) has previously been reported for high throughput blood group genotyping, those reports are limited to only a few blood group systems. This review describes the development of a large cooperative Swiss-German project, aiming to employ MALDI-TOF MS for the molecular detection of the blood groups Rh, Kell, Kidd, Duffy, MNSs, a comprehensive collection of low incidence antigens, as well as the platelet and granulocyte antigens HPA and HNA, representing a total of 101 blood group antigens, encoded by 170 alleles, respectively. Recent reports describe MALDI-TOF MS as a technology with short time-to-resolution, ability for high throughput, and cost-efficiency when used in genetic analysis, including forensics, pharmacogenetics, oncology and hematology. Furthermore, Kell and RhD genotyping have been performed on fetal DNA from maternal plasma with excellent results. In summary, this article introduces a new technological approach for high throughput blood group genotyping by means of MALDI-TOF MS. Although all data presented are preliminary, the observed success rates, data quality and concordance with known blood group types are highly impressive, underlining the accuracy and reliability of this cost-efficient high throughput method. Copyright © 2013 Elsevier Inc. All rights reserved.

Rh Incompatibility

MedlinePlus

... type is called Rh. Rh factor is a protein on red blood cells. Most people are Rh-positive; they have Rh factor. Rh-negative people don't have it. Rh factor is inherited though genes. When you're pregnant, blood from your baby can cross into your ...

Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients.

PubMed

Dhawan, Hari Krishan; Kumawat, Vijay; Marwaha, Neelam; Sharma, Ratti Ram; Sachdev, Suchet; Bansal, Deepak; Marwaha, Ram Kumar; Arora, Satyam

2014-07-01

The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards. Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-C(w) = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization.

Association of ABO and Rh Blood Groups to Blood-Borne Infections among Blood Donors in Tehran-Iran

PubMed Central

MOHAMMADALI, Fatemeh; POURFATHOLLAH, Aliakbar

2014-01-01

Abstract Background The aim of this study was to investigate the prevalence of hepatitis B, hepatitis C, HIV and syphilis infections in blood donors referred to Tehran Blood Transfusion Center (TBTC), and determine any association between blood groups and blood- borne infections between the years of 2005 and 2011. Methods This was a retrospective study conducted at TBTC. All of the donor serum samples were screened for HBV, HCV, HIV and syphilis by using third generation ELISA kits and RPR test. Initial reactive samples were tested in duplicate. Confirmatory tests were performed on all repeatedly reactive donations. Blood group was determined by forward and reverse blood grouping. The results were subjected to chi square analysis for determination of statistical difference between the values among different categories according to SPSS program. Results Overall, 2031451 donor serum samples were collected in 2005-2011. Totally, 10451 were positive test for HBV, HCV, HIV and syphilis. The overall seroprevalence of HBV, HCV, HIV, and syphilis was 0.39%, 0.11%, 0.005%, and 0.010%, respectively. Hepatitis B and HIV infections were significantly associated with blood group of donors (P <0.05) ; percentage of HIV Ag/Ab was higher in donors who had blood group “A” and percentage of HBs Ag was lower in donors who had blood group O. There was no significant association between Hepatitis C and syphilis infections with ABO and Rh blood groups (P>0.05). Conclusion Compared with neighboring countries and the international standards, prevalence of blood-borne infections is relatively low. PMID:25909065

Association of ABO and Rh Blood Groups to Blood-Borne Infections among Blood Donors in Tehran-Iran.

PubMed

Mohammadali, Fatemeh; Pourfathollah, Aliakbar

2014-07-01

The aim of this study was to investigate the prevalence of hepatitis B, hepatitis C, HIV and syphilis infections in blood donors referred to Tehran Blood Transfusion Center (TBTC), and determine any association between blood groups and blood- borne infections between the years of 2005 and 2011. This was a retrospective study conducted at TBTC. All of the donor serum samples were screened for HBV, HCV, HIV and syphilis by using third generation ELISA kits and RPR test. Initial reactive samples were tested in duplicate. Confirmatory tests were performed on all repeatedly reactive donations. Blood group was determined by forward and reverse blood grouping. The results were subjected to chi square analysis for determination of statistical difference between the values among different categories according to SPSS program. Overall, 2031451 donor serum samples were collected in 2005-2011. Totally, 10451 were positive test for HBV, HCV, HIV and syphilis. The overall seroprevalence of HBV, HCV, HIV, and syphilis was 0.39%, 0.11%, 0.005%, and 0.010%, respectively. Hepatitis B and HIV infections were significantly associated with blood group of donors (P <0.05) ; percentage of HIV Ag/Ab was higher in donors who had blood group "A" and percentage of HBs Ag was lower in donors who had blood group O. There was no significant association between Hepatitis C and syphilis infections with ABO and Rh blood groups (P>0.05). Compared with neighboring countries and the international standards, prevalence of blood-borne infections is relatively low.

Evaluation of new indigenous "point-of-care" ABO and Rh grouping device.

PubMed

Tiwari, Aseem Kumar; Setya, Divya; Aggarwal, Geet; Arora, Dinesh; Dara, Ravi C; Ratan, Ankita; Bhardwaj, Gunjan; Acharya, Devi Prasad

2018-01-01

Erycard 2.0 is a "point-of-care" device that is primarily being used for patient blood grouping before transfusion. Erycard 2.0 was compared with conventional slide technology for accuracy and time taken for ABO and Rh forward grouping result with column agglutination technology (CAT) being the gold standard. Erycard 2.0 as a device was also evaluated for its stability under different storage conditions and stability of result till 48 h. In addition, grouping of hemolyzed samples was also tested with Erycard 2.0. Ease of use of Erycard 2.0 was evaluated with a survey among paramedical staff. Erycard 2.0 demonstrated 100% concordance with CAT as compared with slide technique (98.9%). Mean time taken per test by Erycard 2.0 and slide technique was 5.13 min and 1.7 min, respectively. After pretesting storage under different temperature and humidity conditions, Erycard 2.0 did not show any deviation from the result. The result did not change even after 48 h of testing and storage under room temperature. 100% concordance was recorded between pre- and post-hemolyzed blood grouping. Ease of use survey revealed that Erycard 2.0 was more acceptable to paramedical staff for its simplicity, objectivity, and performance than conventional slide technique. Erycard 2.0 can be used as "point-of-care" device for blood donor screening for ABO and Rh blood group and can possibly replace conventional slide technique.

Evaluation of new indigenous “point-of-care” ABO and Rh grouping device

PubMed Central

Tiwari, Aseem Kumar; Setya, Divya; Aggarwal, Geet; Arora, Dinesh; Dara, Ravi C.; Ratan, Ankita; Bhardwaj, Gunjan; Acharya, Devi Prasad

2018-01-01

BACKGROUND: Erycard 2.0 is a “point-of-care” device that is primarily being used for patient blood grouping before transfusion. MATERIALS AND METHODS: Erycard 2.0 was compared with conventional slide technology for accuracy and time taken for ABO and Rh forward grouping result with column agglutination technology (CAT) being the gold standard. Erycard 2.0 as a device was also evaluated for its stability under different storage conditions and stability of result till 48 h. In addition, grouping of hemolyzed samples was also tested with Erycard 2.0. Ease of use of Erycard 2.0 was evaluated with a survey among paramedical staff. RESULTS: Erycard 2.0 demonstrated 100% concordance with CAT as compared with slide technique (98.9%). Mean time taken per test by Erycard 2.0 and slide technique was 5.13 min and 1.7 min, respectively. After pretesting storage under different temperature and humidity conditions, Erycard 2.0 did not show any deviation from the result. The result did not change even after 48 h of testing and storage under room temperature. 100% concordance was recorded between pre- and post-hemolyzed blood grouping. Ease of use survey revealed that Erycard 2.0 was more acceptable to paramedical staff for its simplicity, objectivity, and performance than conventional slide technique. CONCLUSION: Erycard 2.0 can be used as “point-of-care” device for blood donor screening for ABO and Rh blood group and can possibly replace conventional slide technique. PMID:29403211

Noninvasive fetal RhCE genotyping from maternal blood.

PubMed

Geifman-Holtzman, O; Grotegut, C A; Gaughan, J P; Holtzman, E J; Floro, C; Hernandez, E

2009-01-01

The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA. To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used. English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966-2007), Ovid (1966-2007), CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation. A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded. From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy. We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was consistently the best source of fetal RhCE genotyping in 147/147 (100%) for RhC/c and 168/168 (100%) for RhE/e. The combined accuracy of noninvasive fetal RhC/c or RhE/e determination using maternal peripheral blood is 96.3% and 98.2%, respectively. FfDNA in maternal plasma is a better source for genotyping reported to be 100% correct for both RHCE genotypes. Further studies and reports of accuracy from laboratories performing the tests are required before prenatal determination of fetal RhC/c or RhE/e genotypes from maternal blood can safely replace the current methods used in the management of the RhC/c or RhE alloimmunised pregnancies.

Effect of Bovine Serum Albumin Treatment on the Aging and Activity of Antibodies in Paper Diagnostics.

PubMed

Huang, Ziwei; Gengenbach, Thomas; Tian, Junfei; Shen, Wei; Garnier, Gil

2018-01-01

Paper and cellulosic films are used in many designs of low-cost diagnostics such as paper-based blood grouping devices. A major issue limiting their commercialization is the short stability of the functional biomolecules. To address this problem, the effect of relative humidity (RH) and bovine serum albumin (BSA) on the antibody bioactivity and the surface chemical composition of a paper blood typing biodiagnostic were studied. An IgM blood typing antibody was physisorbed from solution onto paper - with or without BSA pretreatment, and aged for periods up to 9 weeks under various conditions with a series of RH. The blood typing efficiency of the antibodies and the substrate surface chemical composition were analyzed by image analysis and X-ray photoelectron spectroscopy (XPS), respectively. This study tests two hypotheses. The first is that the hydroxyl groups in paper promote antibody denaturation on paper; the second hypothesis is that proteins such as BSA can partially block the hydroxyl groups within paper, thus preserving antibody bioactivity. Results show that high RH is detrimental to antibody longevity on paper, while BSA can block hydroxyl groups and prolong antibody longevity by almost an order of magnitude-regardless of humidity. This study opens up new engineering concepts to develop robust and marketable paper diagnostics. The simplest is to store paper and antibody based diagnostics in moisture proof packages.

Effect of Bovine Serum Albumin Treatment on the Aging and Activity of Antibodies in Paper Diagnostics

NASA Astrophysics Data System (ADS)

Huang, Ziwei; Gengenbach, Thomas; Tian, Junfei; Shen, Wei; Garnier, Gil

2018-05-01

Paper and cellulosic films are used in many designs of low-cost diagnostics such as paper-based blood grouping devices. A major issue limiting their commercialization is the short stability of the functional biomolecules. To address this problem, the effect of relative humidity (RH) and bovine serum albumin (BSA) on the antibody bioactivity and the surface chemical composition of a paper blood typing biodiagnostic were studied. An IgM blood typing antibody was physisorbed from solution onto paper - with or without BSA pretreatment, and aged for periods up to 9 weeks at room temperature and under different RH conditions. The blood typing efficiency of the antibodies and the substrate surface chemical composition were analyzed by image analysis and X-ray photoelectron spectroscopy (XPS), respectively. This study tests two hypotheses. The first is that the hydroxyl groups in paper promote antibody denaturation on paper; the second hypothesis is that proteins such as BSA can partially block the hydroxyl groups with paper, thus preserving antibody bioactivity. Results show that high RH is detrimental to antibody longevity on paper, while BSA can block hydroxyl groups and prolong antibody longevity by almost an order of magnitude – regardless of humidity. This study opens up new engineering concepts to develop robust and marketable paper diagnostics. The simplest is to store paper and antibody based diagnostics in moisture proof packages.

Gonadotrophin-releasing hormone agonist combined with high-intensity focused ultrasound ablation for adenomyosis: a clinical study.

PubMed

Guo, Y; Duan, H; Cheng, J; Zhang, Y

2017-08-01

This study was to investigate the clinical efficacy of a gonadotrophin-releasing hormone agonist (GnRH-a) combined with high-intensity focused ultrasound (HIFU) ablation treatment for adenomyosis. A non-randomized prospective study. Gynaecological Minimally Invasive Centre in a single hospital. Patients with adenomyosis. Seventy-nine patients with adenomyosis were enrolled, including 55 patients in the control group treated with only HIFU and 24 patients in the study group treated with GnRH-a combined with HIFU. All the patients follow up 6 months after the HIFU procedure. The related parameters in the two groups were assessed before and 3 months as well as 6 months after treatment including serum levels of tumor marker and cytokine, volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrheal scores. Differences between the group treated with HIFU alone and the group treated with GnRH-a combined with HIFU. Before HIFU treatment, no significant difference was observed in serum levels of CA125, CA19-9, and interleukin-6 (IL-6), the volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrhea scores between the two groups. (P > 0.05). The serum CA125 levels significantly decreased in both groups after HIFU, but the serum CA125 levels in the study group were still significantly lower than those in the control group (P < 0.05). The volume of uterine and adenomyotic lesion significantly decreased in both groups after HIFU procedure, and decreased even more in the study group 3 and 6 months after treatment (P < 0.05). Dysmenorrhea scores and menstruation volumes significantly decreased in both groups after HIFU treatment. Moreover in the study group were significantly lower than those in the control group after 3 and 6 months (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. The short-term follow-up results indicate that the combination of GnRH-a and HIFU treatment significantly decreased serum CA125 levels, volumes of uterine, adenomyotic lesion and menstrual blood, as well as dysmenorrhea scores, and improved the clinical outcomes compared with the HIFU ablation alone in patients with adenomyosis. However, the further follow-up is needed to explore the long-term effects. A combination of GnRH-a with HIFU in the treatment of adenomyosis significantly decreased serum CA125 levels, uterine and adenomyotic lesion volumes, dysmenorrhea scores, and menstrual blood volumes. © 2017 Royal College of Obstetricians and Gynaecologists.

ABO and Rhesus blood groups and risk of endometriosis in a French Caucasian population of 633 patients living in the same geographic area.

PubMed

Borghese, Bruno; Chartier, Mélanie; Souza, Carlos; Santulli, Pietro; Lafay-Pillet, Marie-Christine; de Ziegler, Dominique; Chapron, Charles

2014-01-01

The identification of epidemiological factors increasing the risk of endometriosis could shorten the time to diagnosis. Specific blood groups may be more common in patients with endometriosis. We designed a cross-sectional study of 633 Caucasian women living in the same geographic area. Study group included 311 patients with histologically proven endometriosis. Control group included 322 patients without endometriosis as checked during surgery. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses. We observed a higher proportion of Rh-negative women in the study group, as compared to healthy controls. Multivariate analysis showed that Rh-negative women are twice as likely to develop endometriosis (aOR = 1.90; 95% CI: 1.20-2.90). There was no significant difference in ABO group distribution between patients and controls. There was no difference when taking into account either the clinical forms (superficial endometriosis, endometrioma, and deep infiltration endometriosis) or the rAFS stages. Rh-negative women are twice as likely to develop endometriosis. Chromosome 1p, which contains the genes coding for the Rhesus, could also harbor endometriosis susceptibility genes.

INVESTIGATIONS ON THE OCCURRENCE OF Rh SUBSTANCES IN AMNIOTIC FLUID

PubMed Central

Witebsky, Ernest; Mohn, James F.

1945-01-01

1. Rh substances are found in amniotic fluid. Not all anti-Rh sera seem to be suitable for the detection of Rh substances in amniotic fluid. Careful selection of Rh antisera, as well as quantitative considerations, determine success or failure of their demonstration. 2. The baby's Rh type and not the mother's determines the occurrence of Rh substances in amniotic fluid. 3. There are Rh secretors and Rh non-secretors. At least four out of five individuals are secretors. 4. The secretion of Rh substance into the amniotic fluid would seem to be entirely independent of the secretion of the blood group specific substances. 5. The majority of Rh-positive amniotic fluids seem to contain both Rh1 and Rh2 substances. However, in certain instances fluids belonging to the pure Rh1 type or pure Rh2 type were found. 6. Three cases of erythroblastosis were described. All three came from Rh-negative mothers with Rh-positive babies. The amniotic fluids of all three failed to reveal the presence of Rh substances. PMID:19871489

Donors' blood group declaration before donation can be used as a tool for electronic crossmatching.

PubMed

Arslan, O

2005-12-01

Electronic crossmatching (E-XM) is used to detect ABO incompatibility. In developing countries, as many of the donations are from first-time donors, it is difficult to guarantee the accuracy of the ABO/Rh label on these units to use them for E-XM. This problem was overcome with a new software 'hemosoft', using donors' blood group declaration before donation as a tool for E-XM. During registration, donors either declare their blood group or give no comment. For, ABO/Rh grouping, either two results from different donations or only one in concordant with the declaration before donation is needed. If there is a conflict, second typing is performed from the unit segment. If donors give no declaration, two different technicians perform typing, one from the sample tube and the other from the unit segment. Of 18,618 donations performed, 640 (3%) were repeated and the rest were first-time donations. In 16,327, typing was performed once, as the blood group declaration and the typing results were identical. In 2407, grouping was performed twice, as donors gave no declaration or conflicts between declaration and typing results were found. No labelling or wrong unit-release errors were detected in units donated, typed and labelled in our centre. In 26,402 donations, 16,314 (61.8%) E-XMs were performed. No major haemolytic transfusion reaction was recorded. Donors' ABO/Rh declaration before donation can be used as a tool for E-XM, instead of the requirement for serological confirmation or a second donation to guarantee grouping.

Blood Group Antigens on HeLa Cells shown by Mixed Agglutination

PubMed Central

Kelus, A.; Gurner, B. W.; Coombs, R. R. A.

1959-01-01

The mixed agglutination reaction has been used for investigating the presence of blood group antigens on the surface of human cervical carcinoma cells (HeLa) cultured for eight years in vitro. The H antigen was demonstrated in the absence of A and B. The MN-type antigen has been found as well as Tja. Treatment of HeLa cells with ficin greatly enhanced the reaction of anti-H and anti-Tja with the corresponding antigens on HeLa cells. The authors failed to show the following antigens: Rh(D) and Rh(c), S, P, Lea, Leb, Lua and Lub. ImagesFIG. 1FIG. 2 PMID:14405338

Late onset neonatal anaemia due to maternal anti-Kp(b) induced haemolytic disease of the newborn.

PubMed

Elhence, Priti; Sachan, Deepti; Verma, Anupam; Kumar, Archana; Chaudhary, Rajendra

2012-12-01

Alloanti-Kp(b) is a rare, clinically significant antibody against high frequency red cell antigen Kp(b) of Kell blood group system. We report here a case of Haemolytic disease of newborn (HDN) due to anti-Kp(b), which manifested as severe anaemia at the age of 1 month. To diagnose and successfully manage anti-Kp(b) induced HDN. Direct antiglobulin test (DAT), antigen typing, irregular antibody screening and identification were done by polyspecific LISS Coombs Gel card and standard methods. At presentation the neonate had severe anemia with reticulocytopenia. Blood group was B, Rh D positive and DAT was 2+. Anti-Kp(b) was detected in mother's serum. Due to unavailability of Kp(b) negative red cells and incompatible blood group of mother (A(1)B Rh D positive) infant was transfused group B Rh D, Kp(b) positive PRBCs under steroid cover. He was symptom free at 4 months of age and DAT became negative at 6 months. Anti-Kp(b) is capable of causing severe late HDN. Infants born to irregular antibody positive mothers should be investigated and closely monitored for several weeks after birth for immune HDN even if asymptomatic at birth. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ultrasonographic and endocrine evaluation of three regimes for oestrus and ovulation synchronization for sheep in the subtropics.

PubMed

Ali, A; Hayder, M; Saifelnaser, E O H

2009-12-01

This study aimed to evaluate three regimes for oestrus and ovulation synchronization in Farafra ewes in the subtropics. During autumn, 43 ewes were assigned to (i) controlled internal drug releasing (CIDR)-eCG group, treated with CIDR for 12 days and eCG at insert withdrawal, n=13; (ii) PGF2alpha-PGF2alpha group, treated with two PGF2alpha injections at 11 days interval, n=14; and (iii) GnRH-PGF2alpha-GnRH group, treated with GnRH, followed 5 days later with PGF2alpha and 24 h later with a second GnRH, n=16. Oestrus-mating detection was carried out at 4 h intervals starting on day 0 [the day of CIDR withdrawal (CIDR-eCG group), the day of second PGF2alpha treatment (PGF2alpha-PGF2alpha group) and the day of PGF2alpha treatment (GnRH-PGF2alpha-GnRH group)]. Ovarian dynamics was monitored by ultrasound every 12 h beginning on day 0 and continued for 4 days. Blood samples were obtained daily for progesterone (P4) and oestradiol 17beta (E2) estimation starting on day 0 and continued for 4 days. The obtained results showed that, oestrus expression, ovulation and conception were greater (p<0.05) in CIDR-eCG and PGF2alpha-PGF2alpha groups than in GnRH-PGF2alpha-GnRH group. All ewes of PGF2alpha-PGF2alpha group presented, on day of second PGF2alpha injection with mature CL (P4>2.0 ng/ml), compared to 42.9% in GnRH-PGF2alpha-GnRH group (p=0.01). The peak of oestrus occurred 32-52, 48-60 and 28-96 h after the end of treatment in CIDR-eCG, PGF2alpha-PGF2alpha and GnRH-PGF2alpha-GnRH groups, respectively. Ovulation started 48 h after treatment in all groups and extended for 24, 36 and 48 h for CIDR-eCG, PGF2alpha-PGF2alpha and GnRH-PGF2alpha-GnRH groups, respectively. Results demonstrated that oestrus and ovulation synchronization could be efficiently achieved in Farafra ewes using either CIDR-eCG or PGF2alpha-PGF2alpha regimes; however, the GnRH-PGF2alpha-GnRH treatment induced a more spread oestrus and ovulation that may make the protocol inadequate for timed artificial insemination.

Transport characteristics of mammalian Rh and Rh glycoproteins expressed in heterologous systems.

PubMed

Westhoff, C M; Wylie, D E

2006-01-01

The development and use of heterologous expression systems is critical for deciphering the function of mammalian Rh and Rh-glycoproteins. The studies here use Xenopus oocytes, well known for their ability to readily traffic and express difficult membrane proteins, and S. cerevisiae wild-type strains and mutants that are defective in ammonium transport. Data obtained in both of these expression systems revealed that mammalian Rh-glycoprotein-mediated transport (RhAG, RhBG, and RhCG) is an electroneutral process that is driven by the NH4+ concentration and the transmembrane H+ gradient, effectively exchanging NH4+ for H+ in a process that results in transport of net NH3. Homology modeling and functional studies suggest that the more recently evolved erythrocyte blood group proteins, RhCE and RhD, may not function directly in ammonia transport and may be evolving a new function in the RBC membrane. The relationship of Rh and Rh-glycoproteins to the Amt/Mep ammonium transporters is substantiated with functional transport data and structural modeling.

Delayed administration of recombinant human parathyroid hormone improves early biomechanical strength in a rat rotator cuff repair model.

PubMed

Duchman, Kyle R; Goetz, Jessica E; Uribe, Bastian U; Amendola, Andrew M; Barber, Joshua A; Malandra, Allison E; Fredericks, Douglas C; Hettrich, Carolyn M

2016-08-01

Despite advances in intraoperative techniques, rotator cuff repairs frequently do not heal. Recombinant human parathyroid hormone (rhPTH) has been shown to improve healing at the tendon-to-bone interface in an established acute rat rotator cuff repair model. We hypothesized that administration of rhPTH beginning on postoperative day 7 would result in improved early load to failure after acute rotator cuff repair in an established rat model. Acute rotator cuff repairs were performed in 108 male Sprague-Dawley rats. Fifty-four rats received daily injections of rhPTH beginning on postoperative day 7 until euthanasia or a maximum of 12 weeks postoperatively. The remaining 54 rats received no injections and served as the control group. Animals were euthanized at 2 and 16 weeks postoperatively and evaluated by gross inspection, biomechanical testing, and histologic analysis. At 2 weeks postoperatively, rats treated with rhPTH demonstrated significantly higher load to failure than controls (10.9 vs. 5.2 N; P = .003). No difference in load to failure was found between the 2 groups at 16 weeks postoperatively, although control repairs more frequently failed at the tendon-to-bone interface (45.5% vs. 22.7%; P = .111). Blood vessel density appeared equivalent between the 2 groups at both time points, but increased intracellular and extracellular vascular endothelial growth factor expression was noted in the rhPTH-treated group at 2 weeks. Delayed daily administration of rhPTH resulted in increased early load to failure and equivalent blood vessel density in an acute rotator cuff repair model. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Unexpected suppression of anti-Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin.

PubMed

Branch, Donald R; Scofield, Terry L; Moulds, John J; Swanson, Jane L

2011-04-01

Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti-D in D- mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG-induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316-22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β-1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ-1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis. Red blood cells and serum were analyzed using saline-tube indirect antiglobulin test methods. RhIG (RhoGAM) was administered after each amniocentesis performed at 28, 31, and 36 weeks' gestation. A group A, D-(cde), K+, Fy(a-b+), MNs, Jk(a+b+) mother with no detectable anti-D had an anti-Fy(a) titer of 4096 before RhIG but only 256 after RhIG. Mother gave birth to a group O, D-(cde), Fy(a+b+) healthy baby boy having a weak-positive direct antiglobulin test with anti-Fy(a) eluted from his cells and the titer in the cord serum was 4. This case demonstrates the potential immunosuppressive properties of RhIG for down regulation of a possible clinically significant alloantibody, not anti-D, where no D+ antigen is in the circulation of the mother. The case illustrates the potential utility for using RhIG to modulate antibody levels in situations other than for classical suppression of anti-D production. Although the mechanism in this case is unknown, TGFβ-1-mediated or antibody-mediated immunosuppression to soluble nonparticulate antigens are possible mechanisms. © 2010 American Association of Blood Banks.

Validation of paper-based assay for rapid blood typing.

PubMed

Al-Tamimi, Mohammad; Shen, Wei; Zeineddine, Rania; Tran, Huy; Garnier, Gil

2012-02-07

We developed and validated a new paper-based assay for the detection of human blood type. Our method involves spotting a 3 μL blood sample on a paper surface where grouping antibodies have already been introduced. A thin film chromatograph tank was used to chromatographically elute the blood spot with 0.9% NaCl buffer for 10 min by capillary absorption. Agglutinated red blood cells (RBCs) were fixed on the paper substrate, resulting in a high optical density of the spot, with no visual trace in the buffer wicking path. Conversely, nonagglutinated RBCs could easily be eluted by the buffer and had low optical density of the spot and clearly visible trace of RBCs in the buffer wicking path. Different paper substrates had comparable ability to fix agglutinated blood, while a more porous substrate like Kleenex paper had enhanced ability to elute nonagglutinated blood. Using optimized conditions, a rapid assay for detection of blood groups was developed by spotting blood to antibodies absorbed to paper and eluted with 200 μL of 0.9% NaCl buffer directly by pipetting. RBCs fixation on paper accurately detected blood groups (ABO and RhD) using ascending buffer for 10 min or using a rapid elution step in 100/100 blood samples including 4 weak AB and 4 weak RhD samples. The assay has excellent reproducibility where the same blood group was obtained in 26 samples assessed in 2 different days. Agglutinated blood fixation on porous paper substrate provides a new, simple, and sensitive assay for rapid detection of blood group for point-of-care applications. © 2011 American Chemical Society

Varied distribution of RhD epitopes in the Indian population.

PubMed

Kulkarni, S S; Gupte, S C; Vasantha, K; Mohanty, D; Ghosh, K

2007-01-01

Inhabited by more than 4000 caste and tribal groups, India has an extremely heterogenous population. For thousands of years many tribal groups have practised endogamy and are practically genetically isolated. Traditionally, polyclonal anti-D reagent has been used for RhD typing; though monoclonal antibodies are increasingly being used. As a result, blood banks find it difficult to assign the RhD status to an increasing number of people. As monoclonal anti-D typing reagents may not detect all RhD antigen epitopes, we studied the RhD antigen epitope heterogeneity in different population groups in India. Red cells of 5315 RhD-positive individuals belonging to different castes and tribes of India were tested with 30 different epitope-specific monoclonal anti-D antibodies. No single monoclonal antibody could detect all RhD-positive red cells detected by polyclonal antisera. The highest proportion of D antigen was detected by LHM 76/55 and BRAD-8 (98%) monoclonal antibodies. We need to determine the correct mix of monoclonal antibodies that will detect nearly all RhD antigens detected by polyclonal anti-D sera. Similarly, before accepting monoclonal anti-D for therapeutic use, it would be necessary to determine the appropriate ones for use in the Indian population.

Red cell antigen prevalence predicted by molecular testing in ethnic groups of South Texas blood donors.

PubMed

Aranda, Lorena I; Smith, Linda A; Jones, Scott; Beddard, Rachel

2015-01-01

Alloimmunization to red blood cell antigens is seen in patients receiving chronic blood transfusion. Knowing the prevalence of blood group antigens of the different ethnicities of South Texas donors can provide better management of rare blood inventory for patients in this geographical area. A total of 4369 blood donors were tested and analyzed for various antigens in the following blood group systems: ABO, Rh, Kell, Duffy, Kidd, MNS, Lutheran, Dombrock, Landsteiner-Wiener, Diego, Colton, and Scianna. Donors tested to be group 0 or A were serologically tested for the Rh (C, E, c, e) antigens. Those that tested as presumably R1R1, R2R2, or Ror were then genotyped. Donors constituted three major ethnicities: black (18.3%), Hispanic (36.3%), and Caucasian (41.1%); ethnicities comprised of Asian, American Indian, multiracial, and other accounted for the remaining donors (4.3%). The most likely common Rh phenotype for each ethnicity is as follows: black -Ror (44.4%), Hispanic -R1R1 (59.0%), and Caucasian -R1R1 (38.9%). The prevalence of Kell, Duffy, and Kidd blood group system antigens in black and Caucasian donors is comparable with published reports for the entire U.S. The black South Texas donor population had an 8.8 percent increase in prevalence of the Fy(a+b-) phenotype as compared with these published reports; the Hispanic South Texas donor population had a prevalence of 36.1 percent of the Fy(a+b-) phenotype. Regarding the Diego blood group system, the Hispanic donor population in South Texas had a prevalence of 93.5 percent for the Di(a-b+) phenotype as compared with published reports for the entire U.S. (>99.9%). The Hispanic population had a prevalence of 7.9 percent of donors testing as M-N+S-s+ as compared with 20.2 percent and 15.6 percent for black and Caucasian donors, respectively. This study helped us determine the prevalence of each of the blood group antigens in the South Texas donor population to establish and maintain adequate rare inventory of each. Molecular red blood cell genotyping allows transfusion services to increase their availability of rare phenotypes for chronically transfused patients.

Confidential unit exclusion at the regional blood bank in Montes Claros - Fundação Hemominas

PubMed Central

Maia, Caroline Nogueira; Ruas, Munic de Oliveira; Urias, Elaine Veloso Rocha

2012-01-01

Objective This study aimed at analyzing the rate of self-exclusion at the Regional Blood Bank in Montes Claros. Methods Data of self-excluding donors from August 2008 to August 2010 were analyzed. The following variables were considered: age, marital status, gender, ethnical background, blood group, Rh factor, number of donations, type of donation and serologic results. Results During the analyzed period, 34,778 individuals donated blood, 215 (0.62%) of which were self-excluded; 12% of donors did not answer, 6.3% ballots were spoilt and 13.6% of the responses were considered non-compliant. The profile of the donors was: male (81.9%), single (50.7%), aged between 19 and 29 years old (52.1%), Mulatto (48.3%), blood group O (32.1%) and positive Rh (32.1%). Most individuals were donating for the 2ndto 5th time (43.7%) and had negative serology (94.4%). Conclusion It was not evident that self-excluding donors had higher rates of seropositivity. PMID:23049378

Is there a relationship between genetic factors and the incidence and severity of H1N1 in Kosova?: A preliminary investigation and pointers for further research.

PubMed

Dreshaj, Shemsedin; Alija, Avdulla J; Schlagenhauf, Patricia; Doda, Teuta; Geca, Njomeza; Bajraktari, Ismet; Bresgen, Nikolaus; Eckl, Peter M

Host genetic factors may impact susceptibility to infection. A small number of studies have investigated the association between factors such as ABO blood groups and selected phenotypes on the incidence and severity of H1N1 infections with inconclusive results. Using data from the Clinic of Infectious Diseases - University Clinical Centre Prishtina and based on the examination of 125 patients hospitalized with H1N1 in the period 2009-2014, the frequency of blood groups from ABO and Rhesus (Rh) systems as phenotypical markers were evaluated. In addition, other phenotypes such as ear lobe free/ear lobe attached, normal chin/cleft chin, tongue roller/non roller, hand clasping right thumb over/hand clasping left thumb over, right-handed/left-handed, dark eyes/light eyes were also analyzed. The data obtained from the 125 hospitalized patients were compared with the data from the Kosovar population (n = 2000) as a reference group. A total of 303 patients with H1N1 were hospitalized in the period 2009-2015. Blood group and phenotype data available from 125 hospitalized H1N1 patients showed significant differences in the frequencies of the blood groups from Rh system as well as in two (out of six) phenotypes of the selected morphological traits compared to reference groups. The findings from this preliminary study indicate that these Rh system and phenotype differences may be linked to H1N1 susceptibility and may guide identification of risk groups and populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

ABO blood groups, Rhesus factor, and anaphylactic reactions due to Hymenoptera stings.

PubMed

Pałgan, Krzysztof; Bartuzi, Zbigniew; Chrzaniecka, Elżbieta

2017-09-21

Numerous publications indicate that the prevalence of some infectious, neoplastic and immunological diseases are associated with ABO blood groups. The aim of this study was to verify whether ABO and Rh blood groups are associated with severe anaphylactic reactions after Hymenoptera stings. A study was undertaken of 71,441 Caucasian subjects living in the same geographic area. The study group included 353 patients with diagnosed systemic anaphylaxis to Hymenoptera venom. Control group included 71,088 healthy blood donors. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses. No statistically significant interactions were observed between the ABO blood group and anaphylactic reactions to Hymenoptera.

Red Blood Cell Antigen Genotyping for Sickle Cell Disease, Thalassemia, and Other Transfusion Complications.

PubMed

Fasano, Ross M; Chou, Stella T

2016-10-01

Since the discovery of the ABO blood group in the early 20th century, more than 300 blood group antigens have been categorized among 35 blood group systems. The molecular basis for most blood group antigens has been determined and demonstrates tremendous genetic diversity, particularly in the ABO and Rh systems. Several blood group genotyping assays have been developed, and 1 platform has been approved by the Food and Drug Administration as a "test of record," such that no phenotype confirmation with antisera is required. DNA-based red blood cell (RBC) phenotyping can overcome certain limitations of hemagglutination assays and is beneficial in many transfusion settings. Genotyping can be used to determine RBC antigen phenotypes in patients recently transfused or with interfering allo- or autoantibodies, to resolve discrepant serologic typing, and/or when typing antisera are not readily available. Molecular RBC antigen typing can facilitate complex antibody evaluations and guide RBC selection for patients with sickle cell disease (SCD), thalassemia, and autoimmune hemolytic anemia. High-resolution RH genotyping can identify variant RHD and RHCE in patients with SCD, which have been associated with alloimmunization. In the future, broader access to cost-efficient, high-resolution RBC genotyping technology for both patient and donor populations may be transformative for the field of transfusion medicine. Copyright © 2016. Published by Elsevier Inc.

Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients

PubMed Central

Dhawan, Hari Krishan; Kumawat, Vijay; Marwaha, Neelam; Sharma, Ratti Ram; Sachdev, Suchet; Bansal, Deepak; Marwaha, Ram Kumar; Arora, Satyam

2014-01-01

Background: The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. Materials and Methods: The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards. Results: Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-Cw = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Conclusion: Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization. PMID:25161344

Paper-based device for rapid typing of secondary human blood groups.

PubMed

Li, Miaosi; Then, Whui Lyn; Li, Lizi; Shen, Wei

2014-01-01

We report the use of bioactive paper for typing of secondary human blood groups. Our recent work on using bioactive paper for human blood typing has led to the discovery of a new method for identifying haemagglutination of red blood cells. The primary human blood groups, i.e., ABO and RhD groups, have been successfully typed with this method. Clinically, however, many secondary blood groups can also cause fatal blood transfusion accidents, despite the fact that the haemagglutination reactions of secondary blood groups are generally weaker than those of the primary blood groups. We describe the design of a user-friendly sensor for rapid typing of secondary blood groups using bioactive paper. We also present mechanistic insights into interactions between secondary blood group antibodies and red blood cells obtained using confocal microscopy. Haemagglutination patterns under different conditions are revealed for optimization of the assay conditions.

Risk factors for refeeding hypophosphatemia in Japanese inpatients with anorexia nervosa.

PubMed

Kameoka, Naomi; Iga, Jun-ichi; Tamaru, Mai; Tominaga, Takeo; Kubo, Hiroko; Watanabe, Shin-Ya; Sumitani, Satsuki; Tomotake, Masahito; Ohmori, Tetsuro

2016-04-01

Refeeding in patients with anorexia nervosa (AN) is associated with a risk of refeeding syndrome, which is a disruption in metabolism with a variety of features including hypophosphatemia. We evaluated the risk factors for refeeding hypophosphatemia (RH) during nutritional replenishment in Japanese patients with AN. We retrospectively examined clinical data for 99 female inpatients (mean age 30.9 ± 10.7 years; range, 9 - 56 years). RH (phosphate < 2.3 mg/dL) occurred within 4.8 ± 3.7 days of hospital admission and was still observed at 28 days after admission in 21 of the 99 cases (21.2%). Oral or intravenous phosphate was given to some patients to treat or prevent RH. Patients with RH had a significantly lower body mass index, were older, and had higher blood urea nitrogen than those without RH. Severe complications associated with RH were recorded in only one patient who showed convulsions and disturbed consciousness at Day 3 when her serum phosphate level was 1.6 mg/dL. The significant risk factors for RH that we identified were lower body mass index, older age, and higher blood urea nitrogen at admission. No significant difference in total energy intake was seen between the RH and no RH groups, suggesting that RH may not be entirely correlated with energy intake. Precisely predicting and preventing RH is difficult, even in patients with AN who are given phosphate for prophylaxis. Thus, serum phosphate levels should be monitored for more than 5 days after admission. © 2015 Wiley Periodicals, Inc.

Blood Group Antibodies in Obstetrics

PubMed Central

Neurath, Doris; Nimrod, Carl

1991-01-01

A retrospective survey of the frequency, nature, and effect of blood group antibodies on obstetrical outcome was conducted over 4 years in a large community hospital. A total of 189 antibodies were identified in 165 patients. Twenty clinically significant outcomes occurred, including three stillbirths. All clinically significant cases of hemolytic disease of the newborn were caused by Rh antibodies. PMID:21229104

Recombinant human (rh) stem cell factor and rhIL-4 stimulate differentiation and proliferation of CD3+ cells from umbilical cord blood and CD3+ cells enhance FcepsilonR1 expression on fetal liver-derived mast cells in the presence of rhIL-4.

PubMed

Lee, Eunkyung; Min, Hae-Ki; Oskeritzian, Carole A; Kambe, Naotomo; Schwartz, Lawrence B; Wook Chang, Hyeun

2003-11-01

We previously reported that rhIL-4 induced apoptosis and rhIL-6 mediated protection of human mast cells derived from cord blood mononuclear cells. Based on the result, we attempted to obtain the phenotypes and differentiation of CD3+ cells from cord blood by investigating their cell surface markers in the presence of rhSCF plus rhIL-4. The effect of co-cultured CD3+ cells on fetal liver mast cells (FLMCs) was also determined. Phenotypes from cord blood-derived cells were analyzed by flow cytometry and cell numbers were determined. Fetal liver mast cells were cultured with cord blood-derived cells (mainly CD3+) in the presence of rhSCF and/or rhIL-4 and were analyzed to determine cell number and expression of Kit+ and FcepsilonR1. The percentage of CD3+ cells from cord blood-derived cells on day 0 was about 41 +/- 13.5%, following monocytes and granulocytes. CD3+ cells increased in number (1.5-fold) and purity (90%), whereas other cell types did not survive. More than 60% of CD3+ cells from cord blood at day 0 were CD4(-)CD8-. These double-negative cells dramatically decreased by 1 week of culture, while CD4+CD8+ cells increased in number and purity through 3 weeks of culture, and then decreased as greater numbers of single-positive T cells emerged. We also found that FcepsilonR expression on FLMC increased in the presence of rhIL-4, but was not affected by the T cells that developed from cord blood mononuclear cells. The results indicate that IL-4, a Th2 type cytokine, together with rhSCF, can induce T cell proliferations, differentiation, and maturation from cord blood progenitor cells.

ABO/Rh Blood-Typing Model: A Problem-Solving Activity

ERIC Educational Resources Information Center

Wake, Carol

2005-01-01

An ARO/Rh Blood-Typing kit useful for students to visualize blood-typing activities and practice problem-solving skills with transfusion reactions is presented. The model also enables students to identify relationships between A, B, and Rh antigens and antibodies in blood and to understand molecular mechanisms involved in transfusion agglutination…

Continuous Positive Airway Pressure Reduces Night-Time Blood Pressure and Heart Rate in Patients With Obstructive Sleep Apnea and Resistant Hypertension: The RHOOSAS Randomized Controlled Trial.

PubMed

Joyeux-Faure, Marie; Baguet, Jean-Philippe; Barone-Rochette, Gilles; Faure, Patrice; Sosner, Philippe; Mounier-Vehier, Claire; Lévy, Patrick; Tamisier, Renaud; Pépin, Jean-Louis

2018-01-01

Most patients with resistant hypertension (RH) have obstructive sleep apnea (OSA). We aimed to determine the impact of OSA and continuous positive airway pressure (CPAP) treatment on the leptin profile and blood pressure (BP) in patients with RH. After an initial case-control study (RH with and without OSA), we performed a randomized, single blind study in OSA + RH patients receiving either sham CPAP (3 months) followed by active CPAP (6 months) or 6 months of active CPAP. The primary outcome was the comparison of leptin levels between groups of RH patients with or without OSA. Secondary outcomes were the comparison of metabolic parameters, biomarkers of sympathetic activity, and BP indices between the two groups of RH patients with or without OSA. The same outcomes were then evaluated and compared before and after sham and effective CPAP intervention. Sixty-two patients (60 ± 10 years; 77% men) with RH (24-h daytime systolic BP (SBP)/diastolic BP: 145 ± 13/85 ± 10 mmHg, 3.7 antihypertensive drugs) were included. The 37 RH patients exhibiting OSA (60%) were predominantly men (87 vs 64% for non-OSA patients), with a greater prevalence of metabolic syndrome and higher creatininemia. Their leptin concentrations were significantly lower than in non-OSA patients [9 (6; 15) vs 17 (6; 29) ng/mL] but increased after 6 months of CPAP. Three months of effective CPAP significantly decreased night-time SBP by 6.4 mmHg and heart rate (HR) by 6.0 bpm, compared to sham CPAP. The association between OSA and RH corresponds to a specific, predominately male phenotype with a higher burden of metabolic syndrome and higher creatininemia but there was no significant difference between OSA and non-OSA patients regarding BP indices, and the number of antihypertensive drugs used. Active CPAP could be efficient at decreasing night-time BP and HR, but there was no difference between CPAP and sham CPAP groups for all metabolic and SNS markers (NCT00746902 RHOOSAS).

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities.

PubMed

Coleman, Thomas R; Westenfelder, Christof; Tögel, Florian E; Yang, Ying; Hu, Zhuma; Swenson, Leanne; Leuvenink, Henri G D; Ploeg, Rutger J; d'Uscio, Livius V; Katusic, Zvonimir S; Ghezzi, Pietro; Zanetti, Adriana; Kaushansky, Kenneth; Fox, Norma E; Cerami, Anthony; Brines, Michael

2006-04-11

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose-dependent risk of adverse effects has been associated with rhEPO administration, especially in high-risk groups, including polycythemia-hyperviscosity syndrome, hypertension, and vascular thrombosis. Of note, several clinical trials employing relatively high dosages of rhEPO in oncology patients were recently halted after an increase in mortality and morbidity, primarily because of thrombotic events. We recently identified a heteromeric EPO receptor complex that mediates tissue protection and is distinct from the homodimeric receptor responsible for the support of erythropoiesis. Moreover, we developed receptor-selective ligands that provide tools to assess which receptor isoform mediates which biological consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in the rat increases systemic blood pressure, reduces regional renal blood flow, and increases platelet counts and procoagulant activities. In contrast, carbamylated rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective, increases renal blood flow, promotes sodium excretion, reduces injury-induced elevation in procoagulant activity, and does not effect platelet production. These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection.

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities

PubMed Central

Coleman, Thomas R.; Westenfelder, Christof; Tögel, Florian E.; Yang, Ying; Hu, Zhuma; Swenson, LeAnne; Leuvenink, Henri G. D.; Ploeg, Rutger J.; d’Uscio, Livius V.; Katusic, Zvonimir S.; Ghezzi, Pietro; Zanetti, Adriana; Kaushansky, Kenneth; Fox, Norma E.; Cerami, Anthony; Brines, Michael

2006-01-01

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose-dependent risk of adverse effects has been associated with rhEPO administration, especially in high-risk groups, including polycythemia–hyperviscosity syndrome, hypertension, and vascular thrombosis. Of note, several clinical trials employing relatively high dosages of rhEPO in oncology patients were recently halted after an increase in mortality and morbidity, primarily because of thrombotic events. We recently identified a heteromeric EPO receptor complex that mediates tissue protection and is distinct from the homodimeric receptor responsible for the support of erythropoiesis. Moreover, we developed receptor-selective ligands that provide tools to assess which receptor isoform mediates which biological consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in the rat increases systemic blood pressure, reduces regional renal blood flow, and increases platelet counts and procoagulant activities. In contrast, carbamylated rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective, increases renal blood flow, promotes sodium excretion, reduces injury-induced elevation in procoagulant activity, and does not effect platelet production. These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection. PMID:16585502

Stability of user-friendly blood typing kits stored under typical military field conditions.

PubMed

Bienek, Diane R; Chang, Cheow K; Charlton, David G

2009-10-01

To help preserve in-theater strength within deployed military units, commercially available, rapid, user-friendly ABO-Rh blood typing kits were evaluated to determine their stability in storage conditions commonly encountered by the warfighter. Methods for environmental exposure testing were based on MIL-STD-810F. When Eldon Home Kits 2511 were exposed to various temperature/relative humidity conditions, the results were comparable to those obtained with the control group and those obtained with industry-standard methods. For the ABO-Rh Combination Blood Typing Experiment Kits, 2 of the exposure treatments rendered them unusable. In addition, a third set of exposure treatments adversely affected the kits, resulting in approximately 30% blood type misclassifications. Collectively, this evaluation of commercial blood typing kits revealed that diagnostic performance can vary between products, lots, and environmental storage conditions.

Profile of Rh, Kell, Duffy, Kidd, and Diego blood group systems among blood donors in the Southwest region of the Paraná state, Southern Brazil.

PubMed

Zacarias, Joana Maira Valentini; Langer, Ieda Bernadete Volkweis; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

2016-12-01

The aim of this study was to assess the distribution of alleles and genotypes of the blood group systems Rh, Kell, Duffy, Kidd, and Diego in 251 regular blood donors registered in the hemotherapy unit of the Southwestern region of Paraná, Southern Brazil. The frequencies were obtained by direct counting on a spreadsheet program and statistical analyses were conducted in order to compare them with other Brazilian populations using chi-squared with Yates correction on OpenEpi software. The frequencies of RHD* negative, RHCE*c/c and RHCE*e/e were higher than expected for the Caucasian population. A difference was also observed for FY alleles, FY*01/FY*01 genotype and FY*02N.01 -67T/C (GATA Box mutation). Two homozygous individuals were defined as a low frequency phenotype K + k- (KEL*01.01/KEL*01.01) and, for Diego blood group system the rare DI*01 allele was found in ten blood donors, of which one was DI*01/DI* 01 (0.4%). The allele and genotype frequencies of Kidd blood group system were similar to expected to Caucasians. The results showed the direction in which to choose donors, the importance of extended genotyping in adequate blood screening and the existence of rare genotypes in Brazilian regular blood donors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systemic and splanchnic metabolic response to exogenous human growth hormone.

PubMed

Dahn, M S; Lange, M P

1998-05-01

Evidence exists indicating that growth hormone (GH) resistance in some disease states such as hypercatabolic conditions may limit the metabolic benefit associated with recombinant human growth hormone (rhGH) administration. It was the purpose of this study to compare the systemic and splanchnic effects of rhGH in patients with sepsis exhibiting systemic inflammatory response syndrome (SIRS) with the response observed in normal volunteers. Because insulin-like growth factor I (IGF-I) is believed to be the dominant factor responsible for the anabolic effects of rhGH, particular attention was given to this secondary effector. The systemic and splanchnic effects of rhGH (0.15 mg/kg/day) were studied in normal volunteers (n = 5), critically ill patients with sepsis exhibiting SIRS (n = 6), and patients with sepsis exhibiting SIRS while receiving total parenteral nutrition (n = 6). Basal and end study IGF-I, urinary urea excretion, hepatic blood flow, hepatic venous oxygen content, and splanchnic oxygen exchange were measured after a 48-hour course of rhGH. Fasting basal IGF-I concentrations were reduced by 75% to 83% in patients with sepsis/SIRS relative to normal control subjects. After 48 hours of rhGH, peak IGF-I concentrations were 74% and 76% lower in patients in the Sepsis/SIRS and Sepsis/SIRS + Nutrition groups, respectively, compared with normal control subjects. Despite the attenuated IGF-I rise in patients, urea excretion declined by a similar magnitude in all three groups. Hepatic blood flow remained unaffected, but rhGH administration increased splanchnic oxygen consumption in all groups (control, +57%*; Sepsis/SIRS, +13%; Sepsis/SIRS + Nutr +42%*; *p < 0.05 relative to corresponding basal) resulting in a decline of basal to end therapy hepatic venous oxygen saturation (control, 67 +/- 4% to 62 +/- 11%; Sepsis/SIRS, 51% +/- 14% to 43% +/- 14%*; Sepsis/SIRS + Nutr, 62% +/- 11% to 55% +/- 16%; *p < 0.05 relative to corresponding control value), suggesting that rhGH may induce centrilobular hepatic hypoxia, which may contribute to the diminished IGF-I response. Although critically ill patients exhibit an IGF-I increase in response to exogenous rhGH, the rise is markedly attenuated compared with healthy volunteers, indicating the presence of GH resistance. Unexpectedly, the changes in the anabolic hormone IGF-I did not appear to be related to the reduction in urea excretion. This may provide some additional evidence for IGF-I resistance. Finally, rhGH is associated with an augmented splanchnic oxygen consumption but no corresponding increase in regional blood flow. As a result, regional tissue hypoxia may arise and contribute to the impaired or suboptimal IGF-I response pattern.

High-versus standard-dose filgrastim (rhG-CSF) for mobilization of peripheral-blood progenitor cells from allogeneic donors and CD34(+) immunoselection.

PubMed

Engelhardt, M; Bertz, H; Afting, M; Waller, C F; Finke, J

1999-07-01

The efficacy of a high- versus a standard-dose filgrastim (recombinant human granulocyte colony-stimulating factor, or rhG-CSF) regimen to mobilize peripheral-blood progenitor cells (PBPCs) for allogeneic transplantation was investigated in 75 healthy donors. From December 1994 to December 1997, 75 consecutive donors (median age, 38 years; range, 17 to 67 years) were assigned to two different schedules of rhG-CSF for PBPC mobilization. Fifty donors received 24 microg rhG-CSF/kg body weight (BW) divided into two daily subcutaneous injections (two doses of 12 microg, group A), whereas 25 were treated with 10 microg rhG-CSF once daily (group B). Apheresis was started on day 4 in group A and on day 5 in group B. Target CD34(+) cell numbers in apheresis products were >/= 4 x 10(6)/kg recipient BW. Cytokine priming and collection of PBPCs were equally well tolerated in both groups. Significantly higher CD34(+) cell numbers in group A with 3. 7 x 10(6)/kg recipient BW/apheresis (0.47 x 10(6)/L apheresis) compared with 2 x 10(6)/kg recipient BW/apheresis (0.25 x 10(6)/L apharesis) in group B were obtained (P <.05). Using standard aphereses (median, 9 L), two doses of 12 microg rhG-CSF/kg allowed collection of >/= 4 x 10(6)/kg CD34(+) cells with two aphereses (range, one to three) in group A versus three aphereses (range, one to six) in group B (P <.015). Donor age, sex, and BW influenced the collection of CD34(+) cell numbers: in particular, significantly higher apheresis results were obtained in donors younger than 40 years compared with donors older than 40 years of age (P <.05). In 65 CD34(+) selection procedures using avidin-biotin immunoabsorption columns (Ceprate SC System, CellPro, Bothell, WA), a median CD34(+) purity of 53%, CD34(+) recovery of 40%, and the collection of 2 x 10(6)/kg CD34(+) cells/selection were achieved. In group A with higher CD34(+) cells/kg/apheresis, CD34(+) purity, recovery, and cell yields were 60%, 45%, and 2.3 x 10(6)/kg/selection, respectively, as compared with 48%, 31%, and 0.7 x 10(6)/kg in group B (P <.05). Our results demonstrate that twice daily rhG-CSF (two doses of 12 microg/kg BM) compared with once daily rhG-CSF (10 microg/kg BW), in addition to being well tolerated, significantly improves PBPC mobilization, allows the collection of higher numbers of CD34(+) cells with one or two standard aphereses, and facilitates subsequent selection procedures in healthy allogeneic donors.

Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe

PubMed Central

Batailler, Martine; Caraty, Alain; Malpaux, Benoît; Tillet, Yves

2004-01-01

Background During the preovulatory surge of gonadotropin-releasing hormone (GnRH), a very large amount of the peptide is released in the hypothalamo-hypophyseal portal blood for 24-36H00. To study whether this release is linked to a modification of the morphological organization of the GnRH-containing neurons, i.e. morphological plasticity, we conducted experiments in intact ewes at 4 different times of the oestrous cycle (before the expected LH surge, during the LH surge, and on day 8 and day 15 of the subsequent luteal phase). The cycle stage was verified by determination of progesterone and LH concentrations in the peripheral blood samples collected prior to euthanasia. Results The distribution of GnRH-containing neurons throughout the preoptic area around the vascular organ of the lamina terminalis was studied following visualisation using immunohistochemistry. No difference was observed in the staining intensity for GnRH between the different groups. Clusters of GnRH-containing neurons (defined as 2 or more neurons being observed in close contact) were more numerous during the late follicular phase (43 ± 7) than during the luteal phase (25 ± 6), and the percentage of clusters was higher during the beginning of the follicular phase than during the luteal phase. There was no difference in the number of labelled neurons in each group. Conclusions These results indicate that the morphological organization of the GnRH-containing neurons in ewes is modified during the follicular phase. This transitory re-organization may contribute to the putative synchronization of these neurons during the surge. The molecular signal inducing this plasticity has not yet been identified, but oestradiol might play an important role, since in sheep it is the only signal which initiates the GnRH preovulatory surge. PMID:15555074

[Identification of alloantibodies and their associations: Balance sheet of 3 years at the Regional Center of Blood Transfusion in Rabat/Morocco and difficult in transfusion management].

PubMed

Achargui, S; Zidouh, A; Abirou, S; Merhfour, F Z; Monsif, S; Amahrouch, S; El Ghobre, A; El Halhali, M; Temmara, H; El Hryfy, A; Motqi, M; Satty, A; Kandili, M; Aghri, M; Hajjout, K; Benajiba, M

2017-11-01

Red blood cell immunization can lead to delays or even an impasse in a transfusion. Determine the specificities of the most common of alloantibodies and their associations to correct management of red blood cell transfused. A retrospective study between 2013 and 2015 in immunohematology laboratories at the Blood Transfusion Center of Rabat in Morocco. The following data were studied: frequency, specificities of alloantibodies, blood group involved in alloimmunization and difficult of management of transfusion in case with association of alloantibodies. Five hundred of alloantibodies were identified in 425 people (372 patients/pregnant women and 53 blood donors). The alloantibodies were directed against the following antigen: RH1 (50.8 %), RH3 (11.4 %), KEL 1 (8.2 %), RH2 (7.6 %), RH4 (4.6 %), MNS1 (4 %), MNS3 (2.6 %), Jka (2.4 %) and Fya (2.2 %). Only one alloantibody was identified in 85 % of cases. In 15 %, at least, two alloantibodies were found. The most common associations were directed against: anti-(D+C) (25), anti-(E+K) (4), anti-(E+c) (3) and anti-(D+C+E) (3). The rhesus system is the most involved in alloimmunization. Frequency of specific associations of alloantibodies was identified: Fya-/Jkb- (18.23 %), Fyb-/Jkb- (11.7 %), Jka-/S- (8.70 %), Jka-/Fyb- (5.20 %), Fyb-/s- (3.40 %) and Fyb-/Jkb-/s- (0.85 %). Red blood cell immunization is a serious problem in transfused patients. This study proves the data of literature, the interest of using RH-Kel1 red cell units compatibles among women in age to procreate and for the transfused patients to reduce the rate of immunization. Associations of antibodies with low frequency suggest a promotion of donation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility.

PubMed

Awad, Hisham A E; Tantawy, Azza A G; El-Farrash, Rania A; Ismail, Eman A; Youssif, Noha M

2014-04-01

ABO antigens are expressed on the surfaces of red blood cells and the vascular endothelium. We studied circulating endothelial microparticles (EMP) in ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial activation to test a hypothesis of possible endothelial injury in neonates with ABO HDN, and its relation with the occurrence and severity of haemolysis. Forty-five neonates with ABO HDN were compared with 20 neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy neonates with matched mother and infant blood groups (healthy controls). Laboratory investigations were done for markers of haemolysis and von Willebrand factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after therapy (exchange transfusion and/or phototherapy). vWF Ag and pre-therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy controls, and were significantly higher in babies with ABO HDN than in those with Rh HDN (p<0.05). In ABO HDN, pre-therapy EMP levels were higher in patients with severe hyperbilirubinaemia than in those with mild and moderate disease or those with Rh HDN (p<0.001). Post-therapy EMP levels were lower than pre-therapy levels in both the ABO HDN and Rh HDN groups; however, the decline in EMP levels was particularly evident after exchange transfusion in ABO neonates with severe hyperbilirubinaemia (p<0.001). Multiple regression analysis revealed that the concentrations of haemoglobin, lactate dehydrogenase and indirect bilirubin were independently correlated with pre-therapy EMP levels in ABO HDN. Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury parallel to the IgG-mediated erythrocyte destruction and could serve as a surrogate marker of vascular dysfunction and disease severity in neonates with this condition.

Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs.

PubMed

Huang, C H; Reid, M E; Chen, Y; Coghlan, G; Okubo, Y

1996-01-01

The Rh blood group system of human red cells contains five major antigens D, C/c, and E/e (the latter four designated "non-D") that are specified by eight gene complexes known as Rh haplotypes. In this paper, we report on the mapping of RH locus and identification of a set of SphI RFLPs that are tightly linked with the Rh structural genes. Using exon-specific probes, we have localized the SphI cleavage sites resulting in these DNA markers and derived a comprehensive map for the RH locus. It was found that the SphI fragments encompassing exons 4-7 of the Rh genes occur in four banding patterns or frameworks that correspond to the distribution and segregation of the common Rh haplotypes. This linkage disequilibrium allowed a genotype-phenotype correlation and direct determination of Rh zygosity related to the Rh-positive or Rh-negative status (D/D, D/d, and d/d). Studies on the occurrence of SphI RFLPs in a number of rare Rh variants indicated that Rh phenotypic diversity has taken place on different haplotype backgrounds and has arisen by diverse genetic mechanisms. The molecular definition of Rh haplotypes by SphI RFLP frameworks should provide a useful procedure for genetic counseling and prenatal assessment of Rh alloimmunization.

Establishment and performance assessment of preparation technology of internal quality control products for blood transfusion compatibility testing.

PubMed

Yu, Yang; Ma, Chunya; Feng, Qian; Chen, Xin; Guan, Xiaozhen; Zhang, Xiaojuan; Chen, Linfeng; Lin, Zilin; Pan, Jichun; Zhang, Ting; Luo, Qun; Wang, Deqing

2013-05-01

The aim of this study was to establish and to optimize the preparation technology of whole blood internal quality control (IQC) products for blood transfusion compatibility testing. Several B-type RhD-negative blood samples collected from healthy donors were mixed. Two groups of whole blood IQC products, namely, the preservative solution group (PS group) and the saline group, were prepared. The agglutination intensity of IQC sample red cells and anti-B antibody, IgM anti-A antibody and reverse-typing A cell, IgG anti-D and O-type RhD-positive red cells, as well as free hemoglobin concentration in the supernatant of the two groups were detected. The erythrocytes in both groups were damaged to a certain extent during storage, but no evident (above moderate) hemolysis was observed in the stored sample within 42 days. The red cells remained structurally complete and the reaction activity of IgG anti-D reagent remained generally unchanged (P>0.05). Although the reaction activity oscillation of IgM anti-A reagent was observed, the agglutination intensity varied within an acceptable range of 1+. No difference was observed between the preparation methods of the samples, i.e., between the erythrocyte washed with saline and the one washed with red cell preservative solution (P>0.05). The long shelf life, low variance between tubes and stable antigen-antibody reaction activity of the whole blood IQC products prepared using the proposed method can meet the requirements of blood transfusion compatibility testing.

Glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factor differently modifies actin polymerization in neutrophils.

PubMed

Zucca, A; Brizzi, S; Riccioni, R; Azzarà, A; Ghimenti, M; Carulli, G

2006-01-01

Several neutrophil functions can be modified by rhG-CSF administration. Neutrophil morphology changes in the course of treatment with Filgrastim (nonglycosylated rhG-CSF), along with impairment of chemotaxis. Both morphology and chemotaxis are not affected by treatment with Lenograstim (glycosylated rhG-CSF). Thus, we evaluated actin polymerization in neutrophils induced by treatment with the two forms of rhG-CSF. In fact, actin polymerization is crucial for neutrophil motility. We evaluated twelve healthy subjects undergoing peripheral blood stem cells (PBSC) mobilization for allogeneic transplantation to HLA-identical siblings. Neutrophils were isolated by peripheral venous blood before and after administration of either Filgrastim (six PBSC donors) or Lenograstim (six PBSC donors). Actin polymerization was investigated by a flow cytometric assay, using FITC-phalloidin as a specific probe for F-actin, and two parameters were measured: spontaneous actin polymerization in resting neutrophils; fMLP-stimulated actin polymerization. Results were expressed as relative F-actin content. Fifteen blood donors were studied as a control group. Filgrastim administration induced an increased relative F-actin content in resting neutrophils; however, no further actin polymerization was observed after fMLP stimulation. Neutrophils from subjects treated with Lenograstim showed a normal behaviour in terms of both spontaneous and stimulated actin polymerization. Glycosylated and nonglycosylated rhG-CSF differently affect actin polymerization in newly generated neutrophils. Such effects may explain some previous findings concerning both morphology and chemotactic properties and may be due to different effects of the two forms of rhG-CSF on proteins involved in neutrophil motility regulation.

Effects of a GnRH administration on testosterone profile, libido and semen parameters of dromedary camel bulls.

PubMed

Monaco, Davide; Fatnassi, Meriem; Padalino, Barbara; Aubé, Lydiane; Khorchani, Touhami; Hammadi, Mohamed; Lacalandra, Giovanni Michele

2015-10-01

GnRH treatment has been suggested to increase testosterone levels temporarily and to stimulate libido in stallions, but its use has not fully ascertained in dromedary camels. The aim of this work was to study the effects of administering 100 μg of GnRH on testosterone profile, libido and semen parameters in dromedary camels. The same bulls were used as self-controls and experimental group. Blood samples were collected every 20 min (T0-T12) for 4h, and semen collections were performed over a 2-hour period after T12. GnRH was administered immediately after T0. In GnRH-treated bulls, testosterone levels showed an upward trend, peaking after 140 min, and then slowly decreasing. GnRH administration also led to a decrease in mating time and an increase in spermatozoa concentration. Overall, it seems that administration of 100 μg GnRH might increase testosterone levels temporarily and enhance camel reproduction performance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, C.H.; Reid, M.E.; Chen, Y.

The Rh blood group system of human red cells contains five major antigens D, C/c, and E/e (the latter four designated {open_quotes}non-D{close_quotes}) that are specified by eight gene complexes known as Rh haplotypes. In this paper, we report on the mapping of the RH locus and identification of a set of SphI RFLPs that are tightly linked with the Rh structural genes. Using exon-specific probes, we have localized the SphI cleavage sites resulting in these DNA markers and derived a comprehensive map for the RH locus. It was found that the SphI fragments encompassing exons 4-7 of the Rh genesmore » occur in four banding patterns or frameworks that correspond to the distribution and segregation of the common Rh haplotypes. This linkage disequilibrium allowed a genotype-phenotype correlation and direct determination of Rh zygosity related to the Rh-positive or Rh-negative status (D/D, D/d, and d/d). Studies on the occurrence of SphI RFLPs in a number of rare Rh variants indicated that Rh phenotypic diversity has taken place on different haplotype backgrounds and has arisen by diverse genetic mechanisms. The molecular definition of Rh haplotypes by SphI RFLP frameworks should provide a useful procedure for genetic counseling and prenatal assessment of Rh alloimmunization. 32 refs., 7 figs., 3 tabs.« less

Systematic RH genotyping and variant identification in French donors of African origin

PubMed Central

Kappler-Gratias, Sandrine; Auxerre, Carine; Dubeaux, Isabelle; Beolet, Marylise; Ripaux, Maryline; Le Pennec, Pierre-Yves; Pham, Bach-Nga

2014-01-01

Background RH molecular analysis has enabled the documentation of numerous variants of RHD and RHCE alleles, especially in individuals of African origin. The aim of the present study was to determine the type and frequency of D and/or RhCE variants among blood donors of African origin in France, by performing a systematic RH molecular analysis, in order to evaluate the implications for blood transfusion of patients of African origin. Materials and methods Samples from 316 African blood donors, whose origin was established by their Fy(a−b−) phenotype, were first analysed using the RHD and RHCE BeadChips Kit (BioArray Solutions, Immucor, Warren, NJ, USA). Sequencing was performed when necessary. Results RHD molecular analysis showed that 26.2% of donors had a variant RHD allele. It allowed the prediction of a partial D in 11% of cases. RHCE molecular analysis showed that 14.2% of donors had a variant RHCE allele or RH [RN or (C)ces] haplotype. A rare Rh phenotype associated with the loss of a high-prevalence antigen or partial RhCE antigens were predicted from RHCE molecular analysis in 1 (0.3%) and 17 (5%) cases, respectively. Discussion Systematic RHD and RHCE molecular analysis performed in blood donors of African origin provides transfusion-relevant information for individuals of African origin because of the frequency of variant RH alleles. RH molecular analysis may improve transfusion therapy of patients by allowing better donor and recipient matching, based not only on phenotypically matched red blood cell units, but also on units that are genetically matched with regards to RhCE variants. PMID:23867180

Actin polymerization in neutrophils from donors of peripheral blood stem cells: divergent effects of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factor.

PubMed

Carulli, Giovanni; Mattii, Letizia; Azzarà, Antonio; Brizzi, Stefania; Galimberti, Sara; Zucca, Alessandra; Benedetti, Edoardo; Petrini, Mario

2006-05-01

Neutrophil functions can be modified by Recombinant human G-CSF (rhG-CSF) treatment, with divergent effects on phagocytosis, motility, bactericidal activity, and surface molecule expression. Neutrophil morphology is modified by treatment with filgrastim (the nonglycosylated form of rhG-CSF), while it is not affected by lenograstim (the glycosylated type of rhG-CSF). Little information is available about actin polymerization in neutrophils from subjects treated with the two types of rhG-CSF. In the current paper we evaluated two groups of donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. Ten subjects were treated with filgrastim and 10 with lenograstim to mobilize PBSC; 15 blood donors were evaluated as a control group. Actin polymerization (both spontaneous and fMLP-stimulated) was studied by a flow cytometric assay. A microscopic fluorescent assay was also carried out to evaluate F-actin distribution in neutrophils. We found that filgrastim induced an increased F-actin content in resting neutrophils, along with morphologic evidence for increased actin polymerization distributed principally at the cell membrane and frequently polarized in focal areas; in addition, fMLP was not able to induce further actin polymerization. On the contrary, treatment with lenograstim was associated with F-actin content, distribution, and polymerization kinetics indistinguishable from those displayed by control neutrophils. Such experimental results show that filgrastim and lenograstim display divergent effects also on neutrophil actin polymerization and provide further explanation for previous experimental findings. 2006 Wiley-Liss, Inc.

Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty.

PubMed

Poomthavorn, Preamrudee; Khlairit, Patcharin; Mahachoklertwattana, Pat

2009-01-01

A test involving 100 microg of intravenous gonadotropin-releasing hormone (GnRH) is a gold standard for confirming the diagnosis of central precocious puberty (CPP). However, intravenous GnRH for testing is commercially limited. To develop subcutaneous GnRH agonist (GnRH-A) testing and define a peak luteinizing hormone (LH) cutoff value in diagnosing CPP. A retrospective study of 101 girls with sexual precocity was undertaken. All girls underwent 100 microg subcutaneous GnRH-A (triptorelin) testing. Blood samples before and 30, 60, 90 and 120 min after GnRH-A injection were analyzed for LH and follicle-stimulating hormone levels. Criteria for diagnosing CPP include accelerated height, advanced bone age and pubertal-sized uterus and ovaries. Fifty-five girls were documented as having CPP. The remaining 46 girls were diagnosed with premature thelarche (PT). Peak LH concentration in the CPP group was significantly greater than that of the PT group with a median (range) of 10.0 IU/l (2.93-65.39) and 3.04 IU/l (0.19-8.82), respectively. Peak LH was achieved within 60 min following GnRH-A injection. Peak LH of 6 IU/l provided the most appropriate cutoff level in diagnosing CPP with a sensitivity of 89.1% and a specificity of 91.3%. Subcutaneous GnRH-A can be used as an alternative to confirm the diagnosis of CPP. Copyright 2009 S. Karger AG, Basel.

Basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality.

PubMed

Devkota, Bhuminand; Takahashi, Ken-Ichi; Matsuzaki, Shigenori; Matsui, Motozumi; Miyamoto, Akio; Yamagishi, Norio; Osawa, Takeshi; Hashizume, Tsutomu; Izaike, Yoshiaki; Miyake, Yoh-Ichi

2011-06-01

The present study investigated the basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality. On the basis of semen parameters, bulls (n=5) having poor semen quality were selected as experimental bulls, and good semen quality bulls (n=4) were used as control bulls. Both groups were treated intramuscularly once with GnRH (250 µg of fertirelin acetate). Blood samples were collected at -1 day (d), -30 min and 0 h (treatment) followed by every 30 min for 5 h and 1, 3 and 5 d post-GnRH treatment (PGT), and LH, testosterone and estradiol-17β (E(2)) concentrations were measured. The pretreatment concentrations were used as basal levels. The percentage increments based on the 0-h levels were calculated per bull for each sampling time until 5 h PGT, and differences were compared between the experimental and control groups. The PGT concentrations of testosterone and basal and PGT concentrations of E(2) were significantly lower in the experimental group. The testosterone increment in the experimental group was delayed and significantly lower from 1 to 5 h PGT than those in the control group. It can be suggested that bulls with poor semen quality have delayed and lower GnRH-induced testosterone response and may also have lower estrogen levels.

Taiwan experience suggests that RhD typing for blood transfusion is unnecessary in southeast Asian populations.

PubMed

Lin, Marie

2006-01-01

The high frequency of RhD (D) antigen among Taiwanese persons (99.67%) often imposes unnecessary risks of under-transfusion on D- patients awaiting D- blood. Also because of the rare occurrence of anti-D among Taiwanese persons, routine pretransfusion D typing has been discontinued in the Mackay Memorial Hospital since 1988. This report is the retrospective evaluation of the outcome of abolishing RhD typing for Taiwanese. More than 10 years of alloantibody data at Mackay Memorial Hospital Blood Bank were reviewed. The cases with anti-D were further used to analyze the potency of D antigen and to observe whether there were differences in the incidence of anti-D before and after discontinuation of routine D typing among Taiwanese individuals. The incidence of anti-D before and after discontinuation of routine pretransfusion D typing has remained unchanged. The immunogenicity of D and "Mi(a)" in Taiwanese persons is found to be similar. In terms of opportunity for immunization, however, the "Mi(a)" antigen (phenotype frequency 7.3% in Taiwanese persons) has become the most important blood group antigen in Taiwan. The results strongly support the exclusion of D typing from routine compatibility testing for individuals of Taiwanese origin. Because the low incidence of D- and relatively high incidence of "Mi(a)"+ phenotypes are common findings throughout southeast Asia, and because a population genetic study revealed that the Taiwanese people are genetically related to southern Asian populations, it is suggested that RhD typing for blood transfusion is unnecessary among southeast Asian populations.

Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn.

PubMed

Delaney, Meghan; Matthews, Dana C

2015-01-01

Hemolytic disease of the fetus and newborn (HDFN) affects 3/100 000 to 80/100 000 patients per year. It is due to maternal blood group antibodies that cause fetal red cell destruction and in some cases, marrow suppression. This process leads to fetal anemia, and in severe cases can progress to edema, ascites, heart failure, and death. Infants affected with HDFN can have hyperbilirubinemia in the acute phase and hyporegenerative anemia for weeks to months after birth. The diagnosis and management of pregnant women with HDFN is based on laboratory and radiographic monitoring. Fetuses with marked anemia may require intervention with intrauterine transfusion. HDFN due to RhD can be prevented by RhIg administration. Prevention for other causal blood group specificities is less studied. © 2015 by The American Society of Hematology. All rights reserved.

Classification of Blood-Group Antibodies as β2M or γ Globulin

PubMed Central

Adinolfi, M.; Polley, Margaret J.; Hunter, Denise A.; Mollison, P. L.

1962-01-01

Thirty selected blood-group antibodies (excluding anti-A and anti-B) have been classified as β2M (19S γ) globulin, γ (7S γ) globulin or mixtures, using the following three methods: fractionation on a DEAE-cellulose column; indirect anti-globulin tests, using specific anti-β2M-globulin and anti-γ-globulin sera; and treatment with 2-mercapto-ethanol. With only minor exceptions, results obtained with the three methods were in agreement. Most blood-group antibodies within the Le, MNSs and P systems appear to be `naturally occurring' and these were found to be β2M globulin. Blood-group antibodies within the Rh, K and Jk systems, which had arisen after an antigenic stimulus, were usually γ globulin but were occasionally β2M globulin. Antibodies composed of β2M globulin usually behave as agglutinins but may behave as incomplete antibodies (e.g. some examples of anti-Jka); conversely, antibodies composed of γ globulin usually behave as incomplete antibodies but may behave as agglutinins (e.g. an example of anti-M). The ability to bind complement seems to be related more to the blood-group specificity of the particular antibody than to its molecular size. For example, anti-Jka, when composed either of γ or β2M globulin, seems invariably to bind complement, whereas potent anti-M or anti-Rh, whether composed of γ or β2M globulin, do not bind complement. PMID:14011076

Effects of transcutaneous electrical nerve stimulation (TENS) on arterial stiffness and blood pressure in resistant hypertensive individuals: study protocol for a randomized controlled trial.

PubMed

Vilela-Martin, José Fernando; Giollo-Junior, Luiz Tadeu; Chiappa, Gaspar Rogério; Cipriano-Junior, Gerson; Vieira, Paulo José Cardoso; dos Santos Ricardi, Fábio; Paz-Landim, Manoel Ildefonso; de Andrade, Days Oliveira; Cestário, Elizabeth do Espírito Santo; Cosenso-Martin, Luciana Neves; Yugar-Toledo, Juan Carlos; Cipullo, José Paulo

2016-03-29

Resistant hypertension (RH) treatment requires an adequate and intense therapeutic approach. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of RH, sympathetic overstimulation and therapies that block the sympathetic system have been widely studied. These approaches, however, are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a noninvasive method that modulates activity by using low-frequency transcutaneous electrical stimulation to inhibit primary afferent pathways. Thus, the current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with RH and will seek to develop a new low-cost and readily available therapy to treat this group of hypertensive individuals. This is a randomized, single blind (subject), parallel-assignment study controlled with a sham group and including participants aged 40 to 70 years with resistant hypertension. The trial has two arms: the treatment and control (sham group). The treatment group will be submitted to the stimulation procedure (TENS). The sham group will not be submitted to stimulation. The primary outcomes will be a reduction in the peripheral blood pressure and adverse events. The secondary outcomes will be a reduction the central blood pressure. The study will last 30 days. The sample size was calculated assuming an alpha error of 5 % to reject the null hypothesis with a statistical power of 80 %, thereby resulting in 28 participants per group (intervention versus sham). In recent decades, RH has become very common and costly. Adequate control requires several drugs, and in many cases, treatment is not successful. Sympathetic nervous system inhibition by renal denervation and central inhibition have significant effects in reducing BP; however, these treatments are costly and invasive. Another type of sympathetic nervous system inhibition can also be noninvasively achieved by electric current. Therefore, the application of TENS may be a new therapeutic option for treating resistant hypertensive individuals. Clinical Trials NCT02365974.

Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in non-human primates

PubMed Central

Makris, Angela; Yeung, Kristen R; Lim, Shirlene M; Sunderland, Neroli; Heffernan, Scott; Thompson, John F; Iliopoulos, Jim; Killingsworth, Murray C; Yong, Jim; Xu, Bei; Ogle, Robert F; Thadhani, Ravi; Karumanchi, S. Ananth; Hennessy, Annemarie

2016-01-01

An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia due to endothelial dysfunction. Circulating sFLT-1 (soluble fms-like tyrosine kinase 1) increases and PlGF (placental growth factor) reduces prior to and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a non-human primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of an 182 day pregnancy). Two weeks after uteroplacental ischemia (UPI), rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100μg/kg/day) for 5 days. Blood pressure (BP) was monitored by intra-arterial radiotelemetry, sFLT-1 and PlGF by ELISA. UPI resulted in experimental preeclampsia evidenced by increased BP, proteinuria and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after UPI. rhPlGF reduced SBP in the treated group (-5.2mmHg+0.8mmHg;from 132.6+6.6mmHg to 124.1+7.6mmHg) compared to an increase in SBP in controls (6.5mmHg+3mmHg; from 131.3+1.5mmHg to 138.6+1.5mmHg). Proteinuria reduced in the treated group (-72.7±55.7mg/mmol) but increased in the control group. Circulating sFLT-1 was not affected by the administration of PlGF, however a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference in the weights or lengths of the neonates in the rhPlGF or control group, however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. PMID:27091894

A randomized case-controlled study of recombinant human granulocyte colony stimulating factor for the treatment of sepsis in preterm neutropenic infants.

PubMed

Aktaş, Doğukan; Demirel, Bilge; Gürsoy, Tuğba; Ovalı, Fahri

2015-06-01

To investigate the efficacy and safety of recombinant human granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) to treat sepsis in neutropenic preterm infants. Fifty-six neutropenic preterm infants with suspected or culture-proven sepsis hospitalized in Zeynep Kamil Maternity and Children's Educational and Training Hospital, Kozyatağı/Istanbul, Turkey between January 2008 and January 2010 were enrolled. Patients were randomized either to receive rhG-CSF plus empirical antibiotics (Group I) or empirical antibiotics alone (Group II). Clinical features were recorded. Daily complete blood count was performed until neutropenia subsided. Data were analyzed using SPSS version 11.5. Thirty-three infants received rhG-CSF plus antibiotic treatment and 23 infants received antibiotic treatment. No drug-related adverse event was recorded. Absolute neutrophil count values were significantly higher on the 2(nd) study day and 3(rd) study day in Group I. Short-term mortality did not differ between the groups. Treatment with rhG-CSF resulted in a more rapid recovery of ANC in neutropenic preterm infants. However, no reduction in short-term mortality was documented. Copyright © 2014. Published by Elsevier B.V.

Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia

PubMed Central

Flanagan, Jonathan M.; Vege, Sunitha; Luban, Naomi L. C.; Brown, R. Clark; Ware, Russell E.; Westhoff, Connie M.

2017-01-01

RH genes are highly polymorphic and encode the most complex of the 35 human blood group systems. This genetic diversity contributes to Rh alloimmunization in patients with sickle cell anemia (SCA) and is not avoided by serologic Rh-matched red cell transfusions. Standard serologic testing does not distinguish variant Rh antigens. Single nucleotide polymorphism (SNP)–based DNA arrays detect many RHD and RHCE variants, but the number of alleles tested is limited. We explored a next-generation sequencing (NGS) approach using whole-exome sequencing (WES) in 27 Rh alloimmunized and 27 matched non-alloimmunized patients with SCA who received chronic red cell transfusions and were enrolled in a multicenter study. We demonstrate that WES provides a comprehensive RH genotype, identifies SNPs not interrogated by DNA array, and accurately determines RHD zygosity. Among this multicenter cohort, we demonstrate an association between an altered RH genotype and Rh alloimmunization: 52% of Rh immunized vs 19% of non-immunized patients expressed variant Rh without co-expression of the conventional protein. Our findings suggest that RH allele variation in patients with SCA is clinically relevant, and NGS technology can offer a comprehensive alternative to targeted SNP-based testing. This is particularly relevant as NGS data becomes more widely available and could provide the means for reducing Rh alloimmunization in children with SCA. PMID:29296782

Weak D Type 4.2.2 (DAR1.2) in an African child: Serology and molecular characterization.

PubMed

Orlando, Nicoletta; Putzulu, Rossana; Massini, Giuseppina; Scavone, Fernando; Piccirillo, Nicola; Maresca, Maddalena; Zini, Gina; Teofili, Luciana

2015-04-01

The weak D phenotype is represented by a group of RHD genotypes that code for alterated RhD proteins associated with a reduced RhD expression on red blood cell. By routine serology, some partial D variants are likely to be missed. In this report we describe the case of a three-year-old Black African child with a "unclear" reaction with monoclonal anti-D. We analyzed the blood sample of the child with different methods to conclude that it is a case of DAR 1.2 (weak D 4.2.2) and that it must be transfused with D negative erithrocytes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sertoli-Leydig cell tumors: hormonal profile after dynamic test with GnRH analogue: triptorelin represents a useful tool to evaluate tumoral hyperandrogenism.

PubMed

Turra, J; Granzotto, M; Gallea, M; Faggian, D; Conte, L; Litta, P; Vettor, R; Mioni, R

2015-01-01

We report the case of a 15-year-old woman with signs of hyperandrogenism affected by a Sertoli-Leydig cell tumor (SLCT). In our patient, blood analysis showed a high testosterone (T) level (T: 8.53 nmol/L; nv < 1.87 nmol/L) while the GnRH-analogue test demonstrated an exaggerated secretion of 17-hydroxyprogesterone (OHP), T, and androstenedione (A) by the ovary after stimulation. We compared the GnRH-analogue test of our patient with that obtained in a group of normal and healthy women (no. 8 subjects, 16-26 years old), men (no. 4 subjects, 18-28 years old), and in a group of PCOS patients with age and body weight compared. We found in our patient a value of OHP, 17-beta estradiol (E2) and T, from 2 to 18 times higher than healthy women. When we compared our patient with healthy men, we differently observed a comparable response of T. The response of our patient was also comparable with that observed in the PCOS group for E2. During the post-surgical follow up, the GnRH-analogue test of our patient showed a response of OHP, T, and E2 comparable with that of the PCOS group. The GnRH-analogue test is a useful tool to characterize steroidogenesis in SLCT.

Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment.

PubMed

Yang, Hongbo; Wang, Linjie; Qiu, Xiaonan; Yan, Kemin; Gong, Fengying; Zhu, Huijuan; Pan, Hui

2018-04-25

Recombinant human growth hormone (rhGH) replacement therapy is usually stopped after linear growth completion in patients with growth hormone deficiency. In patients with multiple pituitary hormone deficiency (MPHD), the long-term effects of discontinuation of rhGH replacement are unknown. In this study, the anthropometric and metabolic parameters of 24 male patients with adult growth hormone deficiency (AGHD) due to MPHD in childhood after cessation of rhGH therapy for a mean of 7.1 years were measured and compared with 35 age-matched controls. Body composition was evaluated by bioelectrical impedance analysis (BIA). In the AGHD group, body mass index (BMI) was significantly increased and 29.2% had obesity. The AGHD group had a 17.7 cm increase in waist circumference (WC). The fat free mass (FFM) was significantly lower in the AGHD group. Both the fat mass (FM) and percentage of fat mass (FM%) were significantly increased in the AGHD group. Both the systolic blood pressure (BP) and diastolic pressure were significantly lower in AGHD group. The lipid profile was generally similar in both groups, except for a decrease of high density lipoprotein-cholesterol (HDL-C) in the AGHD group. There was significant hyperuricemia in the AGHD group. Cessation of rhGH leads to a significant increase of FM in early adulthood in male patients with childhood-onset MPHD (CO-MPHD).

Effects of the Case-Based Instruction Method on the Experience of Learning

ERIC Educational Resources Information Center

Amiri Farahani, Leila; Heidari, Tooba

2014-01-01

This semi-experimental study was conducted with twenty-seven midwifery students who were randomly allocated to either case-based instruction or lecture-based instruction groups. The selected subjects -- foetal intrapartum assessment, foetal antepartum assessment, ABO and Rh blood group system mismatch -- were presented in four ninety-minute…

Analysis of grayanatoxin in Rhododendron honey and effect on antioxidant parameters in rats.

PubMed

Sibel, Silici; Enis, Yonar M; Hüseyin, Sahin; Timucin, Atayoğlu A; Duran, Ozkok

2014-10-28

Rhododendron honey, locally known as "mad honey", contains gryanotoksin (GTX) and thus induces toxic effects when consumed in large amounts. But, it is still popularly used for treating medical conditions such as high blood pressure or gastro-intestinal disorders. The aim of this study was to evaluate the effect of GTX on antioxidant parameters measured from rats fed with Rhododendron honey. A total of sixty Sprague-Dawley female rats were divided into five groups of 12 rats each, one being the control group (Group 1) and the others being the experimental groups (Groups 2 to 5). Group 2 was treated with 0.015 mg/kg/bw of Grayanotoxin-III (GTX-III) standard preparation via intraperitoneal injection. Groups 3, 4 and 5 were respectively given Rhododendron honey (RH) at doses of 0.1, 0.5, and 2.5 g/kg/bw via oral gavage. After one hour, blood samples were collected from the rats. Glutathione peroxidase (GSh-Px), superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) contents were examined in blood, heart, lungs, liver, kidney, testicles, epididiymis, spleen and brain specimens. The data from the rats in Groups 2 (GTX) and 5 (RH at 2.5 g/kg/bw) showed negative effect on the antioxidants parameters in blood and all tissue samples examined at the specified doses and time period. Administration of GTX to rats at dose of 0.015 mg/kg/bw resulted in lipid peroxidation. (This part needs to be enhanced more). It has been observed that both Grayanotoxin and high dose Rhododendron honey treatments showed oxidant effect on blood plasma and organ tissues investigated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Single-site Versus Multiport Robotic Hysterectomy in Benign Gynecologic Diseases: A Retrospective Evaluation of Surgical Outcomes and Cost Analysis.

PubMed

Bogliolo, Stefano; Ferrero, Simone; Cassani, Chiara; Musacchi, Valentina; Zanellini, Francesca; Dominoni, Mattia; Spinillo, Arsenio; Gardella, Barbara

2016-01-01

To compare the surgical outcomes and costs of robotic-assisted hysterectomy with the single-site (RSSH) or multiport approach (RH). A retrospective analysis of a prospectively collected database (Canadian Task Force classification II1). A university hospital. Consecutive women who underwent robotic-assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy for the treatment of benign gynecologic diseases. Data on surgical approach, surgical outcomes, and costs were collected in a prospective database and retrospectively analyzed. The total operative time, console time, docking time, estimated blood loss, conversion rate, and surgical complications rate were compared between the 2 study groups. Cost analysis was performed. One hundred four patients underwent total robotic-assisted hysterectomy and bilateral salpingo-oophorectomy (45 RSSH and 59 RH). There was no significant difference in the indications for surgery and in the characteristics of the patients between the 2 study groups. There was no significant difference between the single-site and multiport approach in console time, surgical complication rate, conversion rate, and postoperative pain. The docking time was lower in the RH group (p = .0001). The estimated blood loss and length of hospitalization were lower in the RSSH group (p = .0008 and p = .009, respectively). The cost analysis showed significant differences in favor of RSSH. RSSH should be preferred to RH when hysterectomy is performed for benign disease because it could be at least as equally effective and safe with a potential cost reduction. However, because of the high cost and absence of clear advantages, the robotic approach should be considered only for selected patients. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension.

PubMed

Hering, Dagmara; Marusic, Petra; Walton, Antony S; Duval, Jacqueline; Lee, Rebecca; Sata, Yusuke; Krum, Henry; Lambert, Elisabeth; Peter, Karlheinz; Head, Geoff; Lambert, Gavin; Esler, Murray D; Schlaich, Markus P

2016-01-01

Renal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. We measured office and 24-hour BP at baseline, 3 and 6 months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. RDN significantly reduced office and daytime SBP in group 1 at both 3 and 6 months follow-up (P<0.001) but not in groups 2 and 3. Similarly, a significant reduction in resting baseline MSNA was only observed in group 1 (P<0.05). There was no deterioration in kidney function in any group. While RDN can be performed safely irrespective of the underlying renal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

DNA-Based Methods in the Immunohematology Reference Laboratory

PubMed Central

Denomme, Gregory A

2010-01-01

Although hemagglutination serves the immunohematology reference laboratory well, when used alone, it has limited capability to resolve complex problems. This overview discusses how molecular approaches can be used in the immunohematology reference laboratory. In order to apply molecular approaches to immunohematology, knowledge of genes, DNA-based methods, and the molecular bases of blood groups are required. When applied correctly, DNA-based methods can predict blood groups to resolve ABO/Rh discrepancies, identify variant alleles, and screen donors for antigen-negative units. DNA-based testing in immunohematology is a valuable tool used to resolve blood group incompatibilities and to support patients in their transfusion needs. PMID:21257350

Evaluation of an automated microplate technique in the Galileo system for ABO and Rh(D) blood grouping.

PubMed

Xu, Weiyi; Wan, Feng; Lou, Yufeng; Jin, Jiali; Mao, Weilin

2014-01-01

A number of automated devices for pretransfusion testing have recently become available. This study evaluated the Immucor Galileo System, a fully automated device based on the microplate hemagglutination technique for ABO/Rh (D) determinations. Routine ABO/Rh typing tests were performed on 13,045 samples using the Immucor automated instruments. Manual tube method was used to resolve ABO forward and reverse grouping discrepancies. D-negative test results were investigated and confirmed manually by the indirect antiglobulin test (IAT). The system rejected 70 tests for sample inadequacy. 87 samples were read as "No-type-determined" due to forward and reverse grouping discrepancies. 25 tests gave these results because of sample hemolysis. After further tests, we found 34 tests were caused by weakened RBC antibodies, 5 tests were attributable to weak A and/or B antigens, 4 tests were due to mixed-field reactions, and 8 tests had high titer cold agglutinin with blood qualifications which react only at temperatures below 34 degrees C. In the remaining 11 cases, irregular RBC antibodies were identified in 9 samples (seven anti-M and two anti-P) and two subgroups were identified in 2 samples (one A1 and one A2) by a reference laboratory. As for D typing, 2 weak D+ samples missed by automated systems gave negative results, but weak-positive reactions were observed in the IAT. The Immucor Galileo System is reliable and suited for ABO and D blood groups, some reasons may cause a discrepancy in ABO/D typing using a fully automated system. It is suggested that standardization of sample collection may improve the performance of the fully automated system.

Epidemiology of Chikungunya Virus Outbreaks in Guadeloupe and Martinique, 2014: An Observational Study in Volunteer Blood Donors.

PubMed

Gallian, Pierre; Leparc-Goffart, Isabelle; Richard, Pascale; Maire, Françoise; Flusin, Olivier; Djoudi, Rachid; Chiaroni, Jacques; Charrel, Remi; Tiberghien, Pierre; de Lamballerie, Xavier

2017-01-01

During Dec-2013, a chikungunya virus (CHIKV) outbreak was first detected in the French-West Indies. Subsequently, the virus dispersed to other Caribbean islands, continental America and many islands in the Pacific Ocean. Previous estimates of the attack rate were based on declaration of clinically suspected cases. Individual testing for CHIKV RNA of all (n = 16,386) blood donations between Feb-24th 2014 and Jan-31st 2015 identified 0·36% and 0·42% of positives in Guadeloupe and Martinique, respectively. The incidence curves faithfully correlated with those of suspected clinical cases in the general population of Guadeloupe (abrupt epidemic peak), but not in Martinique (flatter epidemic growth). No significant relationship was identified between CHIKV RNA detection and age-classes or blood groups. Prospective (Feb-2014 to Jan-2015; n = 9,506) and retrospective (Aug-2013 to Feb-2014; n = 6,559) seroepidemiological surveys in blood donors identified a final seroprevalence of 48·1% in Guadeloupe and 41·9% in Martinique. Retrospective survey also suggested the absence or limited "silent" CHIKV circulation before the outbreak. Parameters associated with increased seroprevalence were: Gender (M>F), KEL-1, [RH+1/KEL-1], [A/RH+1] and [A/RH+1/KEL-1] blood groups in Martiniquan donors. A simulation model based on observed incidence and actual seroprevalence values predicted 2·5 and 2·3 days of asymptomatic viraemia in Martiniquan and Guadeloupian blood donors respectively. This study, implemented promptly with relatively limited logistical requirements during CHIKV emergence in the Caribbean, provided unique information regarding retrospective and prospective epidemiology, infection risk factors and natural history of the disease. In the stressful context of emerging infectious disease outbreaks, blood donor-based studies can serve as robust and cost-effective first-line tools for public health surveys.

Frequency and correlation of lip prints, fingerprints and ABO blood groups in population of Sriganganagar District, Rajasthan.

PubMed

Sandhu, Harpreet; Verma, Pradhuman; Padda, Sarfaraz; Raj, Seetharamaiha Sunder

2017-11-01

To investigate the frequency and uniqueness of different lip print patterns, fingerprint patterns in relation to gender and ABO Rh blood groups among a semi-urban population of Sriganganagar, Rajasthan. The study was conducted on 1200 healthy volunteers aged 18-30 years. The cheiloscopic and dermatographic data of each subject were obtained and were analysed according to the Suzuki and Tsuchihashi and Henry systems of classification, respectively. Two forensic experts analyzed the patterns independently. The ABO Rh blood group was also recorded for each subject. The Chi square statistical analysis was done and tests were considered significant when p value <0.001 and Cohen kappa test was applied to analyze inter-observer reliability. The B+ blood group was noted as most common in both genders while least common were A- among males and AB- in females. Type II lip pattern was most predominant while the least common was Type I' in males and Type I' and Type V in females. The UL fingerprint pattern was the most common, while RL was least noted in both genders. All the fingerprint patterns showed correlation with different lip print patterns. A correlation was found between different blood groups and lip print patterns except Type I (vertical) lip pattern. A positive correlation was observed between all the blood groups and fingerprint patterns, except for RL pattern. There is an association between lip print patterns, fingerprint patterns and ABO blood groups in both the genders. Thus, correlating the uniqueness of these physical evidences sometimes helps the forensic team members in accurate personal identification or it can at least narrow the search for an individual where there are no possible data referring to the identity of the subject. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Current markers of the Athlete Blood Passport do not flag microdose EPO doping.

PubMed

Ashenden, Michael; Gough, Clare E; Garnham, Andrew; Gore, Christopher J; Sharpe, Ken

2011-09-01

The Athlete Blood Passport is the most recent tool adopted by anti-doping authorities to detect athletes using performance-enhancing drugs such as recombinant human erythropoietin (rhEPO). This strategy relies on detecting abnormal variations in haematological variables caused by doping, against a background of biological and analytical variability. Ten subjects were given twice weekly intravenous injections of rhEPO for up to 12 weeks. Full blood counts were measured using a Sysmex XE-2100 automated haematology analyser, and total haemoglobin mass via a carbon monoxide rebreathing test. The sensitivity of the passport to flag abnormal deviations in blood values was evaluated using dedicated Athlete Blood Passport software. Our treatment regimen elicited a 10% increase in total haemoglobin mass equivalent to approximately two bags of reinfused blood. The passport software did not flag any subjects as being suspicious of doping whilst they were receiving rhEPO. We conclude that it is possible for athletes to use rhEPO without eliciting abnormal changes in the blood variables currently monitored by the Athlete Blood Passport.

Androstenedione response to recombinant human FSH is the most valid predictor of the number of selected follicles in polycystic ovarian syndrome: (a case-control study).

PubMed

Ozyurek, Eser Sefik; Yoldemir, Tevfik; Artar, Gokhan

2017-05-12

We aimed to test the hypothesis that the correlation of the changes in the blood Androstenedione (A 4 ) levels to the number of selected follicles during ovulation induction with low-dose recombinant human follicle stimulating hormone (rhFSH) is as strong as the correlation to changes in the blood Estradiol (E 2 ) levels in polycystic ovary syndrome (PCOS). Prospective Case-control study conducted from October 2014 to January 2016. 61 non-PCOS control (Group I) and 46 PCOS (Group II) patients treated with the chronic low-dose step up protocosl with rhFSH. A 4 , E 2 , progesterone blood levels and follicular growth were monitored.. Univariate and hierarchical multivariable analysis were performed for age, BMI, HOMA-IR, A 4 and E 2 (with the number of selected follicles as the dependent variable in both groups). ROC analysis was performed to define threshold values for the significant determinants of the number of selected follicles to predict cyle cancellations due to excessive ovarian response. The control group (Group I) was comprised of 61 cycles from a group of primary infertile non-PCOS patients, and the study group (Group II) of 46 cycles of PCOS patients. The analysis revealed that the strongest independent predictor of the total number of selected follicles in Group I was the E 2 (AUC) (B = 0.0006[0.0003-0.001]; P < 0.001); whereas for Group II, it was the A 4 (AUC) (B = 0.114[0.04-0.25]; P = 0.01). Optimum thresholds for the A 4 related parameters were defined to predict excessive response within Group II were 88.7%, 3.1 ng/mL and 5.4 ng*days for the percentage increase in A 4 , the maximum A 4 value and area under the curve values for A 4 , respectively. A 4 response to low-dose rhFSH in PCOS has a stronger association with the number of follicles selected than the E 2 reponse. A 4 response preceding the E 2 response is essential for progressive follicle development. Monitoring A 4 rather than E 2 may be more preemptive to define the initial ovarian response and accurate titration of the rhFSH doses. The study was registered as a prospective case-control study in the ClinicalTrials.gov registry with the identifier NCT02329483 .

Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis, and Lutheran) in blood donors of south Gujarat, India

PubMed Central

Kahar, Manoj A.; Patel, Rajnikant. D.

2014-01-01

Background: This is the first study on phenotype frequencies of various blood group systems in blood donors of south Gujarat, India using conventional tube technique. Material and Methods: A total of 115 “O” blood group donors from three different blood banks of south Gujarat were typed for D, C, c, E, e, K, Jka, Lea, Leb, P1, M, and N antigens using monoclonal antisera and k, Kpa, Kpb, Fya,Fyb, Jkb, S,s, Lua, and Lub antigens were typed using polyclonal antisera employing Indirect Antiglobulin Test. Antigens and phenotype frequencies were expressed as percentages. Results: From the 115 blood donor samples used for extended antigen typing in the Rh system, e antigen was found in 100% donors, followed by D [84.35%], C [81.74%], c [56.32%], and E [21.74%] with DCe/DCe (R1 R1, 40.87%) as the most common phenotype. k was found to be positive in 100% of donors and no K+k- phenotype was found in Kell system. For Kidd and Duffy blood group system, Jk(a+b+) and Fy(a-b-) were the most common phenotypes with frequency of 52.17% and 48.69%, respectively. In the MNS system, 39.13% donors were typed as M+N+, 37.39% as M+N-, and 23.48% as M-N+. S+s+ was found in 24.35% of donors, S+s- in 8.69%, and S-s+ as the commonest amongst donors with 66.96%. No Lu(a+b+) or Lu(a+b-) phenotypes were detected in 115 donors typed for Lutheran antigens. A rare Lu(a-b-) phenotype was found in 2.61% donors. Conclusion: Data base for antigen frequency of various blood group systems in local donors help provide antigen negative compatible blood units to patients with multiple antibodies in order to formulate in-house red cells for antibody detection and identification and for preparing donor registry for rare blood groups. PMID:24678176

New biodiagnostics based on optical tweezers: typing red blood cells, and identification of drug resistant bacteria

NASA Astrophysics Data System (ADS)

Chen, Jia-Wen; Lin, Chuen-Fu; Wang, Shyang-Guang; Lee, Yi-Chieh; Chiang, Chung-Han; Huang, Min-Hui; Lee, Yi-Hsiung; Vitrant, Guy; Pan, Ming-Jeng; Lee, Horng-Mo; Liu, Yi-Jui; Baldeck, Patrice L.; Lin, Chih-Lang

2013-09-01

Measurements of optical tweezers forces on biological micro-objects can be used to develop innovative biodiagnostics methods. In the first part of this report, we present a new sensitive method to determine A, B, D types of red blood cells. Target antibodies are coated on glass surfaces. Optical forces needed to pull away RBC from the glass surface increase when RBC antigens interact with their corresponding antibodies. In this work, measurements of stripping optical forces are used to distinguish the major RBC types: group O Rh(+), group A Rh(+) and group B Rh(+). The sensitivity of the method is found to be at least 16-folds higher than the conventional agglutination method. In the second part of this report, we present an original way to measure in real time the wall thickness of bacteria that is one of the most important diagnostic parameters of bacteria drug resistance in hospital diagnostics. The optical tweezers force on a shell bacterium is proportional to its wall thickness. Experimentally, we determine the optical tweezers force applied on each bacteria family by measuring their escape velocity. Then, the wall thickness of shell bacteria can be obtained after calibrating with known bacteria parameters. The method has been successfully applied to indentify, from blind tests, Methicillinresistant Staphylococcus aureus (MRSA), including VSSA (NCTC 10442), VISA (Mu 50), and heto-VISA (Mu 3)

Characteristics of Mammalian Rh Glycoproteins (SLC42 transporters) and Their Role in Acid-Base Transport

PubMed Central

Nakhoul, Nazih L.; Hamm, L. Lee

2012-01-01

The mammalian Rh glycoproteins belong to the solute transporter family SLC42 and include RhAG, present in red blood cells, and two non-erythroid members RhBG and RhCG that are expressed in various tissues, including kidney, liver, skin and the GI tract. The Rh proteins in the red blood cell form an “Rh complex” made up of one D-subunit, one CE-subunit and two RhAG subunits. The Rh complex has a well-known antigenic effect but also contributes to the stability of the red cell membrane. RhBG and RhCG are related to the NH4+ transporters of the yeast and bacteria but their exact function is yet to be determined. This review describes the expression and molecular properties of these membrane proteins and their potential role as NH3/NH4+ and CO2 transporters. The likelihood that these proteins transport gases such as CO2 or NH3 is novel and significant. The review also describes the physiological importance of these proteins and their relevance to human disease. PMID:23506896

Single dose of filgrastim (rhG-CSF) increases the number of hematopoietic progenitors in the peripheral blood of adult volunteers.

PubMed

Schwinger, W; Mache, C; Urban, C; Beaufort, F; Töglhofer, W

1993-06-01

Hematopoietic progenitor cell levels were monitored in the peripheral blood of ten healthy adults receiving a single dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF). The objective was to determine the time and number of progenitor cells released into the peripheral blood, induced by a single dose of 15 micrograms/kg rhG-CSF administered intravenously. In all cases the absolute number of circulating progenitor cells including granulocyte-macrophage and erythroid lineages increased up to 12-fold (median 9.4-fold) 4 days after treatment. These findings were based on flow cytometric quantification of CD34+ cells and on progenitor assays. The relative distribution of granulocyte/macrophage and erythroid progenitors remained unchanged. rhG-CSF was well tolerated; mild to moderate bone pain was the most common side-effect and was noted in 6 of 10 subjects. Thus a single dose of rhG-CSF is effective in mobilizing progenitor cells into the peripheral blood in healthy adults. If these progenitors are capable of reconstituting bone marrow, peripheral progenitor cell separation following rhG-CSF administration could be a reasonable alternative to conventional bone marrow harvest in healthy adults.

The MNS glycophorin variant GP.Mur affects differential erythroid expression of Rh/RhAG transcripts.

PubMed

Hsu, K; Kuo, M-S; Yao, C-C; Cheng, H-C; Lin, H-J; Chan, Y-S; Lin, M

2017-10-01

The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides. The goal of this study was to determine whether GP.Mur influenced erythroid Rh/RhAG expression at the transcript level. GP.Mur was serologically determined in healthy participants from Taitung County, Taiwan. RNA was extracted from the reticulocyte-enriched fraction of peripheral blood, followed by reverse transcription and quantitative PCR for RhAG, RhD and RhCcEe. Quantification by real-time PCR revealed significantly fewer RhAG and RhCcEe transcripts in the reticulocytes from subjects with homozygous GYP*Mur. Independent from GYP.Mur, both RhAG and RhD transcript levels were threefold or higher than that of RhCcEe. Also, in GYP.Mur and the control samples alike, direct quantitative associations were observed between the transcript levels of RhAG and RhD, but not between that of RhAG and RhCcEe. Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or absence of glycophorin B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation. © 2017 International Society of Blood Transfusion.

The impact of granulocyte colony stimulating factor at content of donor lymphocytes collected for cellular immunotherapy.

PubMed

Arat, Mutlu; Arslan, Onder; Gürman, Günhan; Dalva, Klara; Ozcan, Muhit; Uğur, Aynur; Ilhan, Osman

2004-02-01

Donor lymphocyte infusions (DLI) have become widely used for prevention or treatment of relapse after allogeneic hematopoietic stem cell transplantation. Increasing use of reduced intensity conditioning regimens (RICR) and subsequent application of DLI forced the hemapheresis centers to collect donor lymphocytes in certain quantity and quality. The place of growth factors especially granulocyte colony stimulating factor (rhG-CSF, filgrastim) in allogeneic hemapoietic stem cell (HSC) collection is established, but there is no consensus about the role of rhG-CSF. We aimed to clarify the dose effect of rhG-CSF on lymphocyte subpopulations (CD3+, CD3+4+, CD3+8+, CD19+, CD3-16+56+) cells and CD34+ HSC. Major indications for DLI (mean volume: 180+/-52 ml) were for relapse or transplants using RICR mainly in patients with acute leukemia (n=20) or chronic myeloid leukemia (n=15). In four years we performed 40 lymphocyte apheresis (LA) on 30 healthy (med. age 28, M/F 21/9) donors using continuous flow cell separators by processing 2-2.5 times of their total blood volume (TBV). The apheresis data is divided into three groups according to rhG-CSF dose used for priming. Donors in Group I (n=18), Group II (n=9) and Group III (n=13) received no rhG-CSF (steady state), rhG-CSF 5 microg/kg/dsc x 5 days and rhG-CSF 10 microg/kg/dsc x 5 days, respectively. There was no difference within groups concerning TBV processed and recipient body weight. A total of 11,565 ml (+/-3700) of blood was processed in 216 min (+/-36.5) at an inlet of 56.8 ml/min (+/-10.6) using 999 ml (+/-307) ACD. The CD34+ HSC increased with increasing rhG-CSF dose as expected. Median CD3+ lymphocyte yield per recipient body weight in Group I, II and III were 0.9 x 10e8/kg (range: 0.1-2.1), 2.9 x 10e8/kg (range: 1.6-4.3) and 2.1 x 10e8/kg (range: 0.6-6.9), respectively. The primed donors T lymphocyte yield was 2-3-fold more in comparison to Group I. This gain was most significant between Group I and III in terms of mean CD3+ (1.09 x 10e8/kg vs 2.41 x 10e8/kg, p=0.02), CD3+4+ (0.64 x 10e8/kg vs 1.44 x 10e8/kg, p=0.02) and CD3+8+ (0.42 x 10e8/kg vs 0.89 x 10e8/kg, p=0.03) cells, respectively. Though the yield of lymphocyte subsets in G-CSF primed donors exceeds the non-primed donors, the target range of 1 x 10e7-1 x 10e8/kg CD3+ lymphocytes could be achieved in the majority of the apheresis procedures without rhG-CSF priming. The yield of T and B lymphocyte subsets are increased by G-CSF stimulation but not on a logarithmic scale, which did not correlate into a clinical relevance.

[Evaluation of blood grouping in ABO and Rh systems in health facilities in Benin].

PubMed

Anani, L Y; Lafia, E; Ahlonsou, F; Sogbohossou, P; Bigot, A; Fagbohoun, J; Meton, A; Adjaka, A; Latoundji, S; Py, J-Y; Zohoun, I S

2014-05-01

The goal of this work is to assess the modalities of blood typing achievement in Benin with the view of their improvement. On the basis of a questionnaire including the detailed operative process, a prospective investigation has been achieved in public and private health centers laboratories. It came out that the execution of ABO and Rh blood typing took place globally on the fringe of the standards. We note that 72.4% of the private laboratories and 48.9% of the public ones lacked at least one equipment and 51.3% at least one material for blood withdrawal; 38.2% of the laboratories did not respect blood withdrawal standards; 1.32% of the laboratories applied the 4×2 rule. The assessment revealed that respectively 10.8% and 30.7% of the blood centers and non-blood centers achieved the globular test solely; the same 40.5% and 46.2% used reagents of different brands. Anti-A1 and anti-H sera, and A1 and A2 red cells were not available in any laboratory. More than 64% of laboratories have senior technicians and biomedical analysis engineers but only 6.6% of the laboratories were directed by biologists, and 9.2% of the laboratories function with only one technician. Instead of some assets, the laboratories assessment noted important non-conformities we ought to raise as a matter of urgency. It is a challenge whose resolution must give blood transfusion centers a reference position relatively to blood grouping when facing blood typing difficulties. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Impact of antigenic exposures and role of molecular blood grouping in enhancing transfusion safety in chronically transfused thalassemics.

PubMed

Makroo, Raj Nath; Agrawal, Soma; Bhatia, Aakanksha; Chowdhry, Mohit; Thakur, Uday Kumar

2016-01-01

Red cell alloimmunization is an acknowledged complication of blood transfusion. Current transfusion practices for thalassemia do not cater to this risk. Serological phenotyping is usually not reliable in these cases unless performed before the first transfusion. Under such circumstances, molecular blood grouping is an effective alternative. To perform molecular blood group genotyping in chronically transfused thalassemia patients and assess the risk of antigenic exposure and incidence of alloimmunization with current transfusion protocols. Molecular blood group genotyping was performed for 47 chronically transfused thalassemia patients. Their 1-year transfusion records were retrieved to assess the antigenic exposure and the frequency thereof. Of 47 patients, 6 were already alloimmunized (3 with anti-E and 3 with anti-K) and were receiving the corresponding antigen negative units. We observed that random selection of ABO and Rh D matched units resulted in 57.7% ±8.26% chance of Rh and Kell phenotype matching also. Forty-four patients had received one or more antigenic exposures at least once. The 6 already alloimmunized patients were further exposed to antigens other than the ones they were immunized to. During the study period, only one patient developed an alloantibody, anti-E with exposure to antigens C (92%) and/or E (32%) at each transfusion. Several factors apart from mere antigen exposure may influence the development of alloimmunization as most of our patients received antigenic exposures but not alloimmunized. Our data provide an impetus for future large-scale studies to understand the development of alloimmunization in such patients.

[Effect of recombinant human growth hormone therapy on metabolic parameters in patients with craniopharyngioma].

PubMed

Mao, J F; Wang, X; Xiong, S Y; Zheng, J J; Yu, B Q; Nie, M; Wu, X Y; Qi, S T

2017-11-14

Objective: To investigate the effects of recombinant human growth hormone (rhGH) on metabolic parameters in patients with craniopharyngioma surgeries. Methods: Totallys 30 patients with craniopharyngioma were included in this retrospective study. They were divided into growth hormone (GH) group and control group according to whether they received rhGH therapy or not. The following parameters, including body mass index (BMI), weight, waist circumstance, transaminase, fasting blood glucose, lipid profile and high-sensitivity C-reactive protein (hsCRP) were compared after rhGH therapy for 4-6 months. Results: In GH group, patients were 18-46 (30.0±8.8) years old. The duration after craniopharyngioma surgery was (12.9±5.4) years. Before rhGH therapy, they had got sufficient thyroid and glucocorticoid hormone replacement. After rhGH therapy, the body weight decreased from (92.3±20.1) to (87.6 ±14.6) kg ( P =0.190), with a reduction of BMI from (30.1±5.9) to (28.2±3.7) kg/m(2) ( P =0.120). The waist circumference decreased from (104.4±9.4) cm to (98.8±10.6) cm ( P =0.002). Alanine aminotransferase (ALT) decreased from (52±34) to (28±19) U/L ( P =0.029), with a reduction of aspartate transaminase (AST) from (46±21) to (33±18) U/L ( P =0.035) and γ-glutamyl transpeptadase (GGT) from (59±42) to (29±15) U/L ( P =0.02). hsCRP decreased from (5.3±4.9) to (2.3±2.8) mg/L ( P =0.006) and triglyceride (TG) decreased from (1.8±0.7) to (1.5±0.6) mmol/L ( P =0.028). Fasting blood glucose, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and free fat acid (FFA) were not significantly changed(all P >0.05). In the control group, the above mentioned parameters did not changed significantly during 4-6 months of observational period(all P >0.05). Conclusion: rhGH therapy improves metabolic parameters in patients after craniopharyngioma surgery by decreasing body weight, waist circumstance and fat deposit in liver, as well as lowering TG and hsCRP levels.

The immunomodulatory protein RH36 is relating to blood-feeding success and oviposition in hard ticks.

PubMed

Wang, Fangfang; Lu, Xiaojuan; Guo, Fengxun; Gong, Haiyan; Zhang, Houshuang; Zhou, Yongzhi; Cao, Jie; Zhou, Jinlin

2017-06-15

An immunomodulatory protein designated RH36 was identified in the tick Rhipicephalus haemaphysaloides. The cDNA sequence of RH36 has 844bp and encodes a deduced protein with a predicted molecular weight of 24kDa. Bioinformatics analysis indicated that RH36 presented a degree of similarity of 34.36% with the immunomodulatory protein p36 from the tick Dermacentor andersoni. The recombinant RH36 (rRH36) expressed in Sf9 insect cells suppressed the T-lymphocyte mitogen-driven in vitro proliferation of splenocytes and the expression of several cytokines such as IL-2, IL-12, and TNF-α. Furthermore, the proliferation of splenocytes isolated from rRH36-inoculated mice was significantly lower than that in control mice, suggesting that rRH36 could directly suppress immune responses in vivo. In addition, microarray analysis of splenocytes indicated that the expression of several immunomodulatory genes was downregulated by rRH36. The silencing of the RH36 gene by RNAi led to a 37.5% decrease in the tick attachment rate 24h after placement into the rabbit ears, whereas vaccination with RH36 caused a 53.06% decrease in the tick engorgement rate. Unexpectedly, RNAi induced a significant decrease in the oviposition rate, ovary weight at day 12 after engorgement, and egg-hatching rate. The effects of RH36 on blood feeding and oviposition were further confirmed by vaccination tests using the recombinant protein. These results indicate that RH36 is a novel member of immunosuppressant proteins and affects tick blood feeding and oviposition. Copyright © 2017 Elsevier B.V. All rights reserved.

Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of rhBMP-2.

PubMed

Egashira, Kazuhiro; Sumita, Yoshinori; Zhong, Weijian; I, Takashi; Ohba, Seigo; Nagai, Kazuhiro; Asahina, Izumi

2018-01-01

Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation facilitates the clinical use of rhBMP-2 as an alternative strategy for bone engineering.

Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of rhBMP-2

PubMed Central

Egashira, Kazuhiro; Zhong, Weijian; I, Takashi; Ohba, Seigo; Nagai, Kazuhiro; Asahina, Izumi

2018-01-01

Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation facilitates the clinical use of rhBMP-2 as an alternative strategy for bone engineering. PMID:29346436

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system.

PubMed

Aachmann-Andersen, Niels J; Christensen, Soren J; Lisbjerg, Kristian; Oturai, Peter; Johansson, Pär I; Holstein-Rathlou, Niels-Henrik; Olsen, Niels V

2018-03-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo)

PubMed Central

Moeller, John F.; Meredith, Michael

2010-01-01

The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RFamide-like peptides. To define further the cell populations and connectivity, we used double-label immuno-cytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH immunoreactive (ir) cell-profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies, and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT) negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. PMID:20950589

Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo).

PubMed

Moeller, John F; Meredith, Michael

2010-12-17

The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. Copyright © 2010 Elsevier B.V. All rights reserved.

Rationale and Methodology of the SARAH Trial: Long-Term Cardiovascular Outcomes in Patients With Resistant Hypertension and Obstructive Sleep Apnea.

PubMed

Sapiña-Beltrán, Esther; Torres, Gerard; Martínez-Alonso, Montserrat; Sánchez-de-la-Torre, Manuel; Franch, Maria; Bravo, Carmen; Masa, Juan F; Felez, Miquel; Fortuna-Gutierrez, Ana Maria; Abad, Jorge; García-Río, Francisco; Drager, Luciano F; Lee Chi-Hang, Ronald; Martínez-García, Miguel Ángel; Barbé, Ferran; Dalmases, Mireia

2018-05-22

Patients with resistant hypertension (RH) have a high risk of developing cardiovascular events; therefore, new therapeutic approaches to better control blood pressure may be useful in improving cardiovascular outcomes. The prevalence of obstructive sleep apnea (OSA) is very high among patients with RH. Continuous positive airway pressure (CPAP) has been shown to be an effective treatment for reducing blood pressure in patients with RH. Nevertheless, the long-term effect of CPAP treatment on cardiovascular outcomes has not been explored. The main objective of the SARAH study is to assess the impact of OSA and its treatment on cardiovascular outcomes (morbidity and mortality) in patients with RH. This study is a multi-center, prospective, observational cohort study. A total of 1371 patients with RH will be enrolled in the study and followed once a year for five years. At inclusion, ambulatory blood pressure monitoring (ABPM) and a sleep study will be performed in all subjects. Socio-demographic, clinical and cardiovascular variables will be collected at baseline and follow-up. Subsequently, subjects with OSA will be managed according to local standard practice. Based on the OSA diagnosis and its treatment, three cohorts of subjects with RH will be defined: non-OSA, treated OSA and non-treated OSA. This study will contribute to elucidating the long-term impact of OSA treatments on blood pressure control and cardiovascular outcomes in patients with RH. These results will contribute to improve the cardiovascular prognosis of patients with RH. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Fertility after ovarian follicular wave synchronization and fixed-time natural mating compared to random natural mating in dromedary camels (Camelus dromedarius).

PubMed

Nagy, P; Juhasz, J

2012-06-01

The objective of the study was to compare the efficiency of two ovarian follicular wave synchronization protocols coupled with fixed-time natural mating with that of random mating in dromedary camels. Dromedaries were assigned randomly to one of the three treatment groups. Group 1 animals (RM; n = 46) were mated randomly. Group 2 camels (1×GnRH-FTM; n = 46) were given a GnRH analog (Buserelin, 20 μg/animal, i.v.; Receptal, Intervet, Holland) at random, then were mated 14 days later. In Group 3 animals (2×GnRH-FTM; n = 41), random GnRH analog was followed by repeated GnRH injection 14 days later and fixed-time natural mating on Day 28. Transrectal examination and ultrasonography were performed at weekly intervals to evaluate ovarian follicular status, diagnose ovulation and pregnancy. Blood samples were collected for progesterone determination by ELISA to confirm ovulation and pregnancy. All female dromedaries were assigned randomly to one of thirteen fertile bulls and were bred once on Days 1, 14 and 28 in Groups 1-3, respectively. Ovarian follicular status and ovulation rate was similar among groups at the start of the study. Seventy-five of the 133 dromedaries (56.4%) ovulated after random natural mating or random GnRH treatment. Mean length of mating was 386 ± 17.8 (±SEM) seconds. There was no significant difference in mating time among groups and in pregnancy rate among dromedary bulls. In Group 3 (2×GnRH-FTM), ovarian follicular status before mating (P < 0.05), ovulation rate (n = 37, 90.2%, P < 0.001) and pregnancy rate at 21 and 60 days (PR 21 days n = 22, 53.7% and PR 60 days n = 19, 46.3%, P < 0.05) were greater compared to random natural mating (Group 1: OR n = 25, 54.3%, PR 21 days n = 13, 28.3% and PR 60 days n = 12, 26.1%). In Group 2 dromedaries (1×GnRH-FTM), treatment tended to improve follicular status before mating, ovulation rate (n = 34, 73.9%) and pregnancy rate at 21 and 60 days (PR 21 days n = 21, 45.7% and PR 60 days n = 16, 34.8%), but the effect was not significant compared to random natural mating. In conclusion, this is the first study demonstrating that favorable pregnancy rate can be achieved following ovarian follicular wave synchronization with repeated GnRH analog and fixed-time natural mating at 14 days intervals in dromedary camels. Copyright © 2012 Elsevier B.V. All rights reserved.

Non-invasive fetal RHD genotyping for RhD negative women stratified into RHD gene deletion or variant groups: comparative accuracy using two blood collection tube types.

PubMed

Hyland, Catherine A; Millard, Glenda M; O'Brien, Helen; Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Tremellen, Anne; Puddephatt, Rachel; Gaerty, Kirsten; Flower, Robert L; Hyett, Jonathan A; Gardener, Glenn J

2017-12-01

Non-invasive fetal RHD genotyping in Australia to reduce anti-D usage will need to accommodate both prolonged sample transport times and a diverse population demographic harbouring a range of RHD blood group gene variants. We compared RHD genotyping accuracy using two blood sample collection tube types for RhD negative women stratified into deleted RHD gene haplotype and RHD gene variant cohorts. Maternal blood samples were collected into EDTA and cell-free (cf)DNA stabilising (BCT) tubes from two sites, one interstate. Automated DNA extraction and polymerase chain reaction (PCR) were used to amplify RHD exons 5 and 10 and CCR5. Automated analysis flagged maternal RHD variants, which were classified by genotyping. Time between sample collection and processing ranged from 2.9 to 187.5 hours. cfDNA levels increased with time for EDTA (range 0.03-138 ng/μL) but not BCT samples (0.01-3.24 ng/μL). For the 'deleted' cohort (n=647) all fetal RHD genotyping outcomes were concordant, excepting for one unexplained false negative EDTA sample. Matched against cord RhD serology, negative predictive values using BCT and EDTA tubes were 100% and 99.6%, respectively. Positive predictive values were 99.7% for both types. Overall 37.2% of subjects carried an RhD negative baby. The 'variant' cohort (n=15) included one novel RHD and eight hybrid or African pseudogene variants. Review for fetal RHD specific signals, based on one exon, showed three EDTA samples discordant to BCT, attributed to high maternal cfDNA levels arising from prolonged transport times. For the deleted haplotype cohort, fetal RHD genotyping accuracy was comparable for samples collected in EDTA and BCT tubes despite higher cfDNA levels in the EDTA tubes. Capacity to predict fetal RHD genotype for maternal carriers of hybrid or pseudogene RHD variants requires stringent control of cfDNA levels. We conclude that fetal RHD genotyping is feasible in the Australian environment to avoid unnecessary anti-D immunoglobulin prophylaxis. Copyright © 2017. Published by Elsevier B.V.

Lack of association between Rh status, Rh immune globulin in pregnancy and autism.

PubMed

Miles, Judith H; Takahashi, T Nicole

2007-07-01

Though causes of autism are considered largely genetic, considerable concern remains that exposure to Rh immune globulin (RhIg), which until 2001 in the United States contained the preservative thimerosal, can cause autism. To determine whether mothers of children with autism are more likely to be Rh negative (Rh(-)) or to have received RhIg preserved with thimerosal, which is 49.6% ethyl mercury, we surveyed families of children with an autism spectrum disorder (ASD) ascertained through a University-based autism clinic considered free of ascertainment biases related to type of autism or severity. Between 2004 and 2006, 305 mothers of 321 children with an ASD agreed to participate in a telephone interview. Analysis of complete records including the blood group status and RhIg exposure of 214 families showed that Rh(-) status is no higher in mothers of children with autism than in the general population, exposure to antepartum RhIg, preserved with thimerosal is no higher for children with autism and pregnancies are no more likely to be Rh incompatible. This was also true for autism subgroups defined by behavioral phenotype, gender, IQ, regressive onset, head circumference, dysmorphology, birth status, essential, or complex phenotype. These findings support the consensus that exposure to ethylmercury in thimerosal is not the cause of the increased prevalence of autism. These data are important not only for parents in this country but also for the international health community where thimerosal continues to be used to preserve multi-dose vials which in turn makes vaccines affordable. (c) 2007 Wiley-Liss, Inc.

Distribution and clinal trends of the ABO and Rh genes in select Middle Eastern countries.

PubMed

AlSuhaibani, E S; Kizilbash, N A; Afshan, K; Malik, S

2015-09-09

An understanding of the ABO and Rh blood group systems is important for blood transfusions and is also pertinent due to their potential association with certain morbidities and susceptibilities to infections. To investigate the diversity and differentiation of the ABO and Rh loci in Middle Eastern populations, data from twelve representative Middle Eastern populations were analyzed. Six populations were in conformity with Hardy-Weinberg equilibrium at the ABO locus. The pooled heterozygosity at both loci was calculated to be highest in the sample from Jordan and lowest in Bahrain. Heterogeneity was pronounced in the Northern compared to the Southern Middle Eastern populations. Overall, the absolute gene diversity was 0.0046 and gene differentiation was calculated to be 0.0100. Genetic diversity of the studied loci across all populations (HT) was estimated to be 0.4594, while the diversity within the populations (HS) was 0.4548. Nei's genetic distance analyses revealed highest affinities between the populations of Kuwait and Qatar, Oman and Yemen, and between Qatar and the United Arab Emirates. These results were displayed through a UGPMA dendrogram and principal component analyses, which established clustering of certain populations. Clinal trends of the allelic systems were observed by generating contour maps that allow a detailed appreciation of the distributions of alleles across the geography of the Arabian Peninsula and the Middle East. Taken together, these analyses are helpful in understanding the differentiation of blood group loci and for designing prospective studies for establishing the associations of these loci with health variables in the populations studied.

Weak D caused by a founder deletion in the RHD gene.

PubMed

Fichou, Yann; Chen, Jian-Min; Le Maréchal, Cédric; Jamet, Déborah; Dupont, Isabelle; Chuteau, Claude; Durousseau, Cécile; Loirat, Marie-Jeanne; Bailly, Pascal; Férec, Claude

2012-11-01

The RhD blood group system exemplifies a genotype-phenotype correlation by virtue of its highly polymorphic and immunogenic nature. Weak D phenotypes are generally thought to result from missense mutations leading to quantitative change of the D antigen in the red blood cell membrane or intracellularly. Different sets of polymerase chain reaction primers were designed to map and clone a deletion involving RHD Exon 10, which was found in approximately 3% of approximately 2000 RHD hemizygous subjects with D phenotype ambiguity. D antigen density was measured by flow cytometry. Transcript analysis was carried out by 3'-rapid amplification of complementary DNA ends. Haplotype analysis was performed by microsatellite genotyping. A 5405-bp deletion that removed nearly two-thirds of Intron 9 and almost all of Exon 10 of the RHD gene was characterized. It is predicted to result in the replacement of the last eight amino acids of the wild-type RhD protein by another four amino acids. The mean RhD antigen density from two deletion carriers was determined to be only 30. A consensus haplotype could be deduced from the deletion carriers based on the microsatellite genotyping data. The currently reported deletion was derived from a common founder. This deletion appears to represent not only the first large deletion associated with weak D but also the weakest of weak D alleles so far reported. This highly unusual genotype-phenotype relationship may be attributable to the additive effect of three distinct mechanisms that affect mRNA formation, mRNA stability, and RhD/ankyrin-R interaction, respectively. © 2012 American Association of Blood Banks.

Active immunization with GnRH-tandem-dimer peptide in young male rats reduces serum reproductive hormone concentrations, testicular development and spermatogenesis.

PubMed

Han, Xing-Fa; Li, Jun-Li; Zhou, Yu-Qin; Ren, Xiao-Hua; Liu, Gong-Cheng; Cao, Xiao-Han; Du, Xiao-Gang; Zeng, Xian-Yin

2016-01-01

GnRH sterilization vaccines have been developed for various practical and clinical reasons. However, conjugation of GnRH peptide to carrier protein has many drawbacks, hampering the further commercialization of GnRH vaccines. In this study, a new nonconjugated GnRH vaccine, D-Lys6-GnRH-tandem-dimer peptide (TDK), emulsified in Specol adjuvant was investigated for its immunocastration efficacy in young male rats. Prepubertal male rats were randomly allocated into three groups (n = 12): control (no treatment), surgically castrated or immunized against 100 μg TDK in Specol adjuvant at 6 weeks of age (with a booster 8 weeks later). Blood samples (for antibody titers and hormone concentrations) were collected at 2-week intervals until rats were killed (18 weeks of age). Compared to intact controls, active immunization against TDK reduced (P < 0.05) serum concentrations of testosterone, inhibin B, LH and FSH, prevented the onset of spermatogenesis at puberty. Furthermore, mRNA expressions of GnRH receptor, LH-β and FSH-β in the pituitary, LH receptor, FSH receptor, inhibin α, βA and βB subunit in the testes were decreased in immunocastrated rats compared to intact controls (P < 0.05). These results demonstrate for the first time that GnRH-tandem-dimer peptide emulsified in Specol is a promising veterinary sterilization medicine.

Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor.

PubMed

MacVittie, T J; Farese, A M; Herodin, F; Grab, L B; Baum, C M; McKearn, J P

1996-05-15

Combination cytokine therapy continues to be evaluated in an effort to stimulate multilineage hematopoietic reconstitution after bone marrow myelosuppression. This study evaluated the efficacy of combination therapy with the synthetic interleukin-3 receptor agonist, Synthokine-SC55494, and recombinant methionyl human granulocyte colony-stimulating factor (rhG-CSF) on platelet and neutrophil recovery in nonhuman primates exposed to total body 700 cGy 60Co gamma radiation. After irradiation on day (d) 0, cohorts of animals subcutaneously received single-agent protocols of either human serum albumin (HSA; every day [QD], 15 micrograms/kg/d, n = 10), Synthokine (twice daily [BID], 100, micrograms/kg/d, n = 15), rhG-CSF (QD, 10 micrograms/kg/d, n = 5), or a combination of Synthokine and rhG-CSF (BID, 100 and 10 micrograms/kg/d, respectively, n = 5) for 23 days beginning on d1. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (absolute neutrophil count < 500/microL) and thrombocytopenia (platelet count < 20,000/microL) were assessed. Animals were provided clinical support in the form of antibiotics, fresh irradiated whole blood, and fluids. All cytokine protocols significantly (P < .05) reduced the duration thrombocytopenia versus the HSA-treated animals. Only the combination protocol of Synthokine + rhG-CSF and rhG-CSF alone significantly shortened the period neutropenia (P < .05). The combined Synthokine/rhG-CSF protocol significantly improved platelet nadir versus Synthokine alone and HSA controls and neutrophil nadir versus rhG-CSF alone and HSA controls. All cytokine protocols decreased the time to recovery to preirradiation neutrophil and platelet values. The Synthokine/rhG-CSF protocol also reduced the transfusion requirements per treatment group to 0 among 5 animals as compared with 2 among 5 animals for Synthokine alone, 8 among 5 animals for rhG-CSF, and 17 among 10 animals for HSA. These data showed that the combination of Synthokine, SC-55494, and rhG-CSF further decreased the cytopenic periods and nadirs for both platelets and neutrophils relative to Synthokine and rhG-CSF monotherapy and suggest that this combination therapy would be effective against both neutropenia and thrombocytopenia consequent to drug- or radiation- induced myelosuppression.

Red blood cell microparticles and blood group antigens: an analysis by flow cytometry

PubMed Central

Canellini, Giorgia; Rubin, Olivier; Delobel, Julien; Crettaz, David; Lion, Niels; Tissot, Jean-Daniel

2012-01-01

Background The storage of blood induces the formation of erythrocytes-derived microparticles. Their pathogenic role in blood transfusion is not known so far, especially the risk to trigger alloantibody production in the recipient. This work aims to study the expression of clinically significant blood group antigens on the surface of red blood cells microparticles. Material and methods Red blood cells contained in erythrocyte concentrates were stained with specific antibodies directed against blood group antigens and routinely used in immunohematology practice. After inducing erythrocytes vesiculation with calcium ionophore, the presence of blood group antigens was analysed by flow cytometry. Results The expression of several blood group antigens from the RH, KEL, JK, FY, MNS, LE and LU systems was detected on erythrocyte microparticles. The presence of M (MNS1), N (MNS2) and s (MNS4) antigens could not be demonstrated by flow cytometry, despite that glycophorin A and B were identified on microparticles using anti-CD235a and anti-MNS3. Discussion We conclude that blood group antigens are localized on erythrocytes-derived microparticles and probably keep their immunogenicity because of their capacity to bind specific antibody. Selective segregation process during vesiculation or their ability to elicit an immune response in vivo has to be tested by further studies. PMID:22890266

Effect of pronase on high-incidence blood group antigens and the prevalence of antibodies to pronase-treated erythrocytes.

PubMed

Reid, M E; Greeen, C A; Hoffer, J; Øyen, R

1996-01-01

Pronase is a useful and relatively nonspecific protease that cleaves many red blood cell (RBC) membrane proteins that carry blood group antigens. Unexpected findings in tests using pronase-treated RBCs during the investigation of a patient's blood sample led us to test which high-incidence blood group antigens were sensitive and which were resistant to pronase treatment, and to determine the prevalence of antipronase in the serum of blood donors. Our results show that antigens in the Cromer and Lutheran blood group systems and the JMH antigen were sensitive to pronase treatment of RBCs. Antigens in the Dombrock blood group system and Sc1 were either sensitive to or markedly weakened by pronase treatment of RBCs. The following high-incidence antigens were resistant to treatment of RBCs with pronase: AnWj, Ata, Coa, Co3, Dib, EnaFR, Era, Fy3, Jk3, Jra, k, Kpb, Jsb, K14, Lan, Oka, Rh17, U, Vel, and Wrb. Over half of the serum samples from normal blood donors contained antibodies to pronase-treated RBCs. When testing human serum against pronase-treated RBCs, it is essential either to use an autocontrol or to perform the testing with an eluate.

Integration of red cell genotyping into the blood supply chain: a population-based study.

PubMed

Flegel, Willy A; Gottschall, Jerome L; Denomme, Gregory A

2015-07-01

When problems with compatibility arise, transfusion services often use time-consuming serological tests to identify antigen-negative red cell units for safe transfusion. New methods have made red cell genotyping possible for all clinically relevant blood group antigens. We did mass-scale genotyping of donor blood and provided hospitals with access to a large red cell database to meet the demand for antigen-negative red cell units beyond ABO and Rh blood typing. We established a red cell genotype database at the BloodCenter of Wisconsin on July 17, 2010. All self-declared African American, Asian, Hispanic, and Native American blood donors were eligible irrespective of their ABO and Rh type or history of donation. Additionally, blood donors who were groups O, A, and B, irrespective of their Rh phenotype, were eligible for inclusion only if they had a history of at least three donations in the previous 3 years, with one donation in the previous 12 months at the BloodCenter of Wisconsin. We did red cell genotyping with a nanofluidic microarray system, using 32 single nucleotide polymorphisms to predict 42 blood group antigens. An additional 14 antigens were identified via serological phenotype. We monitored the ability of the red cell genotype database to meet demand for compatible blood during 3 years. In addition to the central database at the BloodCenter of Wisconsin, we gave seven hospitals online access to a web-based antigen query portal on May 1, 2013, to help them to locate antigen-negative red cell units in their own inventories. We analysed genotype data for 43,066 blood donors. Requests were filled for 5661 (99.8%) of 5672 patient encounters in which antigen-negative red cell units were needed. Red cell genotyping met the demand for antigen-negative blood in 5339 (94.1%) of 5672 patient encounters, and the remaining 333 (5.9%) requests were filled by use of serological data. Using the 42 antigens represented in our red cell genotype database, we were able to fill 14,357 (94.8%) of 15,140 requests for antigen-negative red cell units from hospitals served by the BloodCenter of Wisconsin. In the pilot phase, the seven hospitals identified 71 units from 52 antigen-negative red cell unit requests. Red cell genotyping has the potential to transform the way antigen-negative red cell units are provided. An antigen query portal could reduce the need for transportation of blood and serological screening. If this wealth of genotype data can be made easily accessible online, it will help with the supply of affordable antigen-negative red cell units to ensure patient safety. BloodCenter of Wisconsin Diagnostic Laboratories Strategic Initiative and the NIH Clinical Center Intramural Research Program. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

PubMed Central

Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

1992-01-01

The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo. PMID:1534001

Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

PubMed

Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

1992-04-01

The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.

A new biosensor for noninvasive determination of fetal RHD status in maternal blood of RhD negative pregnant women.

PubMed

Dündar Yenilmez, Ebru; Kökbaş, Umut; Kartlaşmış, Kezban; Kayrın, Levent; Tuli, Abdullah

2018-01-01

Prenatal detection of the fetal RHD status can be useful in the management of RhD incompatibility to identify fetuses at risk of hemolytic disease. Hemolytic disease causes morbidity and mortality of the fetus in the neonatal period. The routine use of antenatal and postnatal anti-D prophylaxis has reduced the incidence of hemolytic disease of the fetus and newborn. This study describe the detection of fetal RhD antigens in blood of RhD negative pregnant women using a nanopolymer coated electrochemical biosensor for medical diagnosis. Cell free fetal DNA in maternal plasma was also used to genotyping fetal RHD status using multiplex real-time PCR. Twenty-six RhD negative pregnant women in different gestational ages were included in the study. RhD positive fetal antibodies detected with a developed biosensor in maternal blood of RhD negative mothers. The electrochemical measurements were performed on a PalmSens potentiostat, and corundum ceramic based screen printed gold electrode combined with the reference Ag/AgCl electrode, and the auxiliary Au/Pd (98/2%) electrode. Fetal RHD genotyping performed using fluorescence-based multiplex real-time PCR exons 5 and 7 of the RHD gene. The fetal RHD status of 26 RhD negative cases were detected 21 as RhD positive and 5 as RhD negative with electrochemical biosensor. Fetal RHD status confirmed with extracted fetal DNA in maternal plasma using multiplex real-time PCR RHD genotyping and by serological test after delivery. The new method for fetal RhD detection in early pregnancy is useful and can be carry out rapidly in clinical diagnosis. Using automated biosensors are reproducible, quick and results can be generated within a few minutes compared to noninvasive fetal RHD genotyping from maternal plasma with real-time PCR-based techniques. We suggest the biosensor techniques could become an alternative part of fetal RHD genotyping from maternal plasma as a prenatal screening in the management of RhD incompatibility.

Angiogenesis and osteogenesis in an orthopedically expanded suture

NASA Technical Reports Server (NTRS)

Chang, H. N.; Garetto, L. P.; Potter, R. H.; Katona, T. R.; Lee, C. H.; Roberts, W. E.

1997-01-01

The purpose of this study was to examine the angiogenic and the subsequent osteogenic responses during a 96-hour time-course after sutural expansion. Fifty rats were divided into: (1) a control group that received only angiogenic induction through injection of 5 ng/gm recombinant human endothelial cell growth factor (rhECGF); (2) an experimental group that received orthopedic expansion and rhECGF; (3) a sham group that received expansion and sodium chloride (NaCl) injection; and (4) a baseline group that received no expansion or injection. All rats were injected with 3H-thymidine (1.0 microCi/gm) 1 hour before death to label the DNA of S-phase cells. Demineralized sections (4 microm thick) were stained with hematoxylin and eosin. Angiogenesis and cell migration were analyzed with a previously established cell kinetics model. Analysis of variance was used to test the hypothesis that enhancement of angiogenesis stimulates reestablishment of osteogenic capability. Blood vessel number, area, and endothelial cell-labeled index significantly increased in experimental groups, but no difference was found between control and baseline groups. Labeled-pericyte index and activated pericyte numbers in the experimental group were also higher than in the sham groups. These results show that supplemental rhECGF enhances angiogenesis in expanded sutures but not in nonexpanded sutures. Data also suggest that pericytes are the source of osteoblasts in an orthopedically expanded suture.

Effect of progesterone prior to GnRH-PGF2alpha treatment on induction of oestrus and pregnancy in anoestrous Awassi ewes.

PubMed

Husein, M Q; Kridli, R T

2003-06-01

An experiment was conducted to examine the effect of progesterone prior to a GnRH-PGF2alpha treatment on oestrus and pregnancy in seasonally anoestrous Awassi ewes. Twenty-four ewes were randomly assigned to three groups to be pre-treated with 60 mg medroxyprogesterone acetate sponges (group A), 600 mg progesterone sponges (group B) or blank sponges (group C) for 4 days. All ewes were injected with 100 microg of GnRH 24 h after sponge removal followed, 5 days later, by 20 mg PGF2alpha injection. Ewes were exposed to three fertile rams at the time of PGF2alpha injection (day 0, 0 h) and were checked for breeding marks at 6-h intervals for 5 days. Blood samples were collected from all ewes 1 day (day -10) prior to sponge insertion, at the time of sponge removal (day -6), 1 day following sponge removal (day -5, at the time of GnRH injection) and at the time of PGF2alpha injection (day 0) for analysis of progesterone. Progesterone concentrations on days -10 and -5 were basal and averaged 0.2 +/- 0.04 and 0.2 +/- 0.2 ng/ml, respectively. Progesterone concentrations on day -6 were elevated only in group B ewes and were higher (p < 0.0001) than those of groups A and C. Progesterone concentrations on day 0 were higher (p = 0.002) in groups A and B than group C. Oestrous responses occurred only in ewes of groups A and B (p > 0.05). Induced oestrus conception rate was greater (p < 0.01) in group A than groups B and C. Ewes returned to oestrus 17-20 days following day 0 were two of eight, six of eight and three of eight of groups A, B and C, respectively, all of which eventually lambed. The overall lambing rate was 82% in progesterone-primed ewes compared with only 38% non-progesterone-primed ewes (p < 0.05). Progesterone priming apparently sensitizes GnRH-PGF2alpha-treated seasonally anoestrous ewes and increases their response in oestrus and pregnancy rates.

[Biodemographical study in the Island of Pascua].

PubMed

Lazo, B; Campusano, C; Figueroa, H

1993-06-01

The aim of this study was to know the degree of miscegenation in the Easter Island population. One hundred two weddings carried out between 1987 and 1991 were recorded and the proportion of marriages between islanders and immigrants was analyzed. Also, ABO and Rh blood groups of all deliveries occurred between 1988 and 1991 were compiled. There was a particular tendency of islanders to marry with immigrants and the proportion of miscegenation was 75.5%. Additionally a decline in the frequency of A blood group is observed, comparing results from studies performed since 1932 up to date.

New concepts of the central control of reproduction, integrating influence of stress, metabolic state, and season.

PubMed

Clarke, I J; Arbabi, L

2016-07-01

Gonadotropin releasing hormone is the primary driver of reproductive function and pulsatile GnRH secretion from the brain causes the synthesis and secretion of LH and FSH from the pituitary gland. Recent work has revealed that the secretion of GnRH is controlled at the level of the GnRH secretory terminals in the median eminence. At this level, projections of kisspeptin cells from the arcuate nucleus of the hypothalamus are seen to be closely associated with fibers and terminals of GnRH cells. Direct application of kisspeptin into the median eminence causes release of GnRH. The kisspeptin cells are activated at the time of a natural "pulse" secretion of GnRH, as reflected in the secretion of LH. This appears to be due to input to the kisspeptin cells from glutamatergic cells in the basal hypothalamus, indicating that more than 1 neural element is involved in the secretion of GnRH. Because the GnRH secretory terminals are outside the blood-brain barrier, factors such as kisspeptin may be administered systemically to cause GnRH secretion; this offers opportunities for manipulation of the reproductive axis using factors that do not cross the blood-brain barrier. In particular, kisspeptin or analogs of the same may be used to activate reproduction in the nonbreeding season of domestic animals. Another brain peptide that influences reproductive function is gonadotropin inhibitory hormone (GnIH). Work in sheep shows that this peptide acts on GnRH neuronal perikarya, but projections to the median eminence also allow secretion into the hypophysial portal blood and action of GnIH on pituitary gonadotropes. GnIH cells are upregulated in anestrus, and infusion of GnIH can block the ovulatory surge in GnRH and/or LH secretion. Metabolic status may also affect the secretion of reproduction, and this could involve action of gut peptides and leptin. Neuropeptide Y and Y-receptor ligands have a negative impact on reproduction, and Neuropeptide Y production is markedly increased in negative energy balance; this may be the cause of lowered GnRH and gonadotropin secretion in this state. There is a complex interaction between appetite-regulating peptide neurons and kisspeptin neurons that enables the former to regulate the latter both positively and negatively. In terms of how GnRH secretion is reduced during stress, recent data indicate that GnIH cells are integrally involved, with increased input to the GnRH cells. The secretion of GnIH into the portal blood is not increased during stress, so the negative effect is most likely effected at the level of GnRH neuronal cell bodies. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary rose hip exerts antiatherosclerotic effects and increases nitric oxide-mediated dilation in ApoE-null mice.

PubMed

Cavalera, Michele; Axling, Ulrika; Rippe, Catarina; Swärd, Karl; Holm, Cecilia

2017-06-01

Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans. The aim of this study was to elucidate the mechanisms by which rose hip lowers plasma cholesterol and to evaluate its effects on atherosclerotic plaque formation. ApoE-null mice were fed either an HFD (CTR) or HFD with rose hip supplementation (RH) for 24 weeks. At the end of the study, we found that blood pressure and atherosclerotic plaques, together with oxidized LDL, total cholesterol and fibrinogen levels were markedly reduced in the RH group. Fecal cholesterol content, liver expression of Ldlr and selected reverse cholesterol transport (RCT) genes such as Abca1, Abcg1 and Scarb1 were significantly increased upon RH feeding. In the aorta, the scavenger receptor Cd36 and the proinflammatory Il1β genes were markedly down-regulated compared to the CTR mice. Finally, we found that RH increased nitric oxide-mediated dilation of the caudal artery. Taken together, these results suggest that rose hip is a suitable dietary supplement for preventing atherosclerotic plaques formation by modulating systemic blood pressure and the expression of RCT and inflammatory genes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Prevalence and Clinical Characteristics of Refractory Hypertension.

PubMed

Armario, Pedro; Calhoun, David A; Oliveras, Anna; Blanch, Pedro; Vinyoles, Ernest; Banegas, Jose R; Gorostidi, Manuel; Segura, Julián; Ruilope, Luis M; Dudenbostel, Tanja; de la Sierra, Alejandro

2017-12-07

We aimed to estimate the prevalence of refractory hypertension (RfH) and to determine the clinical differences between these patients and resistant hypertensives (RH). Secondly, we assessed the prevalence of white-coat RfH and clinical differences between true- and white-coat RfH patients. The present analysis was conducted on the Spanish Ambulatory Blood Pressure Monitoring Registry database containing 70 997 treated hypertensive patients. RH and RfH were defined by the presence of elevated office blood pressure (≥140 and/or 90 mm Hg) in patients treated with at least 3 (RH) and 5 (RfH) antihypertensive drugs. White-coat RfH was defined by RfH with normal (<130/80 mm Hg) 24-hour blood pressure. A total of 11.972 (16.9%) patients fulfilled the standard criteria of RH, and 955 (1.4%) were considered as having RfH. Compared with RH patients, those with RfH were younger, more frequently male, and after adjusting for age and sex, had increased prevalence of target organ damage, and previous cardiovascular disease. The prevalence of white coat RfH was lower than white-coat RH (26.7% versus 37.1%, P <0.001). White-coat RfH, in comparison with those with true RfH, showed a lower prevalence of both left ventricular hypertrophy (22% versus 29.7%; P =0.018) and microalbuminuria (28.3% versus 42.9%; P =0.047). The prevalence of RfH was low and these patients had a greater cardiovascular risk profile compared with RH. One out of 4 patients with RfH have normal 24-hour blood pressure and less target organ damage, thus indicating the important role of ambulatory blood pressure monitoring in guiding antihypertensive therapy in difficult-to-treat patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Changes in gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor gene expression after an increase in carbon monoxide concentration in the cavernous sinus of male wild boar and pig crossbread.

PubMed

Romerowicz-Misielak, M; Tabecka-Lonczynska, A; Koziol, K; Gilun, P; Stefanczyk-Krzymowska, S; Och, W; Koziorowski, M

2016-06-01

Previous studies indicate that there are at least a few regulatory systems involved in photoperiodic synchronisation of reproductive activity, which starts with the retina and ends at the gonadotropin-releasing hormone (GnRH) pulse generator. Recently we have shown indicated that the amount of carbon monoxide (CO) released from the eye into the ophthalmic venous blood depends on the intensity of sunlight. The aim of this study was to test whether changes in the concentration of carbon monoxide in the ophthalmic venous blood may modulate reproductive activity, as measured by changes in GnRH and GnRH receptor gene expression. The animal model used was mature male swine crossbred from wild boars and domestic sows (n = 48). We conducted in vivo experiments to determine the effect of increased CO concentrations in the cavernous sinus of the mammalian perihypophyseal vascular complex on gene expression of GnRH and GnRH receptors as well as serum luteinizing hormone (LH) levels. The experiments were performed during long photoperiod days near the summer solstice (second half of June) and short photoperiod days near the winter solstice (second half of December). These crossbred swine demonstrated a seasonally-dependent marked variation in GnRH and GnRH receptor gene expression and systemic LH levels in response to changes in CO concentration in ophthalmic venous blood. These results seem to confirm the hypothesis of humoral phototransduction as a mechanism for some of bright light's effects in animal chronobiology and the effect of CO on GnRH and GnRH receptor gene expression.

Social stratification in the Sikh population of Punjab (India) has a genetic basis: evidence from serological and biochemical markers.

PubMed

Chahal, Sukh Mohinder Singh; Virk, Rupinder Kaur; Kaur, Sukhvir; Bansal, Rupinder

2011-01-01

The present study was planned to assess whether social stratification in the Sikh population inhabiting the northwest border Indian state of Punjab has any genetic basis. Blood samples were collected randomly from a total of 2851 unrelated subjects belonging to 21 groups of two low-ranking Sikh scheduled caste populations, viz. Mazhabi and Ramdasi, and a high-ranking Jat Sikh caste population of Punjab. The genetic profile of Sikh groups was investigated using a total of nine serobiochemical genetic markers, comprising two blood groups (ABO, RH(D)) and a battery of seven red cell enzyme polymorphisms (ADA, AK1, ESD, PGM1, GLO1, ACP1, GPI), following standard serological and biochemical laboratory protocols. Genetic structure was studied using original allele frequency data and statistical measures of heterozygosity, genic differentiation, genetic distance, and genetic admixture. Great heterogeneity was observed between Sikh scheduled caste and Jat Sikh populations, especially in the RH(D) blood group system, and distribution of ESD, ACP1, and PGM1 enzyme markers was also found to be significantly different between many of their groups. Genetic distance trees demonstrated little or no genetic affinities between Sikh scheduled caste and Jat Sikh populations; the Mazhabi and Ramdasi also showed little genetic relationship. Genetic admixture analysis suggested a higher element of autochthonous tribal extraction in the Ramdasi. The present study revealed much genetic heterogeneity in differently ranking Sikh caste populations of Punjab, mainly attributable to their different ethnic backgrounds, and provided a genetic basis to social stratification present in this religious community of Punjab, India.

Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and non-resistant hypertension

PubMed Central

Sim, John J.; Bhandari, Simran K.; Shi, Jiaxiao; Reynolds, Kristi; Calhoun, David A.; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J.

2015-01-01

We sought to compare the risk of end stage renal disease (ESRD), ischemic heart event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and all-cause mortality among 470,386 individuals with resistant and nonresistant hypertension (non-RH). Resistant hypertension (60,327 individuals) was sub-categorized into 2 groups; 23,104 patients with cRH (controlled on 4 or more medicines) and 37,223 patients with uRH (uncontrolled on 3 or more medicines) in a 5 year retrospective cohort study. Cox proportional hazard modeling was used to estimate hazard ratios adjusting for age, gender, race, body mass index, chronic kidney disease (CKD), and co-morbidities. Resistant hypertension (cRH and uRH) compared to non-RH, had multivariable adjusted hazard ratios (95% confidence intervals) of 1.32 (1.27–1.37), 1.24 (1.20–1.28), 1.46 (1.40–1.52), 1.14 (1.10–1.19), and 1.06 (1.03–1.08) for ESRD, IHE, CHF, CVA, and mortality, respectively. Comparison of uRH to cRH had hazard ratios of 1.25 (1.18–1.33), 1.04 (0.99–1.10), 0.94 (0.89–1.01), 1.23 (1.14–1.31), and 1.01 (0.97–1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Males and Hispanics had greater risk for ESRD within all 3 cohorts. Resistant hypertension had greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk of ESRD and CVA and were 25% and 23% greater, respectively, in uRH compared to cRH supporting the linkage between blood pressure and both outcomes. PMID:25945406

Radioactive body burden measurements in (131)iodine therapy for differentiated thyroid cancer: effect of recombinant thyroid stimulating hormone in whole body (131)iodine clearance.

PubMed

Ravichandran, Ramamoorthy; Al Saadi, Amal; Al Balushi, Naima

2014-01-01

Protocols in the management of differentiated thyroid cancer, recommend adequate thyroid stimulating hormone (TSH) stimulation for radioactive (131)I administrations, both for imaging and subsequent ablations. Commonly followed method is to achieve this by endogenous TSH stimulation by withdrawal of thyroxine. Numerous studies worldwide have reported comparable results with recombinant human thyroid stimulating hormone (rhTSH) intervention as conventional thyroxine hormone withdrawal. Radiation safety applications call for the need to understand radioactive (131)I (RA(131)I) clearance pattern to estimate whole body doses when this new methodology is used in our institution. A study of radiation body burden estimation was undertaken in two groups of patients treated with RA(131)I; (a) one group of patients having thyroxine medication suspended for 5 weeks prior to therapy and (b) in the other group retaining thyroxine support with two rhTSH injections prior to therapy with RA(131)I. Sequential exposure rates at 1 m in the air were measured in these patients using a digital auto-ranging beta gamma survey instrument calibrated for measurement of exposure rates. The mean measured exposure rates at 1 m in μSv/h immediately after administration and at 24 h intervals until 3 days are used for calculating of effective ½ time of clearance of administered activity in both groups of patients, 81 patients in conventionally treated group (stop thyroxine) and 22 patients with rhTSH administration. The (131)I activities ranged from 2.6 to 7.9 GBq. The mean administered (131)I activities were 4.24 ± 0.95 GBq (n = 81) in "stop hormone" group and 5.11 ± 1.40 GBq (n = 22) in rhTSH group. The fall of radioactive body burden showed two clearance patterns within observed 72 h. Calculated T½eff values were 16.45 h (stop hormone group) 12.35 h (rhTSH group) for elapsed period of 48 h. Beyond 48 h post administration, clearance of RA(131)I takes place with T½eff> 20 h in both groups. Neck and stomach exposure rate measurements showed reduced uptakes in the neck for rhTSH patients compared with "stop thyroxine" group and results are comparable with other studies. Whole body clearance is faster for patients with rhTSH injection, resulting in less whole body absorbed doses, and dose to blood. These patients clear circulatory radioactivity faster, enabling them to be discharged sooner, thus reduce costs of the hospitalization. Reduction in background whole body count rate may improve the residual thyroid images in whole body scan. rhTSH provides TSH stimulation without withdrawal of thyroid hormone and hence can help patients to take up therapy without hormone deficient problems in the withdrawn period prior to RA(131)I therapy. This also will help in reducing the restriction time periods for patients to mix up with the general population and children.

Progesterone concentration, pregnancy and calving rate in Simmental dairy cows after oestrus synchronisation and hCG treatment during the early luteal phase.

PubMed

Šuluburić, Adam; Milanović, Svetlana; Vranješ-Đurić, Sanja; Jovanović, Ivan B; Barna, Tomislav; Stojić, Milica; Fratrić, Natalija; Szenci, Ottó; Gvozdić, Dragan

2017-09-01

Early embryonic development may be negatively affected by insufficient progesterone (P4) production. Therefore, the aim of our study was to increase P4 by gonadotropin-releasing hormone (GnRH) and/or human chorionic gonadotropin (hCG) treatments after inducing oestrus by prostaglandin (PG) treatment. Lactating Simmental dairy cows (n = 110), between 1 to 5 lactations, with an average milk production of 6,500 1/305 days, at 40-80 days postpartum were used and grouped as follows: (1) PG + GnRH treatment at AI (GnRH group), (2) PG + hCG treatment at day 7 after AI (hCG group), (3) PG + GnRH at AI + hCG treatment at day 7 after AI (GnRH/hCG group), and (4) spontaneous oestrus (C: control group). All animals were double inseminated (at the time of oestrus detection and 12 ± 2 h thereafter). Blood serum and milk samples were collected at the day of observed oestrus (day 0), and 14, 21 and 28 days after AI. Serum P4 was determined using a commercial radioimmunoassay (RIA) test (INEP, Zemun), and milk P4 was determined using enzyme-linked immunoassay (ELISA) test (NIV Novi Sad). Pregnancy status was confirmed by ultrasonography between days 28 and 35 after AI. Differences of serum or milk P4 medians, pregnancy (and calving) rate were determined using Dunn's Multiple Comparison Tests and Z test, respectively. Serum P4 medians were significantly higher at days 14, 21 and 28 after AI in the hCG-treated animals, indicating increased luteal activity, with a similar tendency in whole milk P4 values. Treatment with hCG during the early luteal phase significantly contributed to the maintenance of gestation at days 28-35 after AI, and also increased the calving rate in Simmental dairy cows.

[Identification of alloantibodies and their associations: balance sheet of a year at the Auvergne-Loire French Blood Establishment].

PubMed

Duboeuf, S; Flourié, F; Courbil, R; Benamara, A; Rigal, E; Cognasse, F; Garraud, O

2012-12-01

Some alloantibodies and their combinations can lead to delays or even an impasse in a transfusion, owing to the necessity of finding compatible red blood cell concentrates. The aim of this study was to determine the specificities of the most common alloantibodies, as well as the most common combinations of alloantibodies. A retrospective study analysed erythrocyte alloantibodies identified in 2008 in the immunohematology laboratories at the Auvergne-Loire French Blood Establishment. The following data were studied: frequency, specificities of the alloantibodies, date of discovery, and patient age and sex. One thousand eight hundred and fifteen alloantibodies were identified in 1575 patients (median age: 63.5years, female/male ratio: 3.03). The most common alloantibodies were directed against the following antigens: RH3/E (18.7%), KEL1/K (17.3%), RH1/D (16.4%), MNS1/M (9.4%), FY1/Fya (6.9%), RH2/C (6.1%), KEL3/Kpa (4.7%), JK1/Jka (4.3%) and RH4/c (4.1%). In 13.1% of patients, at least two alloantibodies were identified. The pairs most frequently combined were anti-RH1/RH2, anti-RH3/RH4 and anti-RH3/KEL1. Specific associations of paired alloantibodies were identified. The main combinations provide indications on the choice of red cell concentrates in the inventory for a given patient. The data collected in our study show that when an antibody is identified, it is recommended for subsequent transfusion episodes to respect the phenotype RH 1-5 (D, C, E, c, e) and KEL1 (K) of the patient, and if possible antigens JK1 (Jka) and FY1 (Fya), and to a lesser extent MNS3 (S). Detailed knowledge of the immunological mechanisms leading to the formation of these alloantibodies and their combinations would allow better prevention of erythrocyte alloimmunization. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis

PubMed Central

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-01-01

Background: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). Results: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P = 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP. PMID:28639575

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

PubMed

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-07-05

Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

Is there an association of ABO blood groups and Rhesus factor with alopecia areata?

PubMed

İslamoğlu, Zeynep Gizem Kaya; Unal, Mehmet

2018-01-15

Alopecia areata (AA) is an autoimmune disease characterized by noncicatricial hair loss localized on hair, beard, mustache, eyebrow, eyelash, and sometimes on the body. Although etiopathogenesis is not fully understood, many studies show remarkable associations between various diseases and ABO blood groups. However, there is no study with AA and blood groups. Healthy people and patients with AA were included in this study. A total of 155 patients with AA and 299 healthy controls were included in the study. ABO blood group distribution in patients with AA and distribution of healthy donors were similar. However, Rhesus factor positivity in the AA group was significantly higher than in healthy donors. The relationship between stress and AA was high as known. But, ABO blood group and Rhesus factor were not in a significant connection with stress. We conclude that there was no association between ABO blood group and AA, but the observed distribution of Rhesus blood group differed slightly but significantly from that of the healthy population. The result of the study shows a small but statistically significant difference in the Rh blood group between patients with AA and the healthy population blood groups. This result is important because it suggests that genetic factors may influence the development of AA. The role of blood groups in the development of AA remains to be determined. We believe that the studies which will be carried out in other centers with wider series will be more valuable to support this hypothesis. © 2018 Wiley Periodicals, Inc.

Acquired RhD mosaicism identifies fibrotic transformation of thrombopoietin receptor-mutated essential thrombocythemia.

PubMed

Montemayor-Garcia, Celina; Coward, Rebecca; Albitar, Maher; Udani, Rupa; Jain, Prachi; Koklanaris, Eleftheria; Battiwalla, Minoo; Keel, Siobán; Klein, Harvey G; Barrett, A John; Ito, Sawa

2017-09-01

Acquired copy-neutral loss of heterozygosity has been described in myeloid malignant progression with an otherwise normal karyotype. A 65-year-old woman with MPL-mutated essential thrombocythemia and progression to myelofibrosis was noted upon routine pretransplant testing to have mixed field reactivity with anti-D and an historic discrepancy in RhD type. The patient had never received transfusions or transplantation. Gel immunoagglutination revealed group A red blood cells and a mixed-field reaction for the D phenotype, with a predominant D-negative population and a small subset of circulating red blood cells carrying the D antigen. Subsequent genomic microarray single nucleotide polymorphism profiling revealed copy-neutral loss of heterozygosity of chromosome 1 p36.33-p34.2, a known molecular mechanism underlying fibrotic progression of MPL-mutated essential thrombocythemia. The chromosomal region affected by this copy-neutral loss of heterozygosity encompassed the RHD, RHCE, and MPL genes. We propose a model of chronological molecular events that is supported by RHD zygosity assays in peripheral lymphoid and myeloid-derived cells. Copy-neutral loss of heterozygosity events that lead to clonal selection and myeloid malignant progression may also affect the expression of adjacent unrelated genes, including those encoding for blood group antigens. Detection of mixed-field reactions and investigation of discrepant blood typing results are important for proper transfusion support of these patients and can provide useful surrogate markers of myeloproliferative disease progression. © 2017 AABB.

MAOA expression predicts vulnerability for alcohol use.

PubMed

Cervera-Juanes, R; Wilhem, L J; Park, B; Lee, R; Locke, J; Helms, C; Gonzales, S; Wand, G; Jones, S R; Grant, K A; Ferguson, B

2016-04-01

The role of the monoamines dopamine (DA) and serotonin (5HT) and the monoamine-metabolizing enzyme monoamine oxidase A (MAOA) have been repeatedly implicated in studies of alcohol use and dependence. Genetic investigations of MAOA have yielded conflicting associations between a common polymorphism (MAOA-LPR) and risk for alcohol abuse. The present study provides direct comparison of tissue-specific MAOA expression and the level of alcohol consumption. We analyzed rhesus macaque MAOA (rhMAOA) expression in blood from males before and after 12 months of alcohol self-administration. In addition, nucleus accumbens core (NAc core) and cerebrospinal fluid (CSF) were collected from alcohol access and control (no alcohol access) subjects at the 12-month time point for comparison. The rhMAOA expression level in the blood of alcohol-naive subjects was negatively correlated with subsequent alcohol consumption level. The mRNA expression was independent of rhMAOA-LPR genotype and global promoter methylation. After 12 months of alcohol use, blood rhMAOA expression had decreased in an alcohol dose-dependent manner. Also after 12 months, rhMAOA expression in the NAc core was significantly lower in the heavy drinkers, as compared with control subjects. The CSF measured higher levels of DA and lower DOPAC/DA ratios among the heavy drinkers at the same time point. These results provide novel evidence that blood MAOA expression predicts alcohol consumption and that heavy alcohol use is linked to low MAOA expression in both the blood and NAc core. Together, the findings suggest a mechanistic link between dampened MAOA expression, elevated DA and alcohol abuse.

Influence of IL-3 functional fragment on cord blood stem cell ex vivo expansion and differentiation.

PubMed

Ren, Zhihua; Zhang, Yu; Zhang, Yanxi; Jiang, Wenhong; Dai, Wei; Ding, Xinxin; Jiang, Yongping

2016-01-01

Recombinant human interleukin-3 (rhIL-3) is a multiple hematopoietic growth factor, which enhances stem cell expansion and hematopoiesis regeneration in vitro and in vivo, when administrated in combination with other cytokines. However, the structure-function study of rhIL-3 remains rarely studied, so far. The purpose of this study was to recognize the short peptide with similar function as rhIL-3, and assess the hematopoietic efficacy in umbilical cord blood (UCB) stem cell culture as well. Two novel monoclonal antibodies (mAb) (C1 and E1) were generated against rhIL-3 using hybridoma technique. Eleven short peptides were depicted and synthesized to overlap covering the full length sequence of rhIL-3. ELISA was employed to distinguish the antibody-binding peptide from the negative peptides. In addition, the multi-potential hematopoiesis capabilities of the positive peptides were evaluated by adding 25 ng/mL of each peptide to the culture medium of hematopoietic stem cells (HSCs) derived from UCB. Total nucleated cell number and the CD34(+) cell number from each individual treatment group were calculated on day 7. Correlated antibodies at 0.5 or 2 molar fold to each peptide were also tested in the stem cell expansion experiment, to further confirm the bioactivity of the peptides. Two peptides were recognized by the novel generated antibodies, using ELISA. Peptide 3 and 8 exhibited comparable hematopoiesis potentials, with 25.01±0.14 fold, and 19.89±0.12 fold increase of total nucleated cell number on day 7, respectively, compared with the basal medium control (4.93±0.55 fold). These biological effects were neutralized by adding the corresponding mAb at a dose dependent manner. Our results identified two specific regions of rhIL-3 responsible for HSC proliferation and differentiation, which were located from 28 to 49 amino acids (P3), and 107 to 127 amino acids (P8), respectively. The short peptide 3 and 8 might act synergistically, which could serve as an economic substitute to rhIL-3 in research laboratory.

Does the liquid method of electret forming influence the adhesion of blood platelets?

PubMed

Lowkis, B; Szymanowicz, M

1995-01-01

This work presents the results of the effect of the electric charge on the adhesion of blood platelets. All experiments were carried out on polyethylene foil. The liquid method was used to form electrets. The evaluation of the electret effect influence on the adhesion of blood platelets was made on the basis of the observation of the electret surface after the contact with fresh citrate human blood group O Rh+ in an electron scanning microscope. Experimental results confirmed the essential influence of the electric charge on the process of adhesion of blood platelets. It was noticed that the preliminary aging of electrets decreases the density of the surface charge and improves the athrombogenic characteristics of polyethylene foil.

Pharmacologic application of native GnRH in the winter anovulatory mare, II: accelerating the timing of pregnancy.

PubMed

Thorson, J F; Prezotto, L D; Cardoso, R C; Allen, C C; Alves, B R C; Amstalden, M; Williams, G L

2014-03-01

Onset of the winter anovulatory period in mares is associated with a marked diminution in adenohypophyseal synthesis and release of LH. Native GnRH, unlike its synthetic agonists, stimulates the synthesis and secretion of LH in mares without pituitary refractoriness. Herein we tested the hypotheses that (1) the average Julian day of pregnancy can be accelerated by up to 2 months in winter anovulatory mares treated continuously with native GnRH beginning on February 1 and (2) mares will sustain luteal function and pregnancy after treatment withdrawal. Forty-two winter anovulatory mares were stratified by age, body condition score, and size of the largest follicle across two locations in a randomized design and assigned to one of three groups (n = 14 per group): (1) CONTROL: untreated, (2) GnRH-14: GnRH delivered subcutaneously in saline at a rate of 100 μg/h for 8 weeks (February 1-March 29) using four consecutive 14-day pumps (Alzet 2ML2), or (3) GnRH-28: GnRH delivered as in (2), but using two 28-day pumps (Alzet 2ML4). On development of a 35-mm follicle and expression of estrus, mares were bred the following day and treated with hCG. Pregnancies were confirmed using transrectal ultrasonography on Days 14, 24, 33, and 45, with blood samples collected to assess luteal function. Mares treated with GnRH (GnRH-14 and GnRH-28) did not differ reproductively in their responses and data were pooled for statistical comparisons. Mares treated with GnRH exhibited marked increases (P ≤ 0.04) in the frequency of development of a 35-mm follicle, submission rate for live cover and/or artificial insemination, ovulation, and pregnancy compared with control mares on treatment Day 56 (March 29). Interval to the first 35-mm follicle was 51.8 ± 4.9 and 19.3 ± 3.5 days (least square mean ± standard error of the mean) for control and GnRH-treated mares, respectively. Interval to pregnancy was 65.3 ± 6.7 and 28.6 ± 4.8 days (least square mean ± standard error of the mean) for control and GnRH-treated mares, respectively, excluding one GnRH-14 mare that failed to become pregnant over four cycles. By the end of the treatment period (March 29), only 21% of control mares were pregnant compared with 79% of GnRH-treated mares. Furthermore, mean serum concentrations of progesterone were similar to (GnRH-28; P = 0.26) or greater than (GnRH-14; P = 0.01) that of control mares from Day 0 to 46 postbreeding. Data illustrate that continuous administration of native GnRH is a highly efficient option for managing seasonal anovulation in mares and could be effectively used in the breeding industry if a user-friendly delivery option were available. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of PDGF-BB and beta-tricalcium phosphate (β-TCP) on bone formation around dental implants: a pilot study in sheep.

PubMed

Choo, Tina; Marino, Victor; Bartold, P Mark

2013-02-01

The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (β-TCP) on bone healing around dental implants with critical size circumferential defects. Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) β-TCP; (c) rhPDGF-BB (0.3 mg/ml) with β-TCP. All the defects in each group were covered with a Bio-Gide(®) resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual β-TCP graft particles in the defects. Defects filled with rhPDGF-BB/β-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the β-TCP particles over 4 weeks. Defects filled with β-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the β-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/β-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and β-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when β-TCP was used in defects at 4 weeks. Defects which had β-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with β-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals. © 2011 John Wiley & Sons A/S.

Is the flexible GnRH antagonist protocol better suited for fresh eSET cycles?

PubMed

Dahdouh, Elias M; Gomes, Francisco L A F; Granger, Louis; Carranza-Mamane, Belina; Faruqi, Faez; Kattygnarath, Tiao-Virirak; St-Michel, Pierre

2014-10-01

This study was performed to evaluate the efficacy of the flexible GnRH antagonist protocol in comparison with the long GnRH agonist protocol in elective single embryo transfer (eSET) practice. It was conducted in a publicly funded in vitro fertilization program. We performed a prospective cohort analysis of data from a private infertility clinic from August 2010 to August 2011. Three hundred fourteen women with normal ovarian reserve and undergoing fresh eSET cycles were included. Sixty-four women underwent follicular stimulation using a flexible GnRH antagonist protocol, and 250 underwent stimulation with a standard long mid-luteal GnRH agonist protocol. Implantation rates (35.9% in the GnRH antagonist group and 29.6% in the GnRH agonist group, P = 0.5) and ongoing pregnancy rates (32.8% in the GnRH antagonist group and 28.8% in the GnRH agonist group, P = 0.5) were equivalent in both groups. The duration of stimulation (9.8 ± 2 days vs. 10.7 ± 1.8 days, P < 0.001) and total FSH dose required (2044 vs. 2775 IU, P < 0.001) were lower in the GnRH antagonist group than in the GnRH agonist group. The number of mature oocytes (6.0 vs. 10.0, P < 0. 001) and number of embryos (5.0 vs. 7.0, P < 0.001) were also lower in GnRH antagonist group. However, the number of embryos cryopreserved was similar in both groups (median 2.0, P = 0.3). In women undergoing in vitro fertilization, the flexible GnRH antagonist protocol yields implantation and ongoing pregnancy rates that are similar to the long GnRH agonist protocol, and requires lower doses of gonadotropins and a shorter duration of treatment. The flexible GnRH antagonist protocol appears to be the protocol of choice for an eSET IVF program.

Suppression of meiosis of male germ cells by an antagonist of luteinizing hormone-releasing hormone.

PubMed Central

Szende, B; Redding, T W; Schally, A V

1990-01-01

Male nude mice were implanted with osmotic minipumps releasing 50 micrograms of a potent antagonist of luteinizing hormone-releasing hormone (LH-RH) per day [N-Ac-[D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH] (SB-75) [Nal(2), 3-(2-naphthyl)alanine; Phe(pCl), 4-chlorophenylalanine; Pal(3), 3-(3-pyridyl)alanine; Cit, citrulline], or they were treated with s.c. injections of SB-75 (25 micrograms twice a day). Another group of nude mice received an injection of microcapsules of the agonist [D-Trp6]LH-RH liberating 25 micrograms/day. One month after the initiation of treatment, the testicular weights were significantly reduced and the blood testosterone values were at castration levels in all treated groups. Histologically, only the testicles of the mice treated with SB-75 released from minipumps showed a significant decrease of meiosis. The most advanced forms of germ cells were spermatogonia in 26%, spermatocytes in 17%, and round spermatids in 35% of the seminiferous tubules. Only 22% of the tubules contained elongated spermatids. The suppression of meiotic activity by this modern LH-RH antagonist can possibly be used for the development of methods for male contraception and for the protection of germ cells against the damage caused by cytotoxic drugs and x-radiation. Images PMID:2405399

Mobilization of circulating progenitor cells in multiple myeloma during VCAD therapy with or without rhG-CSF.

PubMed

Majolino, I; Marcenò, R; Buscemi, F; Scimè, R; Vasta, S; Indovina, A; Pampinella, M; Catania, P; Santoro, A

1995-01-01

Circulating progenitor cells (CPC), when infused in large numbers, rapidly repopulate the marrow after myeloablation with high-dose therapy. In multiple myeloma (MM), as in other disorders, different chemotherapy regimens, including single-as well as multiple-agent chemotherapy, with or without hemopoietic growth factors, have been proposed to mobilize these progenitor cells into the blood. Here we report our experience with a drug combination called VCAD and compare the results to those obtained by adding rhG-CSF to the same combination. Fourteen MM patients were given one course of VCAD, a chemotherapy association of vincristine 2 mg, cyclophosphamide 4 x 0.5 g/m2, adriamycin 2 x 50 mg/m2 and dexamethasone 4 x 40 mg, before undergoing apheresis to collect CPC for autografting. Seven also received rhG-CSF (filgrastim) 5 mcg/kg/day over the period of apheresis. These latter were allocated to rhG-CSF treatment sequentially from the time the drug became available for clinical use. Following VCAD-induced pancytopenia, CFU-GM peaked at a median of 853/mL (range 96-4352; 7.6 times basal level). RhG-CSF administration increased CFU-GM levels but not significantly. With rhG-CSF the CFU-GM peak was reached sooner, toxicity was reduced and granulocytopenia less protracted. Fewer aphereses were run in the rhG-CSF group, there were higher yields per single run, and patients began and completed their collection program more quickly. The VCAD association is able to mobilize CPC in patients with MM, and rhG-CSF is recommended as a fundamental part of the priming schedule.

Phenotypic and allelic distribution of the ABO and Rhesus (D) blood groups in the Cameroonian population.

PubMed

Ndoula, S T; Noubiap, J J N; Nansseu, J R N; Wonkam, A

2014-06-01

Data on blood group phenotypes are important for blood transfusion programs, for disease association and population genetics studies. This study aimed at reporting the phenotypic and allelic distribution of ABO and Rhesus (Rh) groups in various ethnolinguistic groups in the Cameroonians. We obtained ABO and Rhesus blood groups and self-identified ethnicity from 14,546 Cameroonian students. Ethnicity was classified in seven major ethnolinguistic groups: Afro-Asiatic, Nilo-Saharan, Niger-Kordofanian/West Atlantic, Niger-Kordofanian/Adamawa-Ubangui, Niger-Kordofanian/Benue-Congo/Bantu/Grassfield, Niger-Kordofanian/Benue-Congo/Bantu/Mbam and Niger-Kordofanian/Benue-Congo/Bantu/Equatorial. ABO allelic frequencies were determined using the Bernstein method. Differences in phenotypic distribution of blood groups were assessed using the chi-square test; a P value <0.05 being considered as statistically significant. The frequencies of the antigens of blood groups O, A, B and AB were 48.62%, 25.07%, 21.86% and 4.45%, respectively. Rhesus-positive was 96.32%. The allelic frequencies of O, A and B genes were 0.6978, 0.1605 and 0.1416, respectively. Phenotypic frequencies of the blood groups in the general study population and in the different ethnolinguistic groups were in agreement with Hardy-Weinberg equilibrium expectations (P > 0.05). The frequencies of O, A, and B blood phenotypes were significantly lower, respectively, in the Nilo-Saharan group (P = 0.009), the Niger-Kordofanian/Benue-Congo/Bantu groups (P = 0.021) and the Niger-Kordofanian/West-Atlantic group. AB blood group was most frequent in the Niger-Kordofanian/Adamawa-Ubangui group (P = 0.024). Our study provides the first data on ethnic distribution of ABO and Rhesus blood groups in the Cameroonian population and suggests that its general profile is similar to those of several sub-Saharan African populations. We found some significant differences in phenotypic distribution amongst major ethnolinguistic groups. These data may be important for blood donor recruitment policy and blood transfusion service in Cameroon. © 2014 John Wiley & Sons Ltd.

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO)

PubMed Central

Khan, Khalid S.; Wilson, Matthew J.; Hooper, Richard; Allard, Shubha; Wrench, Ian; Geoghegan, James; Catling, Sue; Clark, Vicki A.; Ayuk, Paul; Robson, Stephen; Gao-Smith, Fang; Hogg, Matthew; Dodds, Julie

2017-01-01

Background Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. Methods and findings We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference −1.03, 95% CI −2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. Conclusions The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. Trial registration This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656. PMID:29261655

Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor.

PubMed

Cavallaro, A M; Lilleby, K; Majolino, I; Storb, R; Appelbaum, F R; Rowley, S D; Bensinger, W I

2000-01-01

One hundred and one donors who had received filgrastim (rhG-CSF) for the purpose of donating either granulocytes or peripheral blood stem cells (PBSC) for their relatives more than 3 years ago were contacted. All donors had received daily rhG-CSF at a median dose of 16 microg/kg/day (range 3-16) for a median of 6 days (range 3-15 days). All collection procedures were completed and short-term side-effects of rhG-CSF were mild in the majority of the donors. At a median time interval of 43.13 months (range 35-73), the donors were contacted to assess whether adverse effects related to rhG-CSF administration had occurred. Prior to rhG-CSF two donors had cancer, one had a myocardial infarction, one was hepatitis C virus positive, one had a history of sinusitis, one had Graves' disease and two had arterial hypertension. None worsened with the rhG-CSF administration but the donor with a history of infarction had an episode of angina following apheresis, and the donor with Graves' disease had a stroke 15 months after rhG-CSF. Two pregnancies occurred after the rhG-CSF administration and one donor was 2-3 weeks pregnant during rhG-CSF treatment. Three pregnancies resulted in two normal births and one in a spontaneous abortion of a pregnancy which occurred more than 2 years following rhG-CSF. In the time following rhG-CSF administration two donors developed cancer (breast and prostate cancer) at a follow-up of 70 and 11 months, respectively. One donor developed lymphadenopathy 38 months after the rhG-CSF, which spontaneously resolved. Blood counts were obtained in 70 donors at a median follow up of 40.4 months (range 16.8-70.8). Hematocrit was 43% (median, range 36.8-48), white blood cells were 5.7 x 109/l (median, range 3-14), granulocytes 3.71 x 109/l (median, range 1. 47-10.36), lymphocytes 1.67 x 109/l (median, range 0.90-3.96), monocytes 0.46 x 109/l (median, range 0.07-0.87) and platelet counts were 193.0 x 109/l (median, range 175.0-240.0). This study indicates that short-term administration of rhG-CSF to normal donors for the purpose of mobilizing the PBSC or granulocytes appears safe and without any obvious adverse effects more than 3 years after the donation. Bone Marrow Transplantation (2000) 25, 85-89.

[Assessment of resistant hypertension with home blood pressure monitoring].

PubMed

Marui, Fabiane Rosa Rezende H; Bombig, Maria Teresa Nogueira; Francisco, Yoná Afonso; Thalenberg, José Marcos; Fonseca, Francisco Antonio Helfenstein; Souza, Dilma de; Costa, Francisco de Assis; Izar, Maria Cristina; Carvalho, Antonio Carlos de Camargo; Póvoa, Rui

2010-10-01

ambulatory blood pressure monitoring (ABPM) is considered the gold standard for the diagnostic confirmation of resistant hypertension (RH). However, home blood pressure monitoring (HBPM) has been considered an option, because of its lower cost and greater comfort. to compare the values obtained by HBPM with those obtained by ABPM in the identification of patients with resistant hypertension. a total of 51 consecutive patients with resistant hypertension were selected. All were adults of both genders and were undergoing treatment in an outpatient referral clinic from January 2007 to September 2009. Casual office blood pressure (BP), 24-hour ABPM, and HBPM were performed according to current guidelines, with a maximum two-week interval between the methods. the comparison of ABPM (mean daytime) with HBPM showed a good correlation between them, both for systolic blood pressure (SBP) and for diastolic blood pressure (DBP): SBP r = 0.70, CI = 0.51-0.82, DBP r = 0.69, CI = 0.52-0.81. RH was confirmed by ABPM in 33 patients and by HBPM in 37, with no significant difference between the methods. according to the results obtained, we conclude that HBPM is a method that can be used as an alternative to ABPM for the diagnostic confirmation of RH.

A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

PubMed Central

Douglas, Alexander D.; Baldeviano, G. Christian; Lucas, Carmen M.; Lugo-Roman, Luis A.; Crosnier, Cécile; Bartholdson, S. Josefin; Diouf, Ababacar; Miura, Kazutoyo; Lambert, Lynn E.; Ventocilla, Julio A.; Leiva, Karina P.; Milne, Kathryn H.; Illingworth, Joseph J.; Spencer, Alexandra J.; Hjerrild, Kathryn A.; Alanine, Daniel G.W.; Turner, Alison V.; Moorhead, Jeromy T.; Edgel, Kimberly A.; Wu, Yimin; Long, Carole A.; Wright, Gavin J.; Lescano, Andrés G.; Draper, Simon J.

2015-01-01

Summary Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans. PMID:25590760

Effects of rhG-CSF (filgrastim) on the recovery of hematopoiesis after high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children: a report from the Children's Cancer and Leukemia Study Group of Japan.

PubMed

Suzue, T; Takaue, Y; Watanabe, A; Kawano, Y; Watanabe, T; Abe, T; Kuroda, Y; Matsushita, T; Kikuta, A; Iwai, A

1994-11-01

In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT). Fifty-three patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) therapy after PBSCT, and the data were compared by actuarial analysis to those of 45 historic controls. The number of days required to achieve a white blood cell count (WBC) of 1 x 10(9)/L, an absolute granulocyte count (AGC) of 5 x 10(8)/L, and a platelet count (PLT) of 5 x 10(10)/L were, respectively, 12.8 +/- 6.4 (mean +/- standard deviation [SD]), 13.4 +/- 6.4, and 49.2 +/- 78.2 in treated patients vs. 12.8 +/- 4.6, 14.4 +/- 10.3, and 31.4 +/- 38.8 days in historic controls, with no significant differences. There was no significant difference between the average number of days with fever in the treated group (6.0 +/- 6.6) and that in the control group (4.0 +/- 2.8). All febrile episodes responded promptly and successfully to parenteral antibiotic therapy. Thus, the data may suggest the possibility that therapy with filgrastim has only a limited ability to enhance hematopoietic recovery after PBSCT. To confirm this notion, we initiated a prospective randomized trial by recruiting a larger number of patients.

The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

PubMed

Ozcan Cenksoy, Pinar; Ficicioglu, Cem; Kizilkale, Ozge; Suhha Bostanci, Mehmet; Bakacak, Murat; Yesiladali, Mert; Kaspar, Cigdem

2014-07-01

To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p=0.002) and serum E2 levels on the day of hCG administration (p=0.010) were significantly higher and duration of stimulations (p=0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p=0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.

Long-Term Safety of Short-Term Administration of Filgrastim (rhG-CSF) and Leukophresis Procedure in Healthy Children: Application of Peripheral Blood Stem Cell Collection in Pediatric Donors.

PubMed

Behfar, Maryam; Faghihi-Kashani, Sara; Hosseini, Ashraf Sadat; Ghavamzadeh, Ardeshir; Hamidieh, Amir Ali

2018-04-01

Administration of filgrastim (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) (Neupogen) in healthy donors to mobilize hematopoietic stem cells (HSCs) is a widespread practice in adults. Application of peripheral blood stem cell (PBSC) collection in normal pediatric donors is scarce due to ethical issues. Hence, there are insufficient data on the long-term impact of PBSC procedure in healthy children. This retrospective study aimed to evaluate the early and late adverse effects of PBSC donation in pediatric donors. Bone marrow and PBSC procedures and known adverse events of each technique were completely explained to parents and when applicable to children and written informed consent was obtained. rhG-CSF was administered for 4 days. HSCs were collected on the fifth day through continuous-flow apheresis and donors were followed for 30 days. Manual chart review was performed to collect short-term complications. Donors' health status was assessed via a questionnaire. A total of 145 healthy pediatric donors with a median age of 10 years at the time of donation (2 to 15 years) were followed for a median of 4.8 years (range, 1.2 to 14.2 years). The most frequent symptoms of rhG-CSF administration were fatigue (5%) and headache (3%). Thirty-five (24%) donors experienced hypocalcaemia during apheresis procedure that quickly responded to treatment. Two pregnancies occurred after rhG-CSF administration that resulted in normal births. We did not encounter any serious adverse events, including neoplastic disorders and death in this study. rhG-CSF and leukophresis procedure were well-tolerated in this study and all children completed the donation process without interruption or reduction of rhG-CSF dosage. Our results suggest that rhG-CSF is a safe drug in healthy children for the purpose of HSC mobilization. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Effects of nutritional restriction on metabolic, endocrine, and ovarian function in llamas (Lama glama).

PubMed

Norambuena, M C; Silva, M; Urra, F; Ulloa-Leal, C; Fernández, A; Adams, G P; Huanca, W; Ratto, M H

2013-05-01

The objectives of the study were to determine the effects of nutritional restriction on ovarian function in llamas. Mature female llamas were assigned randomly to a Control group, fed 100% of maintenance energy requirements (MER) (n=8), or a Restricted group (n=8) fed from 70% to 40% of MER until a body condition score of 2.5 was attained. Blood samples were taken every-other-day to determine plasma concentrations of LH, estradiol, leptin and metabolic markers, and follicular dynamics were monitored daily by ultrasonography for 30 days (Experiment 1). Llamas were then treated with GnRH to compare the ovulatory response and corpus luteus (CL) development between groups (Experiment 2). Blood samples were taken to measure LH, leptin, progesterone and metabolic markers and ovarian structures were assessed as in Experiment 1. Llamas in the Restricted group had lower body mass and body condition scores than those in the Control group (P<0.001). Plasma concentrations of cholesterol, non-esterified fatty acids, triglycerides, and urea were higher in the Restricted group (P<0.05) than in the Control group. The day-to-day diameter profiles of the dominant follicles were smaller (P<0.05) in the Restricted group than in the Control group but plasma estradiol concentration did not differ. The ovulation rate and LH secretion in response to GnRH did not differ. Day-to-day profiles of CL diameter, plasma progesterone and leptin concentrations were smaller (P<0.01) in the Restricted group. In conclusion, nutritional restriction in llamas was associated with suppressed follicle and CL development, and lower plasma concentrations of progesterone and leptin. Copyright © 2013 Elsevier B.V. All rights reserved.

Protective effects of recombinant human brain natriuretic peptide against LPS-Induced acute lung injury in dogs.

PubMed

Song, Zhi; Cui, Yan; Ding, Mu-Zi; Jin, Hong-Xu; Gao, Yan

2013-11-01

Acute lung injury (ALI) is a common component of systemic inflammatory disease without more effective treatments. However, recent studies have demonstrated that the recombinant human brain natriuretic peptide (rhBNP) has anti-inflammatory effects. Therefore, we found that rhBNP could prevent lipopolysaccharide (LPS)-induced acute lung injury in a dog model. Dogs were injected with LPS and subjected to continuous intravenous infusion (CIV) of saline solution or rhBNP. We detected the protective effects of rhBNP by histological examination and determination of serum cytokine levels and lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) activity. Histological examination indicated marked inflammation, edema and hemorrhage in lung tissue taken 12h after rhBNP treatment compared with tissue from dogs which received saline treatment after LPS injection. LPS injection induced cytokine (IL-6 and TNF-α) secretion and lung MPO and MDA activities, which were also attenuated by rhBNP treatment. Inductions of IL-6 and TNF-α were significantly attenuated in the L-rhBNP and the H-rhBNP groups. The ratios of the L-rhBNP group and H-rhBNP group were lower than that in the lung injury group. Furthermore, MPO and MDA activities were significantly lower in the H-rhBNP group compared to those in the LI group. Our data indicate that rhBNP treatment may exert protective effects and may be associated with adjusting endogenous antioxidant enzymes. Thus, rhBNP may be considered as a therapeutic agent for various clinical conditions involving lung injury by sepsis. Copyright © 2013 Elsevier B.V. All rights reserved.

Physiological and subjective responses to low relative humidity.

PubMed

Sunwoo, Yujin; Chou, Chinmei; Takeshita, Junko; Murakami, Motoko; Tochihara, Yutaka

2006-01-01

In order to investigate the influence of low relative humidity, we measured saccharin clearance time (SCT), frequency of blinking, heart rate (HR), blood pressure, hydration state of skin, transepidermal water loss (TEWL), recovery sebum level and skin temperature as physiological responses. We asked subjects to judge thermal, dryness and comfort sensations as subjective responses using a rating scale. Sixteen non-smoking healthy male students were selected. The pre-room conditions were maintained at an air temperature (Ta) of 25 degrees C and a relative humidity (RH) of 50%. The test room conditions were adjusted to provide a Ta of 25 degrees C and RH levels of 10%, 30% and 50%.RH had no effect on the activity of the sebaceous gland and on cardiovascular reactions like blood pressure and HR. However, it was obvious that low RH affects SCT, the dryness of the ocular mucosa and the stratum corneum of the skin and causes a decrease in mean skin temperature. Under 30% RH, the eyes and skin become dry, and under 10% RH the nasal mucous membrane becomes dry as well as the eyes and skin, and the mean skin temperature decreases. These findings suggested that to avoid dryness of the eyes and skin, it is necessary to maintain an RH greater than 30%, and to avoid dryness of the nasal mucous membrane, it is necessary to maintain an RH greater than 10%. Subjects felt cold immediately after a change in RH while they had only a slight perception of dryness at the change of humidity.

Oral administration of erythrocyte membrane antigen does not suppress anti-Rh(D) antibody responses in humans.

PubMed Central

Barnes, R M; Duguid, J K; Roberts, F M; Risk, J M; Johnson, P M; Finn, R; Hardy, J; Napier, J A; Clarke, C A

1987-01-01

The effects of prior oral administration of erythrocyte membrane preparations (Oral Rh antigen) on the serum anti-Rh(D) antibody response has been evaluated in non-sensitized Rh(D)-negative male volunteers, and in female volunteers sensitized previously by Rh(D)-positive fetal blood during pregnancy. Sixty-one percent (11/18) of males who received oral Rh antigen (either D-positive or D-negative) before intravenous challenge with Rh(D)-positive cells produced detectable antibodies; of these 11, six received oral Rh(D)-negative antigen and five received oral Rh(D)-positive antigen. Seventy-two percent (13/18) of control males, who had received no prior oral Rh antigen, produced antibodies following challenge with Rh(D)-positive cells. Three out of six pre-sensitized females who received oral D-positive or D-negative Rh antigen for 4 weeks, but without intravenous challenge, increased their anti-Rh(D) antibody levels which peaked after 11-18 weeks: two had received Rh(D)-positive antigen, and one Rh(D)-negative antigen. These data indicate that administration of oral Rh antigen before parenteral immunization does not significantly suppress the anti-Rh(D) antibody response. Indeed, oral administration of either Rh(D)-positive or Rh(D)-negative antigen can boost systemic antibody in pre-sensitized females. These results do not support the rationale of treating Rh-sensitized pregnant women with oral Rh antigen. PMID:3113783

Exchange transfusion

MedlinePlus

... with donor blood. In conditions such as neonatal polycythemia , a specific amount of the child's blood is ... red blood cell count in a newborn (neonatal polycythemia) Rh-induced hemolytic disease of the newborn Severe ...

Acoustic radiation force impulse elastosonography of placenta in maternal red blood cell alloimmunization: a preliminary and descriptive study.

PubMed

Cetin, Orkun; Karaman, Erbil; Arslan, Harun; Akbudak, Ibrahim; Yıldızhan, Recep; Kolusarı, Ali

2017-01-31

Maternal red blood cell alloimmunization is an important cause of fetal morbidity and mortality in the perinatal period, despite well-organized prophylaxis programs. The objective of the study was to evaluate placental elasticity by using Acoustic Radiation Force Impulse (ARFI) in Rhesus (Rh) alloimmunized pregnant women with hydropic and nonhydropic fetuses and to compare those with healthy pregnant women. This case-control and descriptive study comprised twenty-eight healthy pregnant women, 14 Rh alloimmunized pregnant women with nonhydropic fetuses, and 16 Rh alloimmunized pregnant women with hydropic fetuses in the third trimester of pregnancy. Placental elasticity measurements were performed by ARFI elastosonography at the day of delivery. The maternal characteristics and neonatal outcomes of the patients were also noted. The highest mean placental ARFI scores were observed in Rh alloimmunized pregnant women with hydropic fetuses (1.13 m/s) (p=0.001). Healthy controls and Rh alloimmunized pregnant women with nonhydropic fetuses had similar mean placenta ARFI scores (0.84 m/s, 0.88 m/s, respectively) (p<0.05). Based on the present findings, the placenta becomes stiffer in Rh alloimmunized pregnancies complicated with hydrops fetalis. The increased placental ARFI scores may be a supplemental marker for adverse pregnancy outcomes, additional to Doppler evaluation of middle cerebral artery. This data should be confirmed with a large sample size and prospective studies by using serial measurements of ARFI elastosonography in maternal red blood cell alloimmunization.

Comparison of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical-size defects.

PubMed

Nakamura, Toshiaki; Shirakata, Yoshinori; Shinohara, Yukiya; Miron, Richard J; Hasegawa-Nakamura, Kozue; Fujioka-Kobayashi, Masako; Noguchi, Kazuyuki

2017-12-01

Among bone morphogenetic protein (BMP) family members, BMP-2 and BMP-9 have demonstrated potent osteoinductive potential. However, in vivo differences in their potential for bone regeneration remain unclear. The present study aimed to compare the effects of recombinant human (rh) BMP-2 and rhBMP-9 on bone formation in rat calvarial critical-size defects (CSD). Twenty-eight Wistar rats surgically received two calvarial defects bilaterally in each parietal bone. Defects (n = 56) were allocated into four groups: absorbable collagen sponge (ACS) alone, rhBMP-2 with ACS (rhBMP-2/ACS), rhBMP-9/ACS, or sham surgery (control), on the condition that the treatments of rhBMP-2/ACS and rhBMP-9/ACS, or the same treatments were not included in the same animal. Animals were sacrificed at 2 and 8 weeks post-surgery. The calvarial defects were analyzed for bone volume (BV) by micro-computed tomography and for percentages of defect closure (DC/DL), newly formed bone area (NBA/TA), bone marrow area (BMA/NBA), adipose tissue area (ATA/NBA), central bone height (CBH), and marginal bone height (MBH) by histomorphometric analysis. The BV in the rhBMP-2/ACS group (5.44 ± 3.65 mm 3 , n = 7) was greater than the other groups at 2 weeks post-surgery, and the rhBMP-2/ACS and rhBMP-9/ACS groups (18.17 ± 2.51 and 16.30 ± 2.46 mm 3 , n = 7, respectively) demonstrated significantly greater amounts of BV compared with the control and ACS groups (6.02 ± 2.90 and 9.30 ± 2.75 mm 3 , n = 7, respectively) at 8 weeks post-surgery. The rhBMP-2/ACS and rhBMP-9/ACS groups significantly induced new bone formation compared to the control and ACS groups at 8 weeks post-surgery. However, there were no statistically significant differences found between the rhBMP-2/ACS and rhBMP-9/ACS groups in any of the histomorphometric parameters. The ATA/NBA in the rhBMP-2/ACS group (9.24 ± 3.72%, n = 7) was the highest among the treatment groups at 8 weeks post-surgery. Within the limits of this study, it can be concluded that rhBMP-2/ACS induced a slight early increase in new bone formation at 2 weeks and that rhBMP-9/ACS provided comparable new bone formation to rhBMP-2/ACS with less adipose tissues after a healing period of 8 weeks in rat CSD. RhBMP-9/ACS treatment provided new bone formation with less adipose tissues compared with rhBMP-2/ACS.

In vivo investigations of the effect of short- and long-term recombinant growth hormone treatment on DNA-methylation in humans.

PubMed

Kolarova, Julia; Ammerpohl, Ole; Gutwein, Jana; Welzel, Maik; Baus, Inka; Riepe, Felix G; Eggermann, Thomas; Caliebe, Almuth; Holterhus, Paul-Martin; Siebert, Reiner; Bens, Susanne

2015-01-01

Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation. We performed array-based DNA-methylation profiling of paired peripheral blood mononuclear cell samples followed by targeted validation using bisulfite pyrosequencing. Unsupervised analysis of DNA-methylation in this short-term treated cohort revealed clustering according to individuals rather than treatment. Supervised analysis identified 239 CpGs as significantly differentially methylated between baseline and rhGH-stimulated samples (p<0.0001, unadjusted paired t-test), which nevertheless did not retain significance after adjustment for multiple testing. An individualized evaluation strategy led to the identification of 2350 CpG and 3 CpH sites showing methylation differences of at least 10% in more than 2 of the 24 analyzed sample pairs. To investigate the long term effects of rhGH treatment on the DNA-methylome, we analyzed peripheral blood cells from an independent cohort of 36 rhGH treated children born small for gestational age (SGA) as compared to 18 untreated controls. Median treatment interval was 33 months. In line with the groupwise comparison in the short-term treated cohort no differentially methylated targets reached the level of significance in the long-term treated cohort. We identified marked intra-individual responses of DNA-methylation to short-term rhGH treatment. These responses seem to be predominately associated with immunologic functions and show considerable inter-individual heterogeneity. The latter is likely the cause for the lack of a rhGH induced homogeneous DNA-methylation signature after short- and long-term treatment, which nevertheless is well in line with generally assumed safety of rhGH treatment.

Fabrication of Vascularized Bone Flaps with Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 and Arteriovenous Bundle.

PubMed

Li, Bo; Ruan, Changshun; Ma, Yufei; Huang, Zhifeng; Huang, Zhenfei; Zhou, Gang; Zhang, Jing; Wang, Hai; Wu, Zhihong; Qiu, Guixing

2018-05-21

It is a common treatment strategy in the clinic to transplant a vascularized bone flap for a large bone defect. But it is difficult for peripheral blood vessels to grow into the central region of a large bone construct. In this study, we fabricated a vascularized bone flap from a three-dimensional (3D)-printed biodegradable poly(lactide-co-glycolide) (PLGA)/β-tri-calcium phosphate (β-TCP) scaffold using the combination of an arteriovenous (AV) bundle and recombinant human bone morphogenetic protein-2 (rhBMP-2). A degradable porous PLGA/β-TCP scaffold was prepared by adopting 3D plotting and a low-temperature deposition technique. rhBMP-2 chitosan microspheres (CMs) were fabricated and loaded into the scaffolds to induce ectopic bone formation. In Group SBV (scaffold+rhBMP-2+vessel), a femoral AV bundle was implanted into the central tunnel of the composite before embedding into intramuscular pockets. In Group SB (scaffold+rhBMP-2), the composite was directly implanted into intramuscular pockets. Bone formation was evaluated by imaging analysis (X-rays and microcomputed tomography) and histological analysis (Hematoxylin and Eosin staining and Masson staining) after 4 and 12 weeks, respectively. Vascularization was also assessed by imaging analysis (Microfil angiography) and histological analysis (CD31 immunohistochemical staining). The 3D-printed PLGA/β-TCP scaffold had good cytocompatibility. Ectopic bone formation in the scaffold could be successfully induced by the controlled release of rhBMP-2 through CMs. Comparing groups SBV and SB, vascularization of the composite was significantly enhanced by AV bundle implantation at 4 and 12 weeks. Moreover, rhBMP-2-induced bone formation was also significantly improved by the AV bundle at 4 and 12 weeks. The AV bundle not only improved vascularization and bone formation of the construct, but also provided a defined vascular axis to connect with the vascular system of the bone defect by microsurgical techniques. It provided a new potential treatment strategy to repair large bone defects, especially for those with low vascular supply.

Molecular Diagnostics in Transfusion Medicine: In Capillary, on a Chip, in Silico, or in Flight?

PubMed Central

Garritsen, Henk S.P.; Xiu-Cheng Fan, Alex; Lenz, Daniela; Hannig, Horst; Yan Zhong, Xiao; Geffers, Robert; Lindenmaier, Werner; Dittmar, Kurt E.J.; Wörmann, Bernhard

2009-01-01

Summary Serology, defined as antibody-based diagnostics, has been regarded as the diagnostic gold standard in transfusion medicine. Nowadays however the impact of molecular diagnostics in transfusion medicine is rapidly growing. Molecular diagnostics can improve tissue typing (HLA typing), increase safety of blood products (NAT testing of infectious diseases), and enable blood group typing in difficult situations (after transfusion of blood products or prenatal non-invasive RhD typing). Most of the molecular testing involves the determination of the presence of single nucleotide polymorphisms (SNPs). Antigens (e.g. blood group antigens) mostly result from single nucleotide differences in critical positions. However, most blood group systems cannot be determined by looking at a single SNP. To identify members of a blood group system a number of critical SNPs have to be taken into account. The platforms which are currently used to perform molecular diagnostics are mostly gel-based, requiring time-consuming multiple manual steps. To implement molecular methods in transfusion medicine in the future the development of higher-throughput SNP genotyping non-gel-based platforms which allow a rapid, cost-effective screening are essential. Because of its potential for automation, high throughput and cost effectiveness the special focus of this paper is a relative new technique: SNP genotyping by MALDI-TOF MS analysis. PMID:21113259

Short-term administration of rhGH increases markers of cellular proliferation but not milk protein gene expression in normal lactating women

PubMed Central

Maningat, Patricia D.; Sen, Partha; Rijnkels, Monique; Hadsell, Darryl L.; Bray, Molly S.

2011-01-01

Growth hormone is one of few pharmacologic agents known to augment milk production in humans. We hypothesized that recombinant human GH (rhGH) increases the expression of cell proliferation and milk protein synthesis genes. Sequential milk and blood samples collected over four days were obtained from five normal lactating women. Following 24 h of baseline milk and blood sampling, rhGH (0.1 mg/kg/day) was administered subcutaneously once daily for 3 days. Gene expression changes were determined by microarray studies utilizing milk fat globule RNA isolated from each milk sample. Following rhGH administration, DNA synthesis and cell cycle genes were induced, while no significant changes were observed in the expression of milk synthesis genes. Expression of glycolysis and citric acid cycle genes were increased by day 4 compared with day 1, while lipid synthesis genes displayed a circadian-like pattern. Cell cycle gene upregulation occurred after a lag of ∼2 days, likely explaining the failure to increase milk production after only 3 days of rhGH treatment. We conclude that rhGH induces expression of cellular proliferation and metabolism genes but does not induce milk protein gene expression, as potential mechanisms for increasing milk production and could account for the known effect of rhGH to increase milk production following 7–10 days. PMID:21205870

Recombinant human granulocyte colony-stimulating factor after kidney transplantation: a retrospective analysis to evaluate the benefit or risk of immunostimulation.

PubMed

Schmaldienst, S; Bekesi, G; Deicher, R; Franz, M; Hörl, W H; Pohanka, E

2000-02-27

Leukopenia due to immunosuppressive drugs represents a well-known complication in graft recipients, which might put patients at an increased risk for infections. In this study, recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that selectively stimulates neutrophil colony formation and neutrophil cell differentiation, was tested for safety and efficacy. We evaluated 30 episodes of leukopenia (<2000/mm3) in 19 kidney graft recipients treated with rhG-CSF. This cohort was compared with an age- and sex-matched historical control group without therapy. Peripheral and differential blood cell counts were analyzed, and the duration of leukopenia was estimated. Furthermore, the occurrence of infections associated with leukopenia was investigated. All patients responded to rhG-CSF therapy. Peripheral leukocyte counts increased from 1756+/-582 to a peak of 8723+/-3038/mm3 (P<0.0001). On the average, the peak was reached after 2.7 days (range 1 to 8). Furthermore, the effect was fairly persistent, because in 22 of 30 episodes leukocyte counts were within the normal range after 7 days. The elevation of total leukocytes was mainly due to a specific increase in neutrophil granulocytes from 1143+/-514 to 6895+/-1950/mm3 on the peak day (P<0.0001). Patients in the G-CSF group were leukopenic for a mean of 1.29+/-0.59 days, whereas in the control group leukopenia persisted for at least 7 days. Consequently, the rate of infections was significantly higher (P<0.045) in nontreated patients. rhG-CSF was safe and effective in leukopenic kidney graft recipients. Leukopenic episodes in treated patients were significantly shorter, and infections occurred at a significantly lower rate. No evidence was found that rhG-CSF therapy might trigger rejection episodes, and no side effects were observed.

Identification of gonadotropin-releasing hormone metabolites in greyhound urine.

PubMed

Palmer, David; Rademaker, Katie; Martin, Ingrid; Hessell, Joan; Howitt, Rob

2017-10-01

Gonadotropin-releasing hormone (GnRH) is a 10-residue peptide hormone that induces secretion of luteinizing hormone (LH) and follicle-stimulating hormone into the blood from the pituitary gland. In males, LH acts on the testes to produce testosterone. The performance-enhancing potential of testosterone makes administration of exogenous GnRH a concern in sports doping control. Detection of GnRH abuse is challenging owing to its rapid clearance from the body and its degradation in urine. Following recent investigations of GnRH abuse in racing greyhounds in New Zealand, we carried out a GnRH administration study in greyhounds in an attempt to identify GnRH metabolites that might provide more facile detection of GnRH abuse; little information is available on in vivo metabolites of exogenous GnRH in any species and none in dogs. We identified three C-terminal GnRH metabolites in urine: GnRH 5-10, GnRH 6-10, and GnRH 7-10. These metabolites and intact GnRH, which was also detected in urine, were all excreted over a 1-3 h period after GnRH administration. Two of the GnRH metabolites - GnRH 5-10 and GnRH 6-10 - were more stable in urine than intact GnRH offering improved potential to detect GnRH administration. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Rh Incompatibility (For Parents)

MedlinePlus

... danger, a series of special blood transfusions called exchange transfusions can be done either before the baby is born (intrauterine fetal transfusions) or after delivery. Exchange transfusions replace the baby's blood with blood with ...

Anti-Rh(c), "little c," isoimmunization: the role of rHuEpo in preventing late anemia.

PubMed

Zuppa, Antonio A; Cardiello, Valentina; Alighieri, Giovanni; Cota, Francesco; D'Antuono, Annamaria; Riccardi, Riccardo; Catenazzi, Piero; Romagnoli, Costantino

2013-08-01

The overall prevalence of non-Rh-D isoimmunization seems to lie between 0.15% and 1.1%. Anti-Rh(c) alloimmunization, "little c," occurs in 0.07% of pregnancies and shows a quite broad clinical presentation. Late anemia is a frequent problem occurring in the setting of isoimmunization. It occurs more frequently after intrauterine blood transfusions or exsanguinotransfusion, and it can be thought as a hyporegenerative anemia. The authors describe the use of human recombinant erythropoietin in preventing late anemia in a case of anti-Rh(c) isoimmunization. The use of human recombinant erythropoietin is a valid tool for preventing late-onset anemia due to either anti-Rh-D or non-anti-Rh-D isoimmunization.

Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female.

PubMed

Sarma, Hirendra N; Manikkam, Mohan; Herkimer, Carol; Dell'Orco, James; Welch, Kathleen B; Foster, Douglas L; Padmanabhan, Vasantha

2005-10-01

Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.

Effect of GnRH treatment on ovarian activity and reproductive performance of low-prolific Rahmani ewes.

PubMed

Hashem, N M; El-Azrak, K M; Nour El-Din, A N M; Taha, T A; Salem, M H

2015-01-15

This study was designed to evaluate the effect of GnRH treatment during different times of the reproductive cycle on ovarian activity, progesterone (P4) concentration, and subsequent fertility of low-prolific, subtropical, Rahmani ewes during breeding season. Forty-five ewes were synchronized for estrus using a double injection of 0.5 mL of PGF2α agonist (125-μg cloprostenol), 11 days apart. Ewes showing estrus (Day 0) were treated with 1 mL of GnRH agonist (4-μg buserelin) on the day of estrus (GnRH0, n = 12) or 7 days post-mating (GnRH7, n = 10) or on both days (GnRH0+7, n = 11) or not (control, n = 12). Ovarian response to the treatment and diagnosis of pregnancy were ultrasonographically monitored. Also, serum P4 concentration was determined weekly throughout 28 days post-mating. Results showed that neither total number of follicles nor their populations were changed on Day 0 or 7 days post-mating by the GnRH treatment. GnRH treatment on Day 0 or Day 7 post-mating or both days did not enhance ovulation rate compared with the control. The mean numbers of accessory CL increased (P < 0.05) in the GnRH7 group than those in the control and GnRH0 groups, whereas it was intermediate in the GnRH0+7 group. The greatest (P < 0.05) overall mean of serum P4 concentration was for the GnRH7 and GnRH0+7 groups, followed by the GnRH0 and control groups. Serum P4 concentration increased (P < 0.05) on Day 14 post-mating and continued higher (P < 0.05) until Day 28 post-mating in the GnRH7 and GnRH0+7 groups compared with the control. Regardless of the time of GnRH administration, GnRH treatment reduced (P < 0.05) pregnancy loss from Day 40 post-mating to parturition and tended to enhance (P < 0.20) lambing rate compared with the control. In conclusion, a single dose of GnRH at the time of estrus or 7 days post-mating could be used as an effective protocol to decrease pregnancy loss from Day 40 after mating to parturition in low-prolific Rahmani ewes. Copyright © 2015 Elsevier Inc. All rights reserved.

Allogeneic umbilical cord blood red cell concentrates: an innovative blood product for transfusion therapy of preterm infants.

PubMed

Bianchi, Maria; Giannantonio, Carmen; Spartano, Serena; Fioretti, Maria; Landini, Alessandra; Molisso, Anna; Tesfagabir, Ghennet Mikael; Tornesello, Assunta; Barbagallo, Ombretta; Valentini, Caterina Giovanna; Vento, Giovanni; Zini, Gina; Romagnoli, Costantino; Papacci, Patrizia; Teofili, Luciana

2015-01-01

Preterm infants often receive blood transfusions early in life. In this setting, umbilical cord blood (UCB) might be safer than adult blood (A) with respect to infectious and immunologic threats. To evaluate, as a first objective, the feasibility of fulfilling transfusion needs of preterm infants with allogeneic UCB red blood cell (RBC) concentrates and, as a secondary objective, to assess the safety of allogeneic cord blood transfusions. At the Neonatal Intensive Care Unit and the UNICATT Cord Blood Bank of 'A. Gemelli' Hospital in Rome, a prospective study was carried out over a 1-year period, enrolling newborns with gestational age ≤30 weeks and/or birth weight ≤1,500 g requiring RBC transfusions within the first 28 days of life. At first transfusion, patients were assigned to receive UCB-RBCs or A-RBCs depending on the availability of ABO-Rh(D)-matched UCB-RBC units. The same regimen (UCB-RBC or A-RBC units) was thereafter maintained, unless ABO-Rh(D)-matched UCB-RBC units were not available. Overall, 23 UCB-RBC units were transfused to 9 patients; the requests for UCB-RBC units were met in 45% of patients at the first transfusion and in 78% at the subsequent transfusions. At a median follow-up of 57 days (range 6-219), no acute or delayed transfusion-related adverse events occurred. Hematocrit gain after transfusion and time intervals between transfusions were similar in the UCB-RBC and A-RBC group, as well. Transfusing allogeneic UCB-RBC units in preterm infants appears a feasible and safe approach, although the transfusion needs of our study population were not completely covered. More data are necessary to validate this novel transfusion practice. © 2014 S. Karger AG, Basel.

Fertility of Angus cross beef heifers after GnRH treatment on day 23 and timing of insemination in 14-day CIDR protocol.

PubMed

Kasimanickam, R K; Hall, J B; Whittier, W D

2017-02-01

This study compared artificial insemination pregnancy rate (AI-PR) between 14-day CIDR-GnRH-PGF2α-GnRH and CIDR-PGF2α-GnRH synchronization protocol with two fixed AI times (56 or 72 hr after PGF2α). On day 0, heifers (n = 1311) from nine locations assigned body condition score (BCS: 1, emaciated; 9, obese), reproductive tract score (RTS: 1, immature, acyclic; 5, mature, cyclic) and temperament score (0, calm; and 1, excited) and fitted with a controlled internal drug release (CIDR, 1.38 g of progesterone) insert for 14 days. Within herd, heifers were randomly assigned either to no-GnRH group (n = 635) or to GnRH group (n = 676), and heifers in GnRH group received 100 μg of GnRH (gonadorelin hydrochloride, IM) on day 23. All heifers received 25 mg of PGF2α (dinoprost, IM) on day 30 and oestrous detection aids at the same time. Heifers were observed for oestrus thrice daily until AI. Within GnRH groups, heifers were randomly assigned to either AI-56 or AI-72 groups. Heifers in AI-56 group (n = 667) were inseminated at 56 hr (day 32 PM), and heifers in AI-72 group (n = 644) were inseminated at 72 hr (day 33 AM) after PGF2α administration. All heifers were given 100 μg of GnRH concurrently at the time AI. Controlling for BCS (p < .05), RTS (p < .05), oestrous expression (p < .001), temperament (p < .001) and GnRH treatment by time of insemination (p < .001), the AI-PR differed between GnRH treatment [GnRH (Yes - 60.9% (412/676) vs. No - 55.1% (350/635); p < .05)] and insemination time [AI-56 - 54.6% (364/667) vs. AI-72 - 61.8% (398/644); (p < .01)] groups. The GnRH treatment by AI time interaction influenced AI-PR (GnRH56 - 61.0% (208/341); GnRH72 - 60.9% (204/335); No-GnRH56 - 47.9% (156/326); No-GnRH72 - 62.8% (194/309); p < .001). In conclusion, 14-day CIDR synchronization protocol for FTAI required inclusion of GnRH on day 23 if inseminations were to be performed at 56 hr after PGF2α in order to achieve greater AI-PR. © 2016 Blackwell Verlag GmbH.

MNS, Duffy, and Kell blood groups among the Uygur population of Xinjiang, China.

PubMed

Lin, G Y; Du, X L; Shan, J J; Zhang, Y N; Zhang, Y Q; Wang, Q H

2017-03-15

Human blood groups are a significant resource for patients, leading to a fierce international competition in the screening of rare blood groups. Some rare blood group screening programs have been implemented in western countries and Japan, but not particularly in China. Recently, the genetic background of ABO and Rh blood groups for different ethnic groups or regions in China has been focused on increasingly. However, rare blood groups such as MN, Duffy, Kidd, MNS, and Diego are largely unexplored. No systematic reports exist concerning the polymorphisms and allele frequencies of rare blood groups in China's ethnic minorities such as Uygur and Kazak populations of Xinjiang, unlike those on the Han population. Therefore, this study aimed to investigate the allele frequencies of rare blood groups, namely, MNS, Duffy, Kell, Dombrock, Diego, Kidd, Scianna, Colton, and Lutheran in the Uygur population of Xinjiang Single specific primer-polymerase chain reaction was performed for genotyping and statistical analysis of 9 rare blood groups in 158 Uygur individuals. Allele frequencies were compared with distribution among other ethnic groups. Observed and expected values of genotype frequencies were compared using the chi-square test. Genotype frequencies obeyed the Hardy-Weinberg equilibrium (P > 0.5) and allele frequencies were stable. Of all subjects detected, 4 cases carried the rare phenotype S - s - of MNS blood group (frequency of 0.0253), and 1 case carried the phenotype Jk a-b- (frequency of 0.0063). Frequencies of the four groups, MNS, Duffy, Dombrock, and Diego, in the Uygur population differed from those in other ethnic groups. Gene distribution of the Kell, Kidd, and Colton was similar to that in Tibetan and Han populations, though there were some discrepancies. Gene distribution of Scianna and Lutheran groups showed monomorphism similar to that in Tibetan and Han populations. These findings could contribute to the investigation of the origin, evolution, and hematology of Uygur population of Xinjiang and assist in screening of rare blood groups in ethnic minorities, meeting of clinical blood supply demands, and building of the national rare blood group library.

Incidence of Maternal Rh Immunization by ABO Compatible and Incompatible Pregnancies

PubMed Central

Ascari, W. Q.; Levine, P.; Pollack, W.

1969-01-01

The incidence of maternal Rh immunization in Rh-negative women following a single ABO compatible Rh-positive pregnancy is about 17%. This incidence was determined by following Rh-negative women through two Rh-incompatible pregnancies and analysing their sera for anti-Rh at the time of delivery of their second observed pregnancy. Maternal Rh immunization occurs almost exclusively after delivery; however, antibodies may not be detectable in the absence of further antigenic stimulation. The incidence of maternal Rh immunization when maternal-foetal ABO incompatibility is also present is 9–13% and 17% for group O and non-group O women respectively. This study emphasizes the need to offer Rh-immune prophylaxis to Rh-negative women having Rh-positive infants whether or not ABO incompatibility exists between the mother and infant. PMID:4179167

Improved priming for mobilization of and optimal timing for harvest of peripheral blood stem cells.

PubMed

Knudsen, L M; Gaarsdal, E; Jensen, L; Nielsen, K J; Nikolaisen, K; Johnsen, H E

1996-08-01

The time of stem cell harvest and the mobilization regimen may play important roles in terms of achieving adequate numbers of stem cells by leukapheresis. To optimize the timing of leukapheresis, we have determined simultaneously the number of CD34+ cells in the peripheral blood as well as in the leukapheresis product of 214 apheresis procedures performed in 66 unselected patients with malignant hematologic diseases and solid tumors. A significant correlation between the number of CD34+ cells in peripheral blood and the leukapheresis product (R = 0.8) was found. The presence of more than 20 x 10(3)/ml blood CD34+ cells gave a sufficient yield (> or = 1.0 x 10(6) CD34+ cells/kg) in 81% of the cases. In an attempt to compare two priming regimens, we performed leukapheresis twice in 12 patients with stable disease. In the first sequence, stem cells were mobilized with rhG-CSF (10 micrograms/kg/day) alone and, in the second sequence, with cyclophosphamide (4 g/m2) plus rhG-CSF. A significantly higher yield of CD34+ cells and a better correlation between CD34+ cells in the peripheral blood and the leukapheresis product were found after priming with high-dose cyclophosphamide plus rhG-CSF, compared with priming with rhG-CSF alone. In a multivariate analysis, three factors were found to correlate with the yield of CD34+ cells, namely prior chemotherapy, bone marrow function, and the mobilization regimen. The use of cyclophosphamide priming improves CD34+ mobilization, and the introduction of blood CD34+ level optimizes the timing for harvest of stem cells, which should be performed early during treatment of malignancies.

Complications Related to the Recombinant Human Bone Morphogenetic Protein 2 Use in Posterior Cervical Fusion.

PubMed

Takahashi, Shinji; Buser, Zorica; Cohen, Jeremiah R; Roe, Allison; Myhre, Sue L; Meisel, Hans-Joerg; Brodke, Darrel S; Yoon, S Tim; Park, Jong-Beom; Wang, Jeffrey C; Youssef, Jim A

2017-11-01

A retrospective cohort study. To compare the complications between posterior cervical fusions with and without recombinant human bone morphogenetic protein 2 (rhBMP2). Use of rhBMP2 in anterior cervical spinal fusion procedures can lead to potential complications such as neck edema, resulting in airway complications or neurological compression. However, there are no data on the complications associated with the "off-label" use of rhBMP2 in upper and lower posterior cervical fusion approaches. Patients from the PearlDiver database who had a posterior cervical fusion between 2005 and 2011 were identified. We evaluated complications within 90 days after fusion and data was divided in 2 groups: (1) posterior cervical fusion including upper cervical spine O-C2 (upper group) and (2) posterior cervical fusion including lower cervical spine C3-C7 (lower group). Complications were divided into: any complication, neck-related complications, wound-related complications, and other complications. Of the 352 patients in the upper group, 73 patients (20.7%) received rhBMP2, and 279 patients (79.3%) did not. Likewise, in the lower group of 2372 patients, 378 patients (15.9%) had surgery with rhBMP2 and 1994 patients (84.1%) without. In the upper group, complications were observed in 7 patients (9.6%) with and 34 patients (12%) without rhBMP2. In the lower group, complications were observed in 42 patients (11%) with and 276 patients (14%) without rhBMP2. Furthermore, in the lower group the wound-related complications were significantly higher in the rhBMP2 group (23 patients, 6.1%) compared with the non-rhBMP2 group (75 patients, 3.8%). Our data showed that the use of rhBMP2 does not increase the risk of complications in upper cervical spine fusion procedures. However, in the lower cervical spine, rhBMP2 may elevate the risk of wound-related complications. Overall, there were no major complications associated with the use of rhBMP2 for posterior cervical fusion approaches. Level III.

Evaluation of the pituitary-gonadal response to GnRH, and adrenal status, in the leopard (Panthera pardus japonensis) and tiger (Panthera tigris).

PubMed

Brown, J L; Goodrowe, K L; Simmons, L G; Armstrong, D L; Wildt, D E

1988-01-01

Frequent blood samples were collected to study hormonal responses to GnRH in male and female leopards and tigers. Animals were anaesthetized with ketamine-HCl and blood samples were collected every 5 min for 15 min before and 160 min after i.v. administration of GnRH (1 micrograms/kg body weight) or saline. No differences in serum cortisol concentrations were observed between sexes within species, but mean cortisol was 2-fold greater in leopards than tigers. GnRH induced a rapid rise in LH in all animals (18.3 +/- 0.9 min to peak). Net LH peak height above pretreatment levels was 3-fold greater in males than conspecific females and was also greater in tigers than leopards. Serum FSH increased after GnRH, although the magnitude of response was less than that observed for LH. Basal LH and FSH and GnRH-stimulated FSH concentrations were not influenced by sex or species. Serum testosterone increased within 30-40 min after GnRH in 3/3 leopard and 1/3 tiger males. Basal testosterone was 3-fold greater in tiger than leopard males. LH pulses (1-2 pulses/3 h) were detected in 60% of saline-treated animals, suggesting pulsatile gonadotrophin secretion; however, in males concomitant testosterone pulses were not observed. These results indicate that there are marked sex and species differences in basal and GnRH-stimulated hormonal responses between felids of the genus Panthera which may be related to differences in adrenal activity.

Dynamic response of C-type natriuretic peptide and its aminoterminal propeptide (NTproCNP) to growth hormone treatment in children with short stature.

PubMed

Olney, Robert C; Salehi, Parisa; Prickett, Timothy C R; Lima, John J; Espiner, Eric A; Sikes, Kaitlin M; Geffner, Mitchell E

2016-10-01

C-type natriuretic peptide (CNP) and its aminoterminal propeptide (NTproCNP) are potential biomarkers of recombinant human growth hormone (rhGH) efficacy. The objective of this study was to describe the pharmacodynamics of plasma CNP and NTproCNP levels in response to rhGH treatment and to identify the optimal time of sampling after starting rhGH. This was a prospective, observational study. Subjects were treated with rhGH for 1 year, with blood sampled at regular intervals. Eighteen prepubertal children, eight with low levels of GH on biochemical testing and ten with idiopathic short stature, completed the study. Blood levels of CNP, NTproCNP, GH, insulin-like growth factor-I, leptin and bone-specific alkaline phosphatase were measured. Anthropometrics were obtained. Plasma levels of both CNP and NTproCNP reached peak levels 7-28 days after starting rhGH treatment and then declined to intermediate levels through the first year. Plasma NTproCNP levels after 14 days trended towards a correlation with height velocity after 6 and 12 months of treatment. Unexpectedly, serum GH levels measured 2 and 28 days after starting rhGH correlated strongly with height velocity after 6 and 12 months of treatment. This study identified 14 days after starting rhGH treatment as the optimal time for assessing CNP and NTproCNP levels as biomarkers of rhGH efficacy. Additionally, we identified GH levels as a potential biomarker. Larger, prospective studies are now needed to test the clinical utility of these biomarkers. © 2016 John Wiley & Sons Ltd.

Clinical Evaluation of Insulin like Growth Factor-I and Vascular Endothelial Growth Factor with Alloplastic Bone Graft Material in the Management of Human Two Wall Intra-Osseous Defects

PubMed Central

Dixit, Jaya

2016-01-01

Introduction In recent years, emphasis on the use of growth factors for periodontal healing is gaining great momentum. Several growth factors showed promising results in periodontal regeneration. Aim This study was designed to compare the clinical outcomes of 0.8μg recombinant human Vascular Endothelial Growth Factor (rh-VEGF) and 10μg recombinant human Insulin Like Growth Factor-I (rh-IGF-I) with β-Tricalcium Phosphate (β-TCP) and Polylactide-Polyglycolide Acid (PLGA) membrane in two wall intra-osseous defects. Materials and Methods A total of 29 intra-osseous defects in 27 subjects were randomly divided into 3 test and 1 control group. Test group I (n=8) received rh-VEGF+ rh-IGF-I, Test group II (n=7) rh-VEGF, Test group III (n=7) rh-IGF-I and control group (n=7) with no growth factor, β-TCP and PLGA membrane was used in all the groups. Baseline soft tissue parameters including Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), and Gingival Recession (GR) at selected sites were recorded at baseline and at 6 months. Intrasurgically, intra-osseous component was calculated as a) Cemento-Enamel Junction to Bone Crest (CEJ to BC), b) Bone Crest to Base of the Defect (BC to BD) at baseline and at re-entry. The mean changes at baseline and after 6 months within each group were compared using Wilcoxon Signed Rank Test. The mean changes for each parameter between groups were compared using Mann-Whitney U test. Results After 6 months, maximum mean PPD reduction occurred in test group I followed by test group II, III and control group. Similar trend was observed in CAL gain. Non-significant GR was present in test group I and control group whereas in test group II and III GR was absent. The use of rh-VEGF+ rhIGF-I exhibited 95.8% osseous fill as compared to 54.8% in test group II, 52.7% in test group III and 41.1 % in the control group. Conclusion Within the limitations of this study, it can be concluded that, rh-IGF-I+rh-VEGF treated sites resulted in greater improvement in PPD reduction, CAL gain as well as in osseous fill after 6 months when compared with rh-VEGF, rh-IGF-I and control sites. PMID:27790578

Relationship between Serum Iron Profile and Blood Groups among the Voluntary Blood Donors of Bangladesh.

PubMed

Hoque, M M; Adnan, S D; Karim, S; Al-Mamun, M A; Faruki, M A; Islam, K; Nandy, S

2016-04-01

Blood donation results in a substantial iron loss and subsequent mobilization from body stores. Chronic iron deficiency is a well-recognized complication of regular blood donation. The present study conducted to compare the level of serum ferritin, serum iron, total iron binding capacity (TIBC) and percentage transferrin saturation in different ABO and Rhesus type blood groups among the voluntary blood donors of Bangladesh. The present prospective study included 100 healthy voluntary donors attending at Department of Blood Transfusion, Dhaka Medical College, Dhaka between the periods of July 2013 to Jun 2014. From each donor 10mL venous blood sample was taken and divided into heparinized and non-heparinized tubes for determination of hemoglobin (Hb), hematocrit (Hct), serum iron (SI), total iron binding capacity (TIBC) and serum ferritin by standard laboratory methods. Percentage of transferrin saturation (TS) calculated from serum iron and TIBC. Data were analyzed with SPSS (version 16) software and comparisons between groups were made using student's t-test and one way ANOVA. In the present study mean±SD of age of the respondents was 27.2±6.5 years with a range of 18 to 49 years and 81.0% were male and 19.0% were female. Among the donors 18.0% had blood group A, 35.0% had blood group B, 14.0% had blood group AB and 33.0% had blood group O. Among the donors 91.0% had rhesus positive and 9.0% had rhesus negative. Donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels. Donors with blood group A had highest TIBC level. Donors with blood group B had lowest serum ferritin level. An independent samples 't' test showed statistically significant difference in serum ferritin and percentage transferrin saturation between blood group AB and blood group O and in percentage transferrin saturation between blood group B and blood group O. One way ANOVA showed that there is no significant difference in haemoglobin, serum iron, serum ferritin and percentage transferring saturation in different ABO and Rh blood grouping categories. Blood donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels and donors with blood group A had highest TIBC level. Blood donors with blood group B had lowest serum ferritin level. The understanding of the different blood groups ability to retain iron in their system can give an insight into their ability to handle the disease iron deficiency anaemia.

Lifestyle Modification for Resistant Hypertension: The TRIUMPH Randomized Clinical Trial

PubMed Central

Blumenthal, James A.; Sherwood, Andrew; Smith, Patrick J.; Mabe, Stephanie; Watkins, Lana; Lin, Pao-Hwa; Craighead, Linda W.; Babyak, Michael; Tyson, Crystal; Young, Kenlyn; Ashworth, Megan; Kraus, William; Liao, Lawrence; Hinderliter, Alan

2015-01-01

Background Resistant hypertension (RH) is a growing health burden in this country affecting as many as one in five adults being treated for hypertension. RH is associated with increased risk of adverse cardiovascular disease (CVD) events and all-cause mortality. Strategies to reduce blood pressure in this high risk population are a national priority. Methods TRIUMPH is a single site, prospective, randomized clinical trial (RCT) to evaluate the efficacy of a center-based lifestyle intervention consisting of exercise training, reduced sodium and calorie DASH eating plan, and weight management compared to standardized education and physician advice in treating patients with RH. Patients (N=150) will be randomized in a 2:1 ratio to receive either a 4-month supervised lifestyle intervention delivered in the setting of a cardiac rehabilitation center or to a standardized behavioral counseling session to simulate real-world medical practice. The primary end point is clinic blood pressure; secondary endpoints include ambulatory blood pressure and an array of CVD biomarkers including left ventricular hypertrophy, arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, lipids, sympathetic nervous system activity, and inflammatory markers. Lifestyle habits, blood pressure and CVD risk factors also will be measured at one year follow-up. Conclusions The TRIUMPH randomized clinical trial (ClinicalTrials.gov NCT02342808) is designed to test the efficacy of an intensive, center-based lifestyle intervention compared to a standardized education and physician advice counseling session on blood presssure and CVD biomarkers in patients with RH after 4 months of treatment, and will determine whether lifestyle changes can be maintained for a year. PMID:26542509

The effect of rivastigmine on the LPS-induced suppression of GnRH/LH secretion during the follicular phase of the estrous cycle in ewes.

PubMed

Herman, A P; Krawczyńska, A; Bochenek, J; Haziak, K; Romanowicz, K; Misztal, T; Antushevich, H; Herman, A; Tomaszewska-Zaremba, D

2013-05-01

This study was designed to determine the effect of a potent subcutaneously injected acetylcholinesterase inhibitor, rivastigmine (6mg/animal), on the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release during inflammation induced by an intravenous lipopolysaccharide (LPS) (400ng/kg) injection in ewes during the follicular phase of the estrous cycle. The results are expressed as the mean values from -2 to -0.5h before and +1 to +3h after treatment. Rivastigmine decreased the acetylcholinesterase concentration in the blood plasma from 176.9±9.5 to 99.3±15.1μmol/min/ml. Endotoxin suppressed LH (5.4±0.6ng/ml) and GnRH (4.6±0.4pg/ml) release; however, the rivastigmine injection restored the LH concentration (7.8±0.8ng/ml) to the control value (7.8±0.7ng/ml) and stimulated GnRH release (7.6±0.8pg/ml) compared to the control (5.9±0.4pg/ml). Immune stress decreased expression of the GnRH gene and its receptor (GnRH-R) in the median eminence as well as LHβ and GnRH-R in the pituitary. In the case of the GnRH and LHβ genes, the suppressive effect of inflammation was negated by rivastigmine. LPS stimulated cortisol and prolactin release (71.1±14.7 and 217.1±8.0ng/ml) compared to the control group (9.0±5.4 and 21.3±3.5ng/ml). Rivastigmine also showed a moderating effect on cortisol and prolactin secretion (43.1±13.1 and 169.7±29.5ng/ml). The present study shows that LPS-induced decreases in GnRH and LH can be reduced by the AChE inhibitor. This action of the AChE inhibitor could result from the suppression of pro-inflammatory cytokine release and the attenuation of the stress response. However, a direct stimulatory effect of ACh on GnRH/LH secretion should also be considered. Copyright © 2013 Elsevier B.V. All rights reserved.

The NMDA Receptor Subunit NR2b: Effects on LH Release and GnRH Gene Expression in Young and Middle-aged Female Rats, with Modulation by Estradiol

PubMed Central

Maffucci, Jacqueline A.; Walker, Deena M.; Ikegami, Aiko; Woller, Michael J.; Gore, Andrea C.

2008-01-01

The loss of reproductive capacity during aging involves changes in the neural regulation of the hypothalamic gonadotropin-releasing hormone (GnRH) neurons controlling reproduction. This neuronal circuitry includes glutamate receptors on GnRH neurons. Previously, we reported an increase in the expression of the NR2b subunit protein of the NMDA receptor on GnRH neurons in middle-aged compared to young female rats. Here, we examined the functional implications of the NR2b subunit on the onset of reproductive aging, using an NR2b-specific antagonist ifenprodil. Young (3–5 mos.) and middle-aged (10–13 mos.) female rats were ovariectomized (OVX), 17β-estradiol (E2) or vehicle (cholesterol) treated, and implanted with a jugular catheter. Serial blood sampling was undertaken every 10 minutes for 4 hours, with ifenprodil (10mg/kg) or vehicle injected (i.p.) after one hour of baseline sampling. The pulsatile release of pituitary LH and levels of GnRH mRNA in hypothalamus were quantified as indices of the reproductive axis. Our results showed effects of ifenprodil on both endpoints. In OVX rats given cholesterol, neither age nor ifenprodil had any effects on LH release. In E2-treated rats, aging was associated with significant decreases in pulsatile LH release. Additionally, ifenprodil stimulated parameters of pulsatile LH release in both young and middle-aged animals. Ifenprodil had few effects on GnRH mRNA; the only significant effect of ifenprodil was found in the middle-aged, cholesterol group. Together, these findings support a role for the NR2b subunit of the NMDAR in GnRH/LH regulation. Because most of these effects were exhibited on pituitary LH release in the absence of a concomitant change in GnRH gene expression, it is likely that NMDA receptors containing the NR2b subunit plays a role in GnRH-induced LH release, independent of de novo GnRH gene expression. PMID:18025808

[Mobilization of autologous peripheral blood stem cells by cyclophosphamide and recombinant human granulocyte colony-stimulating factor(rhG-CSF)].

PubMed

Shi, Y; Zhou, S; Han, X

1998-08-01

To observe the effect of cyclophosphamide (CTX) and recombinant human granulocyte colony-stimulating factor(rhG-CSF, Filgrastim) on autologous peripheral blood stem cells (APBSC) mobilization. CTX (3.7 +/- 0.2) g/m2 was intravenously injected the first day. rhG-CSF (4.5 +/- 0.6) micrograms.kg-1.d-1 was injected subcutaneously from the day of white blood cell (WBC) nadir to the day before the end of APBSC harvest. APBSC harvest was started when WBC > 2.5 x 10(9)/L and finished when accumulated mononuclear cells (MNC) of APBSC > 5 x 10(8)/kg. CFU-GM, BFU-E culture and CD34+ cells detection of the APBSC was performed. Twenty cases underwent the APBSC mobilization. The nadir of WBC was (1.1 +/- 0.5) x 10(9)/L at day (9 +/- 1). rhG-CSF was injected from day (10 +/- 1) and continued for (6 +/- 1) days. APBSC harvest began on day (13 +/- 1) and continued for (4 +/- 1) days. Accumulated MNC harvest was (8.4 +/- 1.9) x 10(8)/kg, CFU-GM (18.7 +/- 10.3) x 10(4)/kg, BFU-E (18.5 +/- 8.7) x 10(4)/kg, and CD34+ cells (20.9 +/- 5.7) x 10(6)/kg. No severe toxicity was observed. Hematopoietic reconstitution was very well in 18 patients received the APBSC transplantation. CTX combined with rhG-CSF was a safe and highly effective method for APBSC mobilization.

Detection of recombinant EPO in blood and urine samples with EPO WGA MAIIA, IEF and SAR-PAGE after microdose injections.

PubMed

Dehnes, Yvette; Shalina, Alexandra; Myrvold, Linda

2013-01-01

The misuse of microdoses of performance enhancing drugs like erythropoietin (EPO) constitutes a major challenge in doping analysis. When injected intravenously, the half-life of recombinant human EPO (rhEPO) like epoetin alfa, beta, and zeta is only a few hours and hence, the window for direct detection of rhEPO in urine is small. In order to investigate the detection window for rhEPO directly in blood and urine with a combined affinity chromatography and lateral flow immunoassay (EPO WGA MAIIA), we recruited nine healthy people who each received six intravenously injected microdoses (7.5 IU/kg) of NeoRecormon (epoetin beta) over a period of three weeks. Blood and urine samples were collected in the days following the injections and analyzed with EPO WGA MAIIA as well as the current validated methods for rhEPO; isoelectric focusing (IEF) and sarcosyl polyacrylamide gel electrophoresis (SAR-PAGE). For samples collected 18 h after a microdose, the sensitivity of the EPO WGA MAIIA assay was 100% in plasma and 87.5% in urine samples at the respective 98% specificity threshold levels. In comparison, the sensitivity in plasma and urine was 75% and 100%, respectively, with IEF, and 87.5% in plasma and 100% in urine when analyzed with SAR-PAGE. We conclude that EPO WGA MAIIA is a sensitive assay for the detection of rhEPO, with the potential of being a fast, supplemental screening assay for use in doping analysis.

Detection of rare blood group, Bombay (Oh) phenotype patients and management by acute normovolemic hemodilution.

PubMed

Shrivastava, Manisha; Navaid, Seema; Peethambarakshan, A; Agrawal, Kalpana; Khan, Athar

2015-01-01

Due to lack of correct blood grouping practices, the rare Bombay Oh phenotype may be missed, subjecting patients to the risk of severe hemolytic transfusion reaction. In the absence of blood donor registry, transfusion management of patients needing immediate surgery is a challenge. This study presents detection of rare Bombay Oh phenotype patients and their management by acute peri-operative acute normovolemic hemodilution (ANH) in a hospital from central India. Blood grouping of patients and blood donors with a standard tube method was carried out and samples identified as rare Bombay phenotype were confirmed by saliva inhibition test. Surgical management of cases needing transfusion was done by ANH, as per the British Committee for Standards in Hematology guidelines. The incidence of Bombay phenotype was 0.002% or 1 in 51,924 in the study. Amongst three cases (patients) identified as Bombay phenotype, one was Bombay Oh, Rh negative. Two cases were missed in the first instance and one case actually did not require transfusion. In the absence of a blood donor registry for Bombay phenotype, the cases needing transfusion were successfully managed with ANH in the operation theatre. A simple test like blood grouping should be done with serious intention with incorporation of both forward and reverse grouping, so that no patient receives wrong blood leading to fatal hemolysis due to transfusion. ANH is a cost-effective transfusion option for suitable patients. Appropriate clinical decision making, use of strategies to decrease peri-operative blood losses and cost-effective country based planning could be more widely applied to improve clinical transfusion practice.

Inability of recombinant human thyrotropin to predict the evolution from subclinical hypothyroidism to overt disease. A pilot study.

PubMed

Zafon, C; Rodríguez, B; Montoro, J B; Cabo, D; Mesa, J

2012-01-01

The use of recombinant human TSH (rhTSH) is indicated to evaluate thyroid carcinoma patients. In recent years, some authors have reported that rhTSH could serve as a dynamic test of thyroid reserve. The aim of the present study was to determine whether or not rhTSH can predict the evolution from subclinical hypothyroidism (SH) to overt hypothyroidism. Twenty-one women who met the diagnostic criteria of SH were enrolled. All patients received a single dose of rhTSH (0.1 mg). Basal blood samples for TSH, free T4 (fT4), thyroglobulin (Tg), and anti-thyoperoxidase and anti-Tg antibodies were obtained before and 1 day after rhTSH administration. All patients were followed for 2 yr, and blood samples were obtained every 6 months. Twenty-four hours after rhTSH administration, the TSH level increased to >20 mU/l in 14 patients; the serum peak TSH levels remained <10 mU/l in only 5 patients. On follow-up, 7 women (33%) required L-T4 replacement therapy for overt hypothyroidism or a persistent TSH level >10 mlU/l. None of the parameters analyzed differed significantly between patients who developed overt hypothyroidism from those who had persistent SH. The response of thyroid function tests to a single low dose of rhTSH is not useful in identifying those patients with SH who will develop overt hypothyroidism over a 2-yr period.

Resistant Hypertension: Time to Consider the Best Fifth Anti-Hypertensive Treatment.

PubMed

Pio-Abreu, Andrea; Drager, Luciano F

2018-06-16

Resistant hypertension (RH) is a growing clinical condition worldwide associated with target-organ damage and poor prognosis compared to non-resistant counterparts. The purpose of this review is to perform a critical evaluation of preferable drug choices for managing RH highlighting the evidence that significant proportion of patients remained uncontrolled despite using four anti-hypertensive drugs. Until recently, the fourth drug therapy was main derived from personal opinion or small interventional studies. The recent data derived from two multicentric randomized trials, namely PATHWAY-2 and ReHOT, pointed spironolactone as the preferable fourth drug therapy in patients with confirmed RH as compared to bisoprolol and doxazosin (PATHWAY-2) as well as clonidine (ReHOT). However, significant proportion of patients (especially observed in ReHOT trial that used 24-h ambulatory blood pressure monitoring) did not achieve optimal blood pressure with the fourth drug. This finding underscores the need of new approaches and treatment options in this important research area. The current evidence pointed that significant proportion of RH patients are requiring more than four drugs for controlling BP. This statement is particularly true considering the new criteria proposed by the 2017 Guidelines for diagnosing RH (> 130 × 80 mmHg). New combinations, drugs, or treatments should be tested aiming to reduce the RH burden. Based on the aforementioned multicentric trials, we proposed the first five preferable anti-hypertensive classes in the overall context of RH.

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection

PubMed Central

Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Background: Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. Methods: In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ2-test were used to compare the groups. The p<0.05 was considered to show a statistically significant result. Results: The mean total gonadotropin doses were 3814±891 IU in group 1 and 3539±877 IU in group 2 (p=0.02). The number of metaphase-II oocytes (3.6±2.4 vs. 2.8±1.9, p=0.005) and implantation rates (27.8% vs. 18.8%, p=0.04) in group 1 and group 2, respectively were significantly different. The fertilization rate in group 1 and group 2 was 73% vs. 68%, respectively (p=0.5) and clinical pregnancy rate was 19.8% vs. 14.4%, respectively (p=0.13). Conclusion: The GnRH agonist microdose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders. PMID:27478770

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection.

PubMed

Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ (2)-test were used to compare the groups. The p<0.05 was considered to show a statistically significant result. The mean total gonadotropin doses were 3814±891 IU in group 1 and 3539±877 IU in group 2 (p=0.02). The number of metaphase-II oocytes (3.6±2.4 vs. 2.8±1.9, p=0.005) and implantation rates (27.8% vs. 18.8%, p=0.04) in group 1 and group 2, respectively were significantly different. The fertilization rate in group 1 and group 2 was 73% vs. 68%, respectively (p=0.5) and clinical pregnancy rate was 19.8% vs. 14.4%, respectively (p=0.13). The GnRH agonist microdose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders.

High diagnostic accuracy of subcutaneous Triptorelin test compared with GnRH test for diagnosing central precocious puberty in girls.

PubMed

Freire, Analía Verónica; Escobar, María Eugenia; Gryngarten, Mirta Graciela; Arcari, Andrea Josefina; Ballerini, María Gabriela; Bergadá, Ignacio; Ropelato, María Gabriela

2013-03-01

The GnRH test is the gold standard to confirm the diagnosis of central precocious puberty (CPP); however, this compound is not always readily available. Diagnostic accuracy of subcutaneous GnRH analogues tests compared to classical GnRH test has not been reported. To evaluate the diagnostic accuracy of Triptorelin test (index test) compared to the GnRH test (reference test) in girls with suspicion of CPP. A prospective, case-control, randomized clinical trial was performed. CPP or precocious thelarche (PT) was diagnosed according to maximal LH response to GnRH test and clinical characteristics during follow-up. Forty-six girls with premature breast development randomly underwent two tests: (i) intravenous GnRH 100 μg, (ii) subcutaneous Triptorelin acetate (0.1 mg/m(2), to a maximum of 0.1 mg) with blood sampling at 0, 3 and 24 h for LH, FSH and estradiol ascertainment. Gonadotrophins and estradiol responses to Triptorelin test were measured by ultrasensitive assays. Clinical features were similar between CPP (n = 33) and PT (n = 13) groups. Using receiver operating characteristic curves, maximal LH response (LH-3 h) under Triptorelin test ≥ 7 IU/l by immunofluorometric assay (IFMA) or ≥ 8 IU/l by electrochemiluminescence immunoassay (ECLIA) confirmed the diagnosis of CPP with specificity of 1.00 (95% CI: 0.75-1.00) and sensitivity 0.76 (95% CI: 0.58-0.89). Considering either LH-3 h or maximal estradiol response at 24 h (cut-off value, 295 pm), maintaining the specificity at 1.00, the test sensitivity increased to 0.94 (95% CI: 0.80-0.99) and the diagnostic efficiency to 96%. The Triptorelin test had high accuracy for the differential diagnosis of CPP vs PT in girls providing a valid alternative to the classical GnRH test. This test also allowed a comprehensive evaluation of the pituitary-ovarian axis. © 2012 Blackwell Publishing Ltd.

Biodistribution and Pharmacodynamics of Recombinant Human Alpha-L-Iduronidase (rhIDU) in Mucopolysaccharidosis Type I-Affected Cats Following Multiple Intrathecal Administrations

PubMed Central

Vite, Charles H.; Wang, Ping; Patel, Reema T.; Walton, Raquel M.; Walkley, Steven U.; Sellers, Rani S.; Ellinwood, N. Matthew; Cheng, Alphonsus S.; White, Joleen T.; O’Neill, Charles A.; Haskins, Mark

2011-01-01

The storage disorder mucopolysaccharidosis type I (MPS I) is caused by a deficiency in lysosomal α-L-iduronidase activity. The inability to degrade glycosaminoglycans (GAG) results in lysosomal accumulation and widespread tissue lesions. Many symptoms of MPS I are amenable to treatment with recombinant human α-L-iduronidase (rhIDU), however, peripherally administered rhIDU does not cross the blood-brain barrier and has no beneficial effects in the central nervous system (CNS). A feline model of MPS I was used to evaluate the CNS effects of rhIDU following repeated intrathecal (IT) administration. Twelve animals were randomized into four groups based on the time of euthanasia and tissue evaluation following three repeat IT administrations of 0.1 mg/kg rhIDU or placebo on Study Days 1, 4 or 5, and 9. Two days after the final IT injection, the mean tissue α-L-iduronidase (IDU) activity in the brains of the two treated animals were approximately 3-times higher (50.1 and 54.9 U/mg protein) than the activity found in normal cat brains (mean of 18.3 U/mg), and remained higher than untreated MPS1 brain at 1 month (2.4 and 4.1 U/mg protein) before returning to near-baseline levels after 2 months. This activity corresponded with decreased brain GAG concentrations after 2 days (1.4 and 2.0 mcg/mg) and 1 month (0.9 and 1.1 mcg/mg) which approached levels observed in normal animals (0.7 mcg/mg). Attenuation of GAG, gangliosides GM2 and GM3, and cholesterol reaccumulation was identified at both two days and one month following final IT injection. No adverse effects or rhIDU antibody response attributable to IT rhIDU administration were observed. IT rhIDU may be an effective means for providing enzyme replacement therapy for the central manifestations of MPS I. PMID:21482164

Evaluation of the return rate of volunteer blood donors

PubMed Central

Lourençon, Adriana de Fátima; Almeida, Rodrigo Guimarães dos Santos; Ferreira, Oranice; Martinez, Edson Zangiacomi

2011-01-01

Background To convert first-time blood donors into regular volunteer donors is a challenge to transfusion services. Objectives This study aims to estimate the return rate of first time donors of the Ribeirão Preto Blood Center and of other blood centers in its coverage region. Methods The histories of 115,553 volunteer donors between 1996 and 2005 were analyzed. Statistical analysis was based on a parametric long-term survival model that allows an estimation of the proportion of donors who never return for further donations. Results Only 40% of individuals return within one year after the first donation and 53% return within two years. It is estimated that 30% never return to donate. Higher return rates were observed among Black donors. No significant difference was found in non-return rates regarding gender, blood type, Rh blood group and blood collection unit. Conclusions The low percentage of first-time donors who return for further blood donation reinforces the need for marketing actions and strategies aimed at increasing the return rates. PMID:23049294

Malaria invasion ligand RH5 and its prime candidacy in blood-stage malaria vaccine design

PubMed Central

Ord, Rosalynn L; Rodriguez, Marilis; Lobo, Cheryl A

2015-01-01

With drug resistance to available therapeutics continuing to develop against Plasmodium falciparum malaria, the development of an effective vaccine candidate remains a major research goal. Successful interruption of invasion of parasites into erythrocytes during the blood stage of infection will prevent the severe clinical symptoms and complications associated with malaria. Previously studied blood stage antigens have highlighted the hurdles that are inherent to this life-cycle stage, namely that highly immunogenic antigens are also globally diverse, resulting in protection only against the vaccine strain, or that naturally acquired immunity to blood stage antigens do not always correlate with actual protection. The blood stage antigen reticulocyte binding homolog RH5 is essential for parasite viability, has globally limited diversity, and is associated with protection from disease. Here we summarize available information on this invasion ligand and recent findings that highlight its candidacy for inclusion in a blood-stage malaria vaccine. PMID:25844685

Advances in Blood Typing.

PubMed

Quraishy, N; Sapatnekar, S

The clinical importance of blood group antigens relates to their ability to evoke immune antibodies that are capable of causing hemolysis. The most important antigens for safe transfusion are ABO and D (Rh), and typing for these antigens is routinely performed for patients awaiting transfusion, prenatal patients, and blood donors. Typing for other blood group antigens, typically of the Kell, Duffy, Kidd, and MNS blood groups, is sometimes necessary, for patients who have, or are likely to develop antibodies to these antigens. The most commonly used typing method is serological typing, based on hemagglutination reactions against specific antisera. This method is generally reliable and practical for routine use, but it has certain drawbacks. In recent years, molecular typing has emerged as an alternative or supplemental typing method. It is based on detecting the polymorphisms and mutations that control the expression of blood group antigens, and using this information to predict the probable antigen type. Molecular typing methods are useful when traditional serological typing methods cannot be used, as when a patient has been transfused and the sample is contaminated with red blood cells from the transfused blood component. Moreover, molecular typing methods can precisely identify clinically significant variant antigens that cannot be distinguished by serological typing; this capability has been exploited for the resolution of typing discrepancies and shows promise for the improved transfusion management of patients with sickle cell anemia. Despite its advantages, molecular typing has certain limitations, and it should be used in conjunction with serological methods. © 2016 Elsevier Inc. All rights reserved.

The effects of progesterone priming on reproductive performance of GnRH-PGF2alpha-treated anestrous goats.

PubMed

Husein, Mustafa Q; Ababneh, Mohammed M; Haddad, Serhan G

2005-01-01

The objective of this experiment was to determine the effect of a 5-day progesterone priming prior to a GnRH-PGF2alpha treatment on reproductive performance of anestrous goats. Thirty-six Mountain Black goats were randomly assigned in a 2 x 2 factorial arrangement and were administered intravaginally on day -12, either with 300 mg progesterone inserts (CGPE and CGP) or with 0 mg progesterone (GPE and GP) for 5 days. On day -6, the goats were injected with 100 microg GnRH, followed 6 days later by 15 mg PGF2alpha (day 0), the time at which the goats in the CGPE and GPE groups were administered 300 IU eCG injections and those in CGP and GP groups were administered the control solution. The goats were exposed to four fertile bucks at 0 h and were checked for breeding marks at 6-h intervals for 72 h. Blood samples were collected from all goats for progesterone analysis. Progesterone concentrations increased only in CGPE and CGP during the period of device insertion but remained low in GPE and GP groups (P < 0.001). Progesterone levels at the time of GnRH injection on day -6 were basal (0.2 +/- 0.04 ng.mL-1) among the groups and began to increase starting on day -2. Day 0 progesterone concentrations differed (P < 0.05) among groups and were significantly influenced by CIDR-G (P < 0.001). A similar proportion of goats expressed estrus and intervals to detected estrus were shorter (P < 0.05) in the CGPE and GPE groups than in GP with no difference between the CGPE, CGP and GPE or between CGP and GP groups. The number of goats ovulating based upon elevated progesterone levels on day 0 was significantly greater (P = 0.002) in CGPE (9/9) and CGP (9/9) than GPE (6/9) and GP (5/9) groups and was significantly influenced by CIDR-G (P = 0.03). All pregnant goats had elevated progesterone concentration on day 0 and none of the goats with basal progesterone levels became pregnant. Pregnancy and kidding rates, twinning percentage and the number of kids born per goat exposed were greater (P < 0.05) among goats treated with progesterone and eCG. In conclusion, progesterone priming and eCG are essential for producing higher rates of pregnancy and kidding in GnRH-PGF2alpha-treated anestrous goats.

Role of enzyme-treated cells in RBC antibody screening using the gel test: a study of anti-RH1, -RH2, and -RH3 antibodies.

PubMed

Conne, Jocelyne; Schneider, Philippe; Tissot, Jean-Daniel

2007-01-01

The role of enzyme-treated cells (ETCs) in red blood cell (RBC) antibody screening has been the subject of controversy, and its place in the clinical routine remains to be determined. In this work, plasma samples containing anti-RH1 (anti-D; N = 10), anti-RH2 (anti-C; N = 10), or anti-RH3 (anti-E; N = 10) antibodies were studied. The samples were diluted in nonbuffered or buffered normal saline, as well as in a pool of AB plasma samples. Titers and scores were determined by means of the gel test, using the indirect antiglobulin test (IAT) as well as ETCs, with R(0)r, r'r, or r''r test cells. Our results showed that compared to the IAT, ETCs allowed a clearer detection of anti-RH2 and anti-RH3, but not of anti-RH1 antibodies. Based on our study, it is not clear whether the ETC phase of the gel test should be maintained for RBC antibody screening. 2007 Wiley-Liss, Inc.

Sequential promotion of normal and leukemic hemopoiesis by recombinant human granulocyte colony-stimulating factor during the course of myelodysplastic syndrome.

PubMed

Ueda, T; Kawai, Y; Sugiyama, T; Takeuchi, N; Yoshida, A; Iwasaki, H; Wano, Y; Tsutani, H; Kamada, N; Nakamura, T

1993-12-01

A 48-year-old man developed refractory anemia with excess of blasts in transformation. Complete response was achieved by low-dose ara-C therapy, but he relapsed 15 months later, with pancytopenia and 13.0% myeloblasts in normocellular marrow. He was treated unsuccessfully with prednisolone, metenolone, and 1-alpha-hydroxyvitamin D3 for 8 weeks. He then developed life-threatening pneumonia and was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF Filgrastim; 125 micrograms/day s.c.). The pneumonia resolved and, interestingly, he achieved a partial response, with normal blood cell counts and only a few dysmyelopoietic cells in the marrow. However, thrombocytopenia progressed when rhG-CSF administration was tapered. When the dose was increased again, leukemic blasts were found to proliferate. When rhG-CSF was discontinued, blasts rapidly decreased in the peripheral blood. Chromosomal analysis revealed a complex abnormality during the first relapse, a normal 46,XY karyotype during the partial response, and recurrence of the same complex abnormality during leukemic transformation. The stimulation index of marrow mononuclear cells cultured with rhG-CSF increased with disease progression. These findings suggest that rhG-CSF initially stimulated the selective proliferation of normal hemopoietic cells, but the evolution or selection of a leukemic clone responsive to rhG-CSF appears to have occurred subsequently.

Reassessment of ABO blood group, sex, and age on laboratory parameters used to diagnose von Willebrand disorder: potential influence on the diagnosis vs the potential association with risk of thrombosis.

PubMed

Favaloro, Emmanuel J; Soltani, Soma; McDonald, Jane; Grezchnik, Ella; Easton, Leanne; Favaloro, James W C

2005-12-01

We reassessed the influence of ABO blood group, sex, and age on plasma levels of von Willebrand factor (vWF) antigen, vWF:ristocetin cofactor, vWF:collagen binding assay, and factor VIII coagulant (FVIII:C). Data show that levels of vWF and FVIII:C increase with increasing age (P < .001 for all parameters) and that the ABO blood group influences plasma levels such that O group levels are significantly less than non-O group levels. There was no significant association with sex and Rh status. The selection of normal ranges based on ABO blood groups may influence the clinical diagnosis of von Willebrand disease (vWD) but might not be clinically relevant or help identify people at increased risk of bleeding. Differences in ABO-related ranges were more extensive at the high end of the ranges. This is of particular interest because high levels of vWF and FVIII are associated with thrombosis risk, and an ABO relationship also has been described. O group individuals may or may not be at greater risk for bleeding (they have lower levels of vWF and FVIII:C) and are more likely to be diagnosed with vWD. It also is possible that O group status may be protective for thrombosis.

Rhamnolipids as platform molecules for production of potential anti-zoospore agrochemicals.

PubMed

Miao, Shida; Dashtbozorg, Soroosh Soltani; Callow, Nicholas V; Ju, Lu-Kwang

2015-04-08

Rhamnolipid biosurfactants have potential applications in the control of zoosporic plant pathogens. However, rhamnolipids have not been closely investigated for the anti-zoospore mechanism or for developing new anti-zoospore chemicals. In this study, RhL-1 and RhL-3 groups of rhamnolipids were used to generate the corresponding RhL-2 and RhL-4 groups and the free diacids. Conversion of RhL-3 to RhL-1 was also accomplished in vitro with cellobiase as the catalyst. The anti-zoospore effects of RhL-1-RhL-4 and the diacids were investigated with zoospores of Phytophthora sojae. For RhL-1-RhL-4, approximately 20, 30, 40, and 40 mg/L, respectively, were found to be the lowest concentrations required to stop movement of all zoospores, which indicates that the anti-zoospore effect remains strong even after RhL-1 and RhL-3 are hydrolyzed into RhL-2 and RhL-4. The free diacids required a significantly higher critical concentration of about 125 mg/L. Rhamnose can be obtained as a co-product.

Possible Correlation of Transfusion Transmitted Diseases with Rh type and ABO Blood Group System

PubMed Central

Tyagi, Surabhi; Tyagi, Alok

2013-01-01

Background: Screening of blood is mandatory for transfusion transmitted diseases and is routinely done in the blood banks. As blood is the major source transmission of hepatitis B, hepatitis C, human immunodeficiency virus & many other diseases the hazards can be minimised by effective donor selection and screening. Aim: To find out the correlation between the transfusion transmitted diseases and blood groups and the seroprevalence of HIV, HBV, HCV & syphilis among the apparently healthy human blood donors. Study, Setting & Design: This retrospective study was conducted at the blood bank of a tertiary health care teaching centre for a period of four years. Material and Methods: All voluntary and replacement donors reporting to the blood bank were screened for HIV-1 & 2, HBsAg, HCV and Syphilis. Anti–HIV -1 & 2, HBsAg & anti - HCV was tested using the appropriate Enzyme–linked immunosorbent assay (ELISA) technique using micro–elisa kit supplied by J.Mitra & Co.Ltd. The seropositive samples were again tested on ELISA kits of RFCL &/or BIORAD for further confirmation & ruling out any false positive or false negative results. The rapid plasma reagain (RPR) test was used for estimation of syphilis infection. Statistical Analysis: The data entry was carried out using Microsoft office excel worksheet and was analysed by percentage and comparison. Results: Total of 6000 donors were screened which included voluntary and replacement donors. Seroprevalence of HIV (0.1833 %), HCV (1.28%), HBsAg (1.5833 %) and syphilis (0.4333 %) was detected. In the study done it was also noted - that the NEGATIVE blood groups were more prone to TTIs. Blood group A negative was more prone to TTIs with HIV, HBsAg and VDRL while blood group B negative was more affected by HCV. Conclusion: Seroprevalence of these infections shows that routine screening is a must for blood and blood product safe transfusion. Do negative blood groups predispose to TTIs? A finding which makes us think…. PMID:24179900

Possible Correlation of Transfusion Transmitted Diseases with Rh type and ABO Blood Group System.

PubMed

Tyagi, Surabhi; Tyagi, Alok

2013-09-01

Screening of blood is mandatory for transfusion transmitted diseases and is routinely done in the blood banks. As blood is the major source transmission of hepatitis B, hepatitis C, human immunodeficiency virus & many other diseases the hazards can be minimised by effective donor selection and screening. To find out the correlation between the transfusion transmitted diseases and blood groups and the seroprevalence of HIV, HBV, HCV & syphilis among the apparently healthy human blood donors. Study, Setting & Design: This retrospective study was conducted at the blood bank of a tertiary health care teaching centre for a period of four years. All voluntary and replacement donors reporting to the blood bank were screened for HIV-1 & 2, HBsAg, HCV and Syphilis. Anti-HIV -1 & 2, HBsAg & anti - HCV was tested using the appropriate Enzyme-linked immunosorbent assay (ELISA) technique using micro-elisa kit supplied by J.Mitra & Co.Ltd. The seropositive samples were again tested on ELISA kits of RFCL &/or BIORAD for further confirmation & ruling out any false positive or false negative results. The rapid plasma reagain (RPR) test was used for estimation of syphilis infection. The data entry was carried out using Microsoft office excel worksheet and was analysed by percentage and comparison. Total of 6000 donors were screened which included voluntary and replacement donors. Seroprevalence of HIV (0.1833 %), HCV (1.28%), HBsAg (1.5833 %) and syphilis (0.4333 %) was detected. In the study done it was also noted - that the NEGATIVE blood groups were more prone to TTIs. Blood group A negative was more prone to TTIs with HIV, HBsAg and VDRL while blood group B negative was more affected by HCV. Seroprevalence of these infections shows that routine screening is a must for blood and blood product safe transfusion. Do negative blood groups predispose to TTIs? A finding which makes us think….

Water vapour and heat combine to elicit biting and biting persistence in tsetse

PubMed Central

2013-01-01

Background Tsetse flies are obligatory blood feeders, accessing capillaries by piercing the skin of their hosts with the haustellum to suck blood. However, this behaviour presents a considerable risk as landing flies are exposed to predators as well as the host’s own defense reactions such as tail flicking. Achieving a successful blood meal within the shortest time span is therefore at a premium in tsetse, so feeding until replete normally lasts less than a minute. Biting in blood sucking insects is a multi-sensory response involving a range of physical and chemical stimuli. Here we investigated the role of heat and humidity emitted from host skin on the biting responses of Glossina pallidipes, which to our knowledge has not been fully studied in tsetse before. Methods The onset and duration of the biting response of G. pallidipes was recorded by filming movements of its haustellum in response to rapid increases in temperature and/or relative humidity (RH) following exposure of the fly to two airflows. The electrophysiological responses of hygroreceptor cells in wall-pore sensilla on the palps of G. pallidipes to drops in RH were recorded using tungsten electrodes and the ultra-structure of these sensory cells was studied by scanning and transmission electron microscopy. Results Both latency and proportion of tsetse biting are closely correlated to RH when accompanied by an increase of 13.1°C above ambient temperature but not for an increase of just 0.2°C. Biting persistence, as measured by the number of bites and the time spent biting, also increases with increasing RH accompanied by a 13.1°C increase in air temperature. Neurones in wall-pore sensilla on the palps respond to shifts in RH. Conclusions Our results show that temperature acts synergistically with humidity to increase the rapidity and frequency of the biting response in tsetse above the levels induced by increasing temperature or humidity separately. Palp sensilla housing hygroreceptor cells, described here for the first time in tsetse, are involved in the perception of differences in RH. PMID:23958224

Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage Following Destabilization of the Medial Meniscus in the Yucatan Minipig

PubMed Central

Waller, Kimberly A.; Chin, Kaitlyn E.; Jay, Gregory D.; Zhang, Ling X.; Teeple, Erin; McAllister, Scott; Badger, Gary J.; Schmidt, Tannin A.; Fleming, Braden C.

2016-01-01

Background Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been previously shown to be down-regulated following traumatic joint injury such as a meniscal tear. There is preliminary evidence suggesting that intra-articular injection of PRG4 post-injury will reduce cartilage damage in rat models of surgically-induced post-traumatic osteoarthritis. Objective To determine the efficacy of intra-articular injection of full length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscus destabilization (DMM) in a pre-clinical large animal model. Study Design Controlled laboratory study Methods Unilateral DMM was performed in 29 Yucutan minipigs. One week post-DMM, animals received 3 weekly intra-articular injections (3cc/injection): 1) rhPRG4 [1.3mg/ml; n=10], 2) rhPRG4+hyaluronan [1.3mg/ml rhPRG4 and 3mg/ml hyaluronan (~950 kDA); n=10], and 3) phosphate buffered saline [PBS; n=9]. Hind limbs were harvested 26 weeks post-surgery. Cartilage integrity was evaluated using macroscopic (India Ink) and microscopic (Safranin O-fast green and hematoxylin & eosin) scoring systems. Secondary outcomes evaluated using ELISA included PRG4 levels in synovial fluid, CTX-II concentrations in urine and serum, and IL-1β levels in synovial fluid and serum. Results The rhPRG4 group had significantly less macroscopic cartilage damage in the medial tibial plateau compared to the PBS group (p=.002). No difference was found between the rhPRG4+hyaluronan and PBS groups (p=.23). However, no differences in microscopic damage scores were observed between the three groups (p=.70). PRG4 production was elevated in the rhPRG4 group synovial fluid compared to the PBS group (p=.033). The rhPRG4 group presented significantly lower urinary CTX-II levels, but not serum levels, when compared to the PBS (p=.013) and rhPRG4+hyaluronan (p=.011) groups. In serum and synovial fluid, both rhPRG4 (p=.006; p=.017) and rhPRG4+hyaluronan groups (p=.009; p=.03) presented decreased IL-1β levels. Conclusion All groups exhibited significant cartilage degeneration following DMM surgery. However, animals treated with rhPRG4 had the least amount of cartilage damage and less inflammation, providing evidence that intra-articular injections of rhPRG4 may slow the progression of post-traumatic osteoarthritis. Clinical Relevance Patients with meniscal trauma are at high risk for post-traumatic osteoarthritis. This study demonstrates that an intra-articular injection regimen of rhPRG4 may attenuate cartilage damage following meniscal injury. PMID:28129516

Intra-articular Enzyme Replacement Therapy with rhIDUA is Safe, Well-Tolerated, and Reduces Articular GAG Storage in the Canine Model of Mucopolysaccharidosis Type I

PubMed Central

Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William; Lawrence, Roger; Ellinwood, N. Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

2014-01-01

Background Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Methods Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for six months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and one month following the final injection. Results All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints was 8.62±5.86 μg/mg dry weight and 21.6±10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113±39.5 ng/g wet weight) compared to saline-treated joints (142±56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was abolished in rhIDUA-treated joints only. Conclusions Intra-articular rhIDUA is well-tolerated and safe in the canine MPS I animal model. Qualitative and quantitative assessments indicate that IA-rhIDUA successfully reduces tissue and cellular GAG storage in synovium and articular cartilage, including cartilage deep to the articular surface, and eliminates inflammatory macrophages from synovial tissue. PMID:24951454

Allogeneic blood stem cell transplantation: considerations for donors.

PubMed

Anderlini, P; Körbling, M; Dale, D; Gratwohl, A; Schmitz, N; Stroncek, D; Howe, C; Leitman, S; Horowitz, M; Gluckman, E; Rowley, S; Przepiorka, D; Champlin, R

1997-08-01

Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is now being increasingly performed, but safety considerations for hematologically normal PBSC donors have not been fully addressed. Progenitors are generally mobilized for collection from normal donors using recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety profile of rhG-CSF seems acceptable, experience remains limited and its optimal dose and schedule have not been defined. Minimal data exist regarding long-term safety of rhG-CSF, primarily derived from experience in patients with chronic neutropenia or cancer. An "ad hoc" workshop was recently convened among a group of investigators actively involved in the field of allogeneic stem cell transplantation to discuss the safety issues pertaining to normal PBSC donors. There was agreement on the following points: (1) On the basis of available data, it appears that rhG-CSF treatment and PBSC collection have an acceptable short-term safety profile in normal donors. However, the need for continued safety monitoring was recognized. (2) rhG-CSF doses up to 10 microg/kg/d show a consistent dose-response relationship with the mobilization (and collection) of CD34+ progenitor cells, and this dose is acceptable for routine clinical use. Whether higher doses are superior (or cost effective) remains to be determined, and they may produce more severe side effects. The potential risks of marked leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L) have been a concern, and rhG-CSF dose reduction is performed by many centers to maintain leukocyte counts below this level. (3) Transient post donation cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are at least partly related to the leukapheresis procedure. These are generally asymptomatic and self-limited; follow-up blood counts are not necessarily required. Reinfusion of autologous platelet-rich plasma should be considered for donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x 10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors of apheresis platelets, with the exception that pediatric donors may also be considered. Any deviation from these criteria should have supporting documentation. There is insufficient information at this time to clearly establish definite contraindications for PBSC collection in a hematologically normal donor. Potential contraindications include the presence of inflammatory, autoimmune, or rheumatologic disorders, as well as atherosclerotic or cerebrovascular disease. (5) The creation of an International PBSC Donor Registry is desirable to facilitate monitoring the long-term effects of the procedure. Individual institutions or donor centers are encouraged to establish their own PBSC donor follow-up system, preferably with a standardized approach to data collection.

Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

PubMed

Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

2017-11-01

Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered ( P <0.0001). Metabolic concentrations were quantified and ranged from ng/mL malate to μg/mL citrate. Citrate and oxaloacetate increased in RH versus pseudoresistant. Together with α-ketoglutarate and malate, they were able to discriminate between responders and nonresponders, being the 4 metabolites increased in nonresponders. Combined as a prediction panel, they showed receiver operating characteristiccurve with area under the curve of 0.96. We show that citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

Short-term systemic insulin-like growth factor-1 is unable to prevent cyclosporin A-induced osteopenia in the rat.

PubMed

Mann, G N; Sass, D A; Chen, H K; Buchinsky, F J; Bryer, H P; Ma, Y F; Jee, W S; Rucinski, B; Epstein, S

1996-07-01

Immunosuppression with cyclosporin A (CsA) is effective in a number of immune-mediated diseases and in preventing rejection following organ transplantation. We have repeatedly demonstrated that CsA in the rat model produces accelerated bone remodelling with net bone loss, best characterized in trabecular bone. IGF-I holds promise as a treatment for various osteopenic conditions. Although currently a subject of much controversy, various studies have suggested that in vivo it is anabolic to cortical as well as trabecular bone. The purpose of this study was, in part, to further characterize the effects of CsA and IGF-I on trabecular and cortical bone, and to see whether systemic IGF-I is able to modulate CsA's deleterious skeletal effects. Sixty 10 week-old, male, Sprague-Dawley rats were randomized to receive the following daily for 3 weeks: (1) CsA vehicle (veh) per os (po) + recombinant human (rh) IGF-1 veh subcutaneously (sc); (2) CsA 15 mg/kg po + rhIGF-I-veh; (3) CsA-veh + rhIGF-I 200 microg/kg sc; (4) CsA-veh + rhIGF-I 600 microg/kg sc; (5) CsA 15 mg/kg + rhIGF-I 200 microg/kg, and (6) CsA 15 mg/kg + rhIGF-I 600 microg/kg. Rats were weighed and venous blood was sampled serially for determination of glucose, ionized calcium (Ca2+), PTH, vitamin D, and osteocalcin. Following sacrifice on day 20, histomorphometry was performed on double calcein-labeled tibial metaphysis and diaphysis. All rats receiving CsA had elevated levels of blood glucose and osteocalcin by day 9 and vitamin D at day 20. PTH was similar in all groups, and Ca2+ was only raised in the CsA and CsA + IGF-I 200 microg/kg groups. Rats receiving IGF-I 200 microg/kg and IGF-I 600 microg/kg gained more weight than either vehicle- or CsA-treated animals, attesting to IGF-1's anabolic properties. CsA caused severe trabecular bone loss, not prevented by IGF-I; it even further increased the eroded surface. CsA and IGF-I had little effect on cortical bone volume or marrow area. IGF-I increased endocortical matrix synthesis, as evidenced by the increases in the percent endocortical osteoid perimeter, an effect negated by the addition of CsA. This experiment demonstrates that trabecular bone is more susceptible than cortical bone to the deleterious effects of CsA and indicates little role for IGF-1 in the pathophysiology or treatment of CsA-induced bone disease at the given doses and duration of treatment.

The wnt/β-catenin signaling pathway participates in rhein ameliorating kidney injury in DN mice.

PubMed

Duan, Suyan; Wu, Yingyi; Zhao, Chuanyan; Chen, Mingyu; Yuan, Yanggang; Xing, Changying; Zhang, Bo

2016-01-01

The present study aimed to investigate the relationship between wnt/β-catenin signaling pathway and kidney impairment in diabetic nephropathy (DN) mice as well as the renoprotective effect of rhein (RH). Mice were randomly divided into four groups (n = 6): db/db mice treated with RH (DN + RH), db/db mice (DN), db/m mice treated with RH (NC + RH) and db/m mice (NC). RH-treated groups were administered orally at a daily dose 120 mg/kg. Mice were sacrificed after 12 weeks of treatments. In our study, increased albuminuria, together with weight gain and hyperglycemia was observed in the beginning of the study and continued to increase throughout the length of the study (12 weeks). Histopathologic changes were observed in the DN group. Expectedly, mice receiving the treatment with RH were protected from this injury. Meanwhile, the expression of nephrin, a podocyte-specific marker, was significantly reduced while wnt1, p-GSK-3β/tGSK-3β, p-β-catenin/tβ-catenin were higher in the DN group mice when analyzed by immunofluorescence and Western blotting. RH reversed these above changes. wnt/β-catenin signaling pathway participates in RH ameliorating kidney injury in DN mice. The manipulation of RH might act as a promising therapeutic intervention for DN.

Ammonia concentration and relative humidity in poultry houses affect the immune response of broilers.

PubMed

Wei, F X; Hu, X F; Xu, B; Zhang, M H; Li, S Y; Sun, Q Y; Lin, P

2015-04-10

To investigate the effect of ammonia (NH3) and humidity on the immune response of broilers, broilers were exposed to 30 or 70 mg/kg atmospheric NH3 for 21 days. Additionally, birds were exposed to 35, 60, and 85% relative humidity (RH). The relative weights of lymphoid organs, serum total protein, serum globulin, serum albumin, serum lysozyme, proliferation index of peripheral blood lymphocytes, and splenic cytokine gene expression were determined. Exposure to 70 mg/kg NH3 decreased the relative weight of the spleen during the experimental period, serum lysozyme concentration in the first and second weeks, and serum globulin concentration in the third week. The proliferation of peripheral blood lymphocytes was reduced. High levels of NH3 caused increase in IL-1β gene expression in the experimental period and IL-4 gene expression in the first week. Birds exposed to 85% RH had lower thymus and bursa of Fabricius weights in the third week and serum lysozyme concentration in the first week; IL-1β and IL-4 expressions were higher in the second and third weeks and first and second weeks, respectively, than in birds exposed to 60% RH. IL-4 expression was lower during the first week, and IL-1β expression was higher during the second week with 35% RH than with 60% RH. In conclusion, high NH3 level in the poultry house suppressed the immune response of broiler chickens. Neither high nor low RH benefited the immune response of broilers. Furthermore, there was an interactive effect between NH3 and RH on the immune response of broilers.

Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

PubMed

Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

2014-08-01

Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was abolished in rhIDUA-treated joints only. Intra-articular rhIDUA is well-tolerated and safe in the canine MPS I animal model. Qualitative and quantitative assessments indicate that IA-rhIDUA successfully reduces tissue and cellular GAG storage in synovium and articular cartilage, including cartilage deep to the articular surface, and eliminates inflammatory macrophages from synovial tissue. The MPS I canine IA-rhIDUA results suggest that clinical studies should be performed to determine if IA-rhIDUA is a viable approach to ameliorating refractory orthopedic disease in human MPS I. Copyright © 2014 Elsevier Inc. All rights reserved.

Donor lymphocyte apheresis for adoptive immunotherapy compared with blood stem cell apheresis.

PubMed

Körbling, M; Giralt, S; Khouri, I; Mirza, N; Donato, M; Anderlini, P; Fischer, H; Andreeff, M; McMannis, J; Champlin, R

2001-01-01

Donor lymphocyte transfusion has gained considerable interest as adoptive cellular immunotherapy for prevention or treatment of relapse after allogeneic stem cell transplantation. This study was designed to compare the yield of CD3(+), CD3(+)4(+), CD3(+)8(+), CD19(+), CD3(-)56(+)16(+), and CD34(+) cells contained in apheresis products from 61 consecutive non-cytokine treated, human leukocyte antigen (HLA)-matched donors for lymphocyte collection with the corresponding apheresis-derived cell yield from 112 consecutive, HLA-matched donors for blood stem cell collection who received recombinant human granulocyte colony stimulating factor (rhG-CSF, filgrastim) 6 microg/kg every 12 hours until cell collection was completed. Apheresis was started on day 4 or 5 of rhG-CSF treatment. The yield of lymphoid subsets was significantly different in the two sample groups, rhG-CSF treated product yields exceeding untreated product yields by a median of 2.1-fold (range: 1.3-2.6). However, the CD34(+) cell yield in rhG-CSF-treated apheresis products exceeded untreated products by 26-fold. A single untreated apheresis procedure was usually sufficient to collect a target dose of 1 x 10(8)/kg CD3(+) cells. Untreated apheresis products contained a median of 0.2 x 10(6)/kg CD34(+) cells. A potential engraftment dose of > or =0.5 x 10(6) CD34(+) cells per kg of recipient body weight was contained in 16% of 57 untreated apheresis products. One single apheresis performed in a normal, untreated donor provides a sufficient amount of CD3(+) cells for adoptive immunotherapy. Compared with that of an rhG-CSF stimulated apheresis product, the CD34(+) cell count is usually, but not always, below the engraftment dose range. RhG-CSF treatment has little effect on the yield of lymphoid subsets collected by apheresis but is highly selective of the release of CD34(+) cells. This report provides baseline data for studies that will show whether other cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF) and/or Flt-3 Ligand can immunomodulate allotransfusates in vivo to improve the graft-vs.-leukemia (GVL) effect after allogeneic stem cell transplantation, while lowering the incidence and severity of graft-vs.-host disease (GVHD). Copyright 2001 Wiley-Liss, Inc.

Review of studies of polymorphic blood systems in the Aymara indigenous population from Bolivia, Peru, and Chile.

PubMed

Dittmar, M

1995-12-01

A review was made of all studies available from the literature referring to polymorphic blood systems of South American Aymara Indians. 33 original papers published up to 1990 covering a period of 45 years were summarized. Aymara samples were considered from a total of 55 localities in Bolivia, Peru, and Chile. Gene frequencies were tabulated for 21 polymorphic genetic systems comprising blood groups (AB0, MNSs, P, Rh, Lu, K, Le, Fy, Jk, Di), erythrocyte enzyme groups (AcP, 6PGD, PGM1, AK, ADA, EsD), and plasma protein groups (Hp, Tf, Gc, Gm, Km). Weighted average and range over all Aymara samples were computed for each blood system and compared with corresponding mean value and range in South Amerindians in general. Gene frequency distribution in the Aymara population shows ranges of different orders of magnitude in the 21 blood systems, some of them varying widely. Nevertheless the average gene frequencies for the Aymara are well within the range of values reported for South American Indian populations. The assessment of blood systems in the Aymara revealed that information concerning the Lutheran and HLA systems is scarce or nil up to now. Further studies are needed, especially from Peru on erythrocyte enzyme systems, in order to obtain a more complete picture on the variation of blood system polymorphisms in the Aymara population.

Expression of the GnRH and GnRH receptor (GnRH-R) genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland of anestrous and luteal phase ewes.

PubMed

Ciechanowska, Magdalena; Lapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

2008-11-01

Data exists showing that seasonal changes in the innervations of GnRH cells in the hypothalamus and functions of some neural systems affecting GnRH neurons are associated with GnRH release in ewes. Consequently, we put the question as to how the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland is reflected with LH secretion in anestrous and luteal phase ewes. Analysis of GnRH gene expression by RT-PCR in anestrous ewes indicated comparable levels of GnRH mRNA in the preoptic area, anterior and ventromedial hypothalamus. GnRH-R mRNA at different concentrations was found throughout the preoptic area, anterior and ventromedial hypothalamus, stalk/median eminence and in the anterior pituitary gland. The highest GnRH-R mRNA levels were detected in the stalk/median eminence and in the anterior pituitary gland. During the luteal phase of the estrous cycle in ewes, the levels of GnRH mRNA and GnRH-R mRNA in all structures were significantly higher than in anestrous ewes. Also LH concentrations in blood plasma of luteal phase ewes were significantly higher than those of anestrous ewes. In conclusion, results from this study suggest that low expression of the GnRH and GnRH-R genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland, amongst others, may be responsible for a decrease in LH secretion and the anovulatory state in ewes during the long photoperiod.

The Evolving Role of Lyophilized Plasma in Remote Damage Control Resuscitation in the French Armed Forces Health Service

DTIC Science & Technology

2013-01-01

severely bleeding combat casualties with the following interventions: tourniquets applied immediately in the field, hemo- static dressings, tranexamic ... acid within the first 3 hours, transfusion of FLYP and RBCs in a 1:1 ratio, fresh whole blood (FWB) use, correction of acidosis with bicarbonate...products: hemoglobin, ABO-Rh-Kell grouping, HIV 1 and 2 antibodies and nucleic acid testing (NAT), HCV antibodies and NAT, hepatitis B virus antigen and

Mitochondrial distribution and activity in human mature oocytes: gonadotropin-releasing hormone agonist versus antagonist for pituitary down-regulation.

PubMed

Dell'Aquila, Maria Elena; Ambruosi, Barbara; De Santis, Teresa; Cho, Yoon Sung

2009-01-01

To analyze the effects of GnRH agonists versus antagonists on mitochondrial distribution and activity in human mature oocytes. Randomized research experimental study. Academic basic research laboratory and hospital-based fertility center. Two hundred twenty-five supernumerary mature oocytes from 44 patients. Fluorescent staining and confocal laser scanning microscopy on oocytes after the use of either GnRH agonist (group A) or GnRH antagonist (group B). Oocyte mitochondrial distribution pattern and activity using MitoTracker Orange CMTM Ros. More oocytes showing polarized mitochondrial distribution pattern were found in group A than in group B (35% vs. 14%). In group B, hCG rather than GnRH agonist, for ovulation induction, resulted in more oocytes showing heterogeneous (57% vs. 14%), in particular polarized (24% vs. 0) mitochondrial distribution. In groups A and B, fluorescence intensity did not vary according to mitochondrial distribution pattern. However, fluorescence intensity was higher in oocytes with polarized and large granules configurations in group B compared to group A. The GnRH agonist and antagonist may have different effects on oocyte mitochondrial distribution pattern and activity. The GnRH antagonist may induce mitochondrial hyperactivity, which may be detrimental to the oocyte.

Complication Rates in Posterior Lumbar Interbody Fusion (PLIF) Surgery With Human Bone Morphogenetic Protein 2: Medicare Population.

PubMed

Alobaidaan, Raed; Cohen, Jeremiah R; Lord, Elizabeth L; Buser, Zorica; Yoon, S Tim; Youssef, Jim A; Park, Jong-Beom; Brodke, Darrel S; Wang, Jeffrey C; Meisel, Hans-Joerg

2017-12-01

Retrospective cohort study among Medicare beneficiaries who underwent posterior lumbar interbody fusion (PLIF) surgery. To identify the complication rates associated with the use of bone morphogenetic protein 2 (BMP2) in PLIF. Human BMP2 is commonly used in the "off-label" manner for various types of spine fusion procedures, including PLIF. However, recent studies have reported potential complications associated with the recombinant human BMP2 (rhBMP2) use in the posterior approach. Medicare records within the PearlDiver database were queried for patients undergoing PLIF procedure with and without rhBMP2 between 2005 and 2010. We evaluated complications within 1 year postoperatively. Chi-square was used to compare the complication rates between the 2 groups. A total of 8609 patients underwent PLIF procedure with or without rhBMP2. Individual complication rates in the rhBMP2 group ranged from 0.45% to 7.68% compared with 0.65% to 10.99 in the non-rhBMP2 group. Complication rates for cardiac, pulmonary, lumbosacral neuritis, infection, wound, and urinary tract (include acute kidney failure and post-operative complications) were significantly lower in the rhBMP2 group ( P < .05). There was no difference in the rates of central nervous system complications or radiculitis between the 2 groups. Our data showed that the patients who received rhBMP2 had lower complication rates compared to the non-rhBMP2 group. However, use of rhBMP2 was associated with a higher rate of pseudarthrosis. We did not observe any difference in radiculitis and central nervous system complications between the groups.

Complication Rates in Posterior Lumbar Interbody Fusion (PLIF) Surgery With Human Bone Morphogenetic Protein 2: Medicare Population

PubMed Central

Alobaidaan, Raed; Cohen, Jeremiah R.; Lord, Elizabeth L.; Yoon, S. Tim; Youssef, Jim A.; Park, Jong-Beom; Brodke, Darrel S.; Wang, Jeffrey C.; Meisel, Hans-Joerg

2017-01-01

Study Design: Retrospective cohort study among Medicare beneficiaries who underwent posterior lumbar interbody fusion (PLIF) surgery. Objective: To identify the complication rates associated with the use of bone morphogenetic protein 2 (BMP2) in PLIF. Human BMP2 is commonly used in the “off-label” manner for various types of spine fusion procedures, including PLIF. However, recent studies have reported potential complications associated with the recombinant human BMP2 (rhBMP2) use in the posterior approach. Methods: Medicare records within the PearlDiver database were queried for patients undergoing PLIF procedure with and without rhBMP2 between 2005 and 2010. We evaluated complications within 1 year postoperatively. Chi-square was used to compare the complication rates between the 2 groups. Results: A total of 8609 patients underwent PLIF procedure with or without rhBMP2. Individual complication rates in the rhBMP2 group ranged from 0.45% to 7.68% compared with 0.65% to 10.99 in the non-rhBMP2 group. Complication rates for cardiac, pulmonary, lumbosacral neuritis, infection, wound, and urinary tract (include acute kidney failure and post-operative complications) were significantly lower in the rhBMP2 group (P < .05). There was no difference in the rates of central nervous system complications or radiculitis between the 2 groups. Conclusion: Our data showed that the patients who received rhBMP2 had lower complication rates compared to the non-rhBMP2 group. However, use of rhBMP2 was associated with a higher rate of pseudarthrosis. We did not observe any difference in radiculitis and central nervous system complications between the groups. PMID:29238641

Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia.

PubMed

Kocherlakota, P; La Gamma, E F

1997-07-01

To determine whether adjunctive therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival compared with conventional therapy in a phase I/II-type trial. An intravenous infusion of rhG-CSF (10 microg/kg/d x 3 d) was administered to 14 septic neutropenic neonates. Neutrophilic responses and outcome of these neonates were compared with 11 concurrently treated, retrospectively selected, case-matched control septic patients identified by using a search of medical records coded for sepsis with neutropenia (>/=24 hours). Seven neonates with early-onset sepsis with neutropenia at birth and seven neonates with late-onset sepsis plus neutropenia (all with necrotizing enterocolitis) were entered in the rhG-CSF treatment group. Results were compared with a conventional therapy control group (five early onset, six late onset). No significant differences existed in the birth weight, gestational age, use of antibiotic therapy, magnitude of respiratory support, severity of metabolic acidosis, use of vasopressors, or other supportive therapy between the two groups. In the rhG-CSF-treated group and in the conventionally treated control group, the absolute neutrophil count (ANC) (mean +/- SEM) was 585 +/- 138 and 438 +/- 152, respectively. The ANC increased to more than baseline in the rhG-CSF-treated group by 10-fold versus 2-fold at 24 hours, 18-fold versus 4-fold at 48 hours, 24-fold versus 5-fold at 72 hours (significant by one-way analysis of variance in the rhG-CSF group only), and 29-fold versus 16-fold at 7 to 10 days when compared with the conventional therapy group. There were no nonresponders in the rhG-CSF group by 24 hours after the first dose of study drug. Monocyte cell counts also increased significantly in both groups by 7 days after entry into this protocol but remained within normal range for age. No clinically significant effect on lymphocytes, erythrocytes, or platelet counts was noted. Thirteen patients in the rhG-CSF-treated group (92%; 13 out of 14) and five in the conventionally treated group (55%; 5 out of 11) survived to 28 days after the onset of the signs of sepsis. No adverse effects were noted in the rhG-CSF-treated group. rhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonates. This finding suggests that rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow suppression or neutrophil consumption. Future randomized trials are needed to validate the beneficial effects of rhG-CSF and to determine whether any significant side effects of therapy exist.

Thyroid stimulation with recombinant human thyrotropin in healthy cats, cats with non-thyroidal illness and in cats with low serum thyroxin and azotaemia after treatment of hyperthyroidism.

PubMed

van Hoek, Ingrid M; Vandermeulen, Eva; Peremans, Kathelijne; Daminet, Sylvie

2010-02-01

This study investigated the recombinant human thyrotropin (rhTSH) stimulation test in healthy cats (group 1), cats with non-thyroidal illness (group 2) and cats with low serum total T(4) (TT(4)) and azotaemia after (131)I treatment (group 3). Serum TT(4) responses and thyroidal pertechnetate uptake after administration of 25 microg rhTSH IV were assessed. Baseline serum TT(4) was significantly lower in group 3 compared with group 1, but not between other group pairs. Serum TT(4) increased significantly in groups 1 and 2 but not in group 3 after rhTSH administration. Post-rhTSH serum TT(4) concentrations differed significantly between groups 1 and 3 and groups 2 and 3, but not between groups 1 and 2. Thyroid/salivary gland uptake ratio (T/S uptake ratio) differed only significantly between groups 1 and 3. Stimulation with rhTSH is valuable to differentiate euthyroidism from iatrogenic hypothyroidism in cats. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Age and body composition influence TSH concentrations after administration of rhTSH.

PubMed

Holthausen, F F; von Müller, F; Happel, C; Kranert, W T; Grünwald, F

2015-01-01

Previous studies listed body surface area (BSA), lean body mass (LBM), and age as modifying factors on the TSH concentrations after administration of recombinant human thyrotropin (rhTSH). The purpose of this study was to identify the main modifying factors on serum TSH levels and to compare the stimulation via single rhTSH injection after a short thyroid hormone withdrawal (THW) with that of the standard stimulating protocol. 106 patients with differentiated thyroid cancer (DTC) undergoing radioiodine therapy (RIT) after rhTSH administration were obtained through chart review. Two groups were evaluated: Group I was treated with a single rhTSH administration after two weeks of T3 therapy followed by one week of THW. Group II was stimulated according to the international standard protocol via rhTSH injections for two consecutive days. Serum TSH concentrations were documented prior to rhTSH administration (day 1 TSH), one day after (day 3 TSH) and 3-6 days after (mean 4.2 days, day 6 TSH) the last rhTSH injection. The following data was collected: age, gender, weight, height, BMI, LBM, BSA, residual thyroid tissue, CRP, creatinine, GFR, liver enzymes, alkaline phosphatase, cholesterol, and triglycerides. Group I: Age combined with anthropometric factors like BMI (TSH increase and day 6 TSH), BSA (TSH decrease), and gender (day 6 TSH) are the main modifying factors on serum TSH concentrations after rhTSH administration. Group II: Age and lean body mass (LBM) showed a significant impact on day 3 TSH, TSH increase (day 3-day 1), and TSH decrease (day 6-day 3). Day 6 TSH was found to be influenced by GFR (group II). Age and anthropometric parameters have significant independent influence on TSH concentrations after rhTSH injection in both groups. Anthropometric parameters (BSA, LBM) and demographic parameters (female gender) show strong influence on TSH concentrations. Further research should be conducted to examine the influence of body compartments on TSH levels through measuring total body water.

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles.

PubMed

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1).

[RHD variant in RhD/-/ mother with anti-D makes noninvasive fetal RHD genotyping impossible].

PubMed

Orzińska, Agnieszka; Engel, Karina; Łakomy, Magdalena; Smolarczyk-Wodzyńska, Justyna; Lipińska, Anna; Pelc-Kłopotowska, Monika; Brojer, Ewa

2009-10-01

Noninvasive fetal RHD genotyping from maternal plasma of RhD(/-) pregnant women of Caucasian race may be used for predicting the risk of hemolytic disease because the RHD gene is usually absent in such populations. If detected in plasma of such women, the RHD gene originates from the RhD(+) fetus. The number of fetal copies of the gene in maternal plasma is extremely small. In the presented case of the RhD(/-) pregnant woman with anti-D it was impossible to give a fetal RHD result due to mother's RHD(+) genotype. The fetal RHD was determined from amniocytes. to present the difficulties related to the interpretation of results of invasive and noninvasive procedures. whole blood, plasma and amniotic fluid of the RhD(-) woman with anti-D (14 week of pregnancy) as well as whole blood of the newborn. RHD and RHCE*c were genotyped by real-time PCR in DNA isolated from maternal plasma and amniocytes and the RHD and d-genotypes were tested by SSP methods in DNA isolated from whole blood and amniocytes. RHD and RHCE*c were detected in DNA isolated from plasma. The high level of RHD suggested its origin from the mother's DNA therefore it was impossible to determine the fetal RHD. The d-little test identified a RHD(IVS3+ 1G>A) variant in the mother's genome. A weak signal of real-time PCR for the RHD was obtained in amniocytes but the RHD was not detected by SSP. The RHCE*c was detected by both methods. Results were inconclusive; the fetal RHD status remained unknown. The child was RhD(-) with RHD in its DNA undetected by either method. 1/The RHD(IVS3+ 1G>A) variant in the RhD(-) mother precluded formal noninvasive fetal RHD genotyping. 2/Real-time PCR is too sensitive for amniocyte testing and may lead to false results as it detects trace maternal DNA in amniotic fluid. 3/The frequency of RHD(IVS3+1G>A) occurrence in Poland requires further studies.

Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells

NASA Technical Reports Server (NTRS)

Ichiki, A. T.; Gibson, L. A.; Jago, T. L.; Strickland, K. M.; Johnson, D. L.; Lange, R. D.; Allebban, Z.

1996-01-01

The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

PubMed

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Screening and identification of RhD antigen mimic epitopes from a phage display random peptide library for the serodiagnosis of haemolytic disease of the foetus and newborn.

PubMed

Wang, Jiao; Song, Jingjing; Zhou, Shuimei; Fu, Yourong; Bailey, Jeffrey A; Shen, Changxin

2018-01-16

Identification of RhD antigen epitopes is a key component in understanding the pathogenesis of haemolytic disease of the foetus and newborn. Research has indicated that phage display libraries are useful tools for identifying novel mimic epitopes (mimotopes) which may help to determine antigen specificity. We selected the mimotopes of blood group RhD antigen by affinity panning a phage display library using monoclonal anti-D. After three rounds of biopanning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and then sent for sequencing and peptides synthesis. Next, competitive ELISA and erythrocyte haemagglutination inhibition tests were carried out to confirm the inhibitory activity of the synthetic peptide. To evaluate the diagnostic performance of the synthetic peptide, a diagnostic ELISA was examined. Fourteen of 35 phage clones that were chosen randomly from the titering plate were considered to be positive. Following DNA sequencing and translation, 11 phage clones were found to represent the same peptide - RMKMLMMLMRRK (P4) - whereas each of the other three clones represented a unique peptide. Through the competitive ELISA and erythrocyte haemagglutination inhibition tests, the peptide (P4) was verified to have the ability to mimic the RhD antigen. The diagnostic ELISA for P4 proved to be sensitive (82.61%) and specific (88.57%). This study reveals that the P4 peptide can mimic RhD antigen and paves the way for the development of promising targeted diagnostic and therapeutic platforms for haemolytic disease of the foetus and newborn.

[Preparation of vanilline cross-linked rhBMP-2/chitosan microspheres and its effect on mesenchymal stem cells].

PubMed

Wu, Gui; Wang, Hai; Qiu, Guixing; Yu, Xin; Su, Xinlin; Ma, Pei; Yin, Bo; Wu, Zhihong

2015-06-02

To prepare rhBMP-2/chitosan microspheres (rhBMP-2 CMs) with vanilline as a cross-linking reagent and study the biocompatibility and drug release characteristic of microspheres in vitro. Emulsion cross-linking method was utilized to prepare rhBMP-2 CMs, Scanning electron microscope (SEM) was used to observe the microstructure of microspheres.Leaching solution of microspheres and blank culture medium were designated as experimental and control groups respectively. Both groups were cultured with human mesenchymal stem cells (hMSCs) to determine its cytotoxicity and its effect on the proliferation of hMSCs. Dynamic immersion method was used to examine the in vitro release characteristic of rhBMP-2. And the alkaline phosphatase (ALP) activity of hMSCs was determined to reveal the bioactivity of released rhBMP-2. The rhBMP-2 CMs were spherical under SEM.After treating with leaching solution for 24 and 48 h, there was no inter-group statistical difference in optical density (OD) values at both timepoints (24 h:0.72 ± 0.07 vs 0.73 ± 0.05, P > 0.05; 48 h:1.19 ± 0.11 vs 1.27 ± 0.06, P > 0.05). After culturing with leaching solution for 1, 3 and 7 days, the number of cells increased with time for both groups. And the OD values were not statistically different at each timepoint. Five milligram rhBMP-2 CMs soaked for 19 days with a gradual release of rhBMP-2. The concentration of rhBMP-2 was 216.1 ± 20.0 ng/ml at Day 19. At Days 3 and 7, the ALP activities of hMSCs were (0.50 ± 0.07) and (0.68 ± 0.06) µmol pNPP·min⁻¹·mg⁻¹ protein respectively and both were higher than that of blank culture medium group (0.14 ± 0.01) (P < 0.05). With an excellent biocompatibility, rhBMP-2 CMs may be an ideal carrier for control-released rhBMP-2 and encapsulated rhBMP-2 remains bioactive.

Evaluation of recombinant human thyroid-stimulating hormone to test thyroid function in dogs suspected of having hypothyroidism.

PubMed

Boretti, Felicitas S; Sieber-Ruckstuhl, Nadja S; Favrot, Claude; Lutz, Hans; Hofmann-Lehmann, Regina; Reusch, Claudia E

2006-12-01

To evaluate the use of recombinant human (rh) thyroid-stimulating hormone (TSH) in dogs with suspected hypothyroidism. 64 dogs with clinical signs of hypothyroidism. Dogs received rhTSH (75 microg/dog, IV) at a dose independent of their body weight. Blood samples were taken before and 6 hours after rhTSH administration for determination of total serum thyroxine (T(4)) concentration. Dogs were placed into 1 of 3 groups as follows: those with normal (ie, poststimulation values indicative of euthyroidism), unchanged (ie, poststimulation values indicative of hypothyroidism; no thyroid gland stimulation), or intermediate (ie, poststimulation values between unchanged and normal values) post-TSH T(4) concentrations. Serum canine TSH (cTSH) concentration was determined in prestimulation serum (ie, before TSH administration). 14, 35, and 15 dogs had unchanged, normal, and intermediate post-TSH T(4) concentrations, respectively. Basal T(4) and post-TSH T(4) concentrations were significantly different among groups. On the basis of basal serum T(4) and cTSH concentrations alone, 1 euthyroid (normal post-TSH T(4), low basal T(4), and high cTSH concentrations) and 1 hypothyroid dog (unchanged post-TSH T(4) concentration and low to with-in reference range T(4) and cTSH concentrations) would have been misinterpreted as hypothyroid and euthyroid, respectively. Nine of the 15 dogs with intermediate post-TSHT(4) concentrations had received medication known to affect thyroid function prior to the test, and 2 of them had severe nonthyroidal disease. The TSH-stimulation test with rhTSH is a valuable diagnostic tool to assess thyroid function in selected dogs in which a diagnosis of hypothyroidism cannot be based on basal T(4) and cTSH concentrations alone.

Biocompatible coupling of therapeutic fusion proteins to human erythrocytes

PubMed Central

Villa, Carlos H.; Pan, Daniel C.; Johnston, Ian H.; Greineder, Colin F.; Walsh, Landis R.; Hood, Elizabeth D.; Cines, Douglas B.; Poncz, Mortimer; Siegel, Don L.

2018-01-01

Carriage of drugs by red blood cells (RBCs) modulates pharmacokinetics, pharmacodynamics, and immunogenicity. However, optimal targets for attaching therapeutics to human RBCs and adverse effects have not been studied. We engineered nonhuman-primate single-chain antibody fragments (scFvs) directed to human RBCs and fused scFvs with human thrombomodulin (hTM) as a representative biotherapeutic cargo (hTM-scFv). Binding fusions to RBCs on band 3/glycophorin A (GPA; Wright b [Wrb] epitope) and RhCE (Rh17/Hr0 epitope) similarly endowed RBCs with hTM activity, but differed in their effects on RBC physiology. scFv and hTM-scFv targeted to band 3/GPA increased membrane rigidity and sensitized RBCs to hemolysis induced by mechanical stress, while reducing sensitivity to hypo-osmotic hemolysis. Similar properties were seen for other ligands bound to GPA and band 3 on human and murine RBCs. In contrast, binding of scFv or hTM-scFv to RhCE did not alter deformability or sensitivity to mechanical and osmotic stress at similar copy numbers bound per RBCs. Contrasting responses were also seen for immunoglobulin G antibodies against band 3, GPA, and RhCE. RBC-bound hTM-scFv generated activated protein C (APC) in the presence of thrombin, but RhCE-targeted hTM-scFv demonstrated greater APC generation per bound copy. Both Wrb- and RhCE-targeted fusion proteins inhibited fibrin deposition induced by tumor necrosis factor-α in an endothelialized microfluidic model using human whole blood. RhCE-bound hTM-scFv more effectively reduced platelet and leukocyte adhesion, whereas anti-Wrb scFv appeared to promote platelet adhesion. These data provide a translational framework for the development of engineered affinity ligands to safely couple therapeutics to human RBCs. PMID:29365311

A phase I study of recombinant human leukemia inhibitory factor in patients with advanced cancer.

PubMed

Gunawardana, Dishan H; Basser, Russell L; Davis, Ian D; Cebon, Jonathan; Mitchell, Paul; Underhill, Craig; Kilpatrick, Trevor J; Reardon, Katrina; Green, Michael D; Bardy, Peter; Amor, Pene; Crump, David; Ng, Siobhan; Nation, Roger L; Begley, C Glenn

2003-06-01

Leukemia inhibitory factor (LIF) is a pleiotropic molecule of the interleukin 6 family of cytokines. We aimed to examine the safety, pharmacokinetics, and biological effects of recombinant human LIF (rhLIF, emfilermin) in patients with advanced cancer. In stage 1 of the study, 34 patients received rhLIF or placebo (3:1 ratio) at doses of 0.25-16.0 micro g/kg/day or 4.0 micro g/kg three times daily for 7 days. In stage 2, 40 patients received rhLIF or placebo, either once daily for 14 days commencing the day after chemotherapy (0.25-8.0 micro g/kg/day) or for 7 days commencing the day before chemotherapy (4.0 micro g/kg three times daily). The chemotherapy was cisplatin 75 mg/m(2) and paclitaxel 135 mg/m(2). In stage 1, platelet counts increased in most patients, including those who received placebo. Blood progenitor cells increased in response to rhLIF. In stage 2, platelet recovery to baseline levels was earlier for patients receiving higher doses of rhLIF (>/=4.0 micro g/kg/day; P = 0.02). The neutrophil nadir after chemotherapy was less severe in patients receiving >/=4.0 micro g/kg/day of rhLIF. In stages 1 and 2, increases in C reactive protein were seen at higher doses. Several patients developed evidence of autonomic dysfunction, in particular impotence and episodic hypotension. The dose-limiting toxicities were hypotension and rigors. Pharmacokinetic studies demonstrated a short half-life (1-5 h) independent of dose. We demonstrated a biological effect of rhLIF on blood progenitor cells, C reactive protein levels, and hemopoietic recovery after chemotherapy.

Clinical observation of the therapeutic effects of pegylated recombinant human granulocyte colony-stimulating factor in patients with concurrent chemoradiotherapy-induced grade IV neutropenia

PubMed Central

WU, FENG-PENG; WANG, JUN; WANG, HUI; LI, NA; GUO, YIN; CHENG, YUN-JIE; LIU, QING; YANG, XIANG-RAN

2015-01-01

The aim of the present study was to investigate the efficacy and side-effects of preventive treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on concurrent chemoradiotherapy-induced grade IV neutropenia and to provide a rational basis for its clinical application. A total of 114 patients with concurrent chemoradiotherapy-induced grade IV neutropenia were enrolled. A randomized approach was used to divide the patients into an experimental group and a control group. The experimental group included three subgroups, namely a P-50 group, P-100 group and P + R group. The P-50 group had 42 cases, which were given a single 50-μg/kg subcutaneous injection of PEG-rhG-CSF. The P-100 group had 30 cases, which received a single 100-μg/kg subcutaneous injection of PEG-rhG-CSF. The P + R group comprised 22 cases, which were given a single 50-μg/kg subcutaneous injection of PEG-rhG-CSF and rhG-CSF 5 μg/kg/day; when the absolute neutrophil count (ANC) was ≥2.0×109/l, the administration of rhG-CSF was stopped. The control group (RC group) comprised 20 patients, who received rhG-CSF 5 μg/kg/day by subcutaneous injection until the ANC was ≥2.0×109/l. Changes in the neutrophil proliferation rate and ANC values over time, the neutropenic symptom remission time and incidence of adverse drug reactions were analyzed statistically in each group of patients. In the experimental group, the neutrophil proliferation rate and ANC values were significantly higher than those in the control group; the clinical effects began 12–24 h after treatment in the experimental group, and indicated that the treatment improved neutropenia in ~48 h after treatment. There was no significant difference in the neutrophil proliferation rate and ANC values between the P-50 and P+R groups. In the experimental group, the remission time of neutropenia-induced fever and muscle pain after administration was significantly shorter than that in the control group, with a statistically significant difference (P<0.05). The adverse drug reaction rates showed no significant difference between the experimental group and the control group. PEG-rhG-CSF had good efficacy and safety in the treatment of concurrent chemotherapy-induced grade IV neutropenia. For the treatment of concurrent chemotherapy-induced grade IV neutropenia, a single subcutaneous injection of 50 μg/kg PEG-rhG-CSF is the recommended dose. The effects begin at 12–24 h; if the ANC values are not significantly improved during this time, no supplementary administration of rhG-CSF is necessary. PMID:25667625

Delayed hemolytic transfusion reaction presenting as a painful crisis in a patient with sickle cell anemia.

PubMed

Fabron, A; Moreira, G; Bordin, J O

1999-01-07

Patients with sickle cell anemia (SCA) are frequently transfused with red blood cells (RBC). Recently we reported that the calculated risk of RBC alloimmunization per transfussed unit in Brazilian patients with SCA is 1.15%. We describe a delayed hemolytic transfusion reaction (DHTR) presenting as a painful crisis in a patient with SCA. A 35-year-old Brazilian female with homozygous SCA was admitted for a program of partial exchange transfusion prior to cholecystectomy. Her blood group was O RhD positive and no atypical RBC alloantibody was detected using the indirect antiglobulin technique. Pre-transfusional hemoglobin (Hb) was 8.7 g/dL and isovolumic partial exchange transfusion was performed using 4 units of ABO compatible packed RBC. Five days after the last transfusion she developed generalized joint pain and fever of 39 degrees C. Her Hb level dropped from 12.0 g/dL to 9.3 g/dL and the unconjugated bilirrubin level rose to 27 mmol/L. She was jaundiced and had hemoglobinuria. Hemoglobin electrophoresis showed 48.7% HbS, 46.6% HbA1, 2.7% HbA2, and 2.0% HbF. The patient's extended RBC phenotype was CDe, K-k+, Kp(a-b+), Fy(a-b-), M+N+s+, Le(a+b-), Di(a-). An RBC alloantibody with specificity to the Rh system (anti-c, titer 1:16.384) was identified by the indirect antiglobulin test. The Rh phenotype of the RBC used in the last packed RBC transfusion was CcDEe. The patient was discharged, asymptomatic, 7 days after admission.

Antibody screening & identification in the general patient population at a tertiary care hospital in New Delhi, India.

PubMed

Makroo, Raj Nath; Bhatia, Aakanksha; Hegde, Vikas; Chowdhry, Mohit; Thakur, Uday Kumar; Rosamma, N L

2014-09-01

The development of alloantibodies can significantly complicate transfusion therapy and results in difficulties in cross-matching of blood. Most literature on alloimmunization is limited to multitransfused individuals, with very few studies on the general hospital patients. This study was aimed at assessing the frequency and type of unexpected red cell antibodies in the general patient population at a multispecialty tertiary care centre in New Delhi, India. The results of 49,077 antibody screening tests carried out on patients, from January 2009 to December 2012 were analyzed. The clinical and transfusion records were reviewed. The data were compiled and statistically analysed. A total of 49,077 (29,917; 60.96% males and 19,160; 39.04% females) patient samples were screened for the presence of unexpected antibodies. Antibody screening was positive in 403 patients (0.82%). In the serum samples of 164 patients only autoantibodies were identified, 27 revealed autoantibodies with one or more underlying alloantibodies, while 212 patients had only alloantibody/ies in their serum. The overall alloimmunization rate was 0.49 per cent. Antibodies against the Rh system were the most frequent (64.1%), the most common alloantibody identified being anti E (37.2%), followed by anti D (19.2%). Since clinically significant antibodies are frequently detected in our patient population, antibody screening and if required, identification is the need of the hour. Since antibodies against the common Rh and Kell blood group antigens are the most frequent, provision of Rh and Kell matched red cells may be of protective value.

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles

PubMed Central

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

Background: This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. Materials and Methods: In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. Results: There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). Conclusion: According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1). PMID:24520450

Sestrin2 Induced by Hypoxia Inducible Factor 1 alpha protects the Blood-Brain Barrier via Inhibiting VEGF after Severe Hypoxic-Ischemic Injury in Neonatal Rats

PubMed Central

Shi, Xudan; Doycheva, Desislava Met; Xu, Liang; Tang, Jiping; Yan, Min; Zhang, John H

2016-01-01

Objective Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injury. Methods Rat pups underwent common carotid artery ligation followed by either 150 min (severe model) or 100 min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) were used to examine their roles on BBB permeability. Results Rats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability. Conclusions rh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α’s effects as a prodeath or prosurvival signal were influenced by the severity of HI injury. PMID:27425892

Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases. allo-PBPCT Spanish Group.

PubMed

Urbano-Ispizua, A; Solano, C; Brunet, S; Hernández, F; Sanz, G; Alegre, A; Petit, J; Besalduch, J; Vivancos, P; Díaz, M A; Moraleda, J M; Carreras, E; Ojeda, E; de la Rubia, J; Benet, I; Domingo-Albós, A; García-Conde, J; Rozman, C

1996-07-01

The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).

Rapid RHD Zygosity Determination Using Digital PCR.

PubMed

Sillence, Kelly A; Halawani, Amr J; Tounsi, Wajnat A; Clarke, Kirsty A; Kiernan, Michele; Madgett, Tracey E; Avent, Neil D

2017-08-01

Paternal zygosity testing is used for determining homo- or hemizygosity of RHD in pregnancies that are at a risk of hemolytic disease of the fetus and newborn. At present, this is achieved by using real-time PCR or the Rhesus box PCR, which can be difficult to interpret and unreliable, particularly for black African populations. DNA samples extracted from 53 blood donors were analyzed using 2 multiplex reactions for RHD -specific targets against a reference ( AGO1 ) 2 to determine gene dosage by digital PCR. Results were compared with serological data, and the correct genotype for 2 discordant results was determined by long-range PCR (LR-PCR), next-generation sequencing, and conventional Sanger sequencing. The results showed clear and reliable determination of RHD zygosity using digital PCR and revealed that 4 samples did not match the serologically predicted genotype. Sanger sequencing and long-range PCR followed by next-generation sequencing revealed that the correct genotypes for samples 729M and 351D, which were serologically typed as R 1 R 2 (DCe/DcE), were R 2 r' (DcE/dCe) for 729M and R 1 r″ (DCe/dcE), R 0 r y (Dce/dCE), or R Z r (DCE/dce) for 351D, in concordance with the digital PCR data. Digital PCR provides a highly accurate method to rapidly define blood group zygosity and has clinical application in the analysis of Rh phenotyped or genotyped samples. The vast majority of current blood group genotyping platforms are not designed to define zygosity, and thus, this technique may be used to define paternal RH zygosity in pregnancies that are at a risk of hemolytic disease of the fetus and newborn and can distinguish between homo- and hemizygous RHD -positive individuals. © 2017 American Association for Clinical Chemistry.

Empirical constraints on partitioning of platinum group elements between Cr-spinel and primitive terrestrial magmas

NASA Astrophysics Data System (ADS)

Park, Jung-Woo; Kamenetsky, Vadim; Campbell, Ian; Park, Gyuseung; Hanski, Eero; Pushkarev, Evgeny

2017-11-01

Recent experimental studies and in situ LA-ICP-MS analysis on natural Cr-spinel have shown that Rh and IPGEs (Ir-group platinum group elements: Ru, Ir, Os) are enriched in the lattice of Cr-spinel. However, the factors controlling the partitioning behaviour of these elements are not well constrained. In this study, we report the Rh, IPGE, and trace element contents in primitive Cr-spinel, measured by LA-ICP-MS, from nine volcanic suites covering various tectonic settings including island arc picrites, boninites, large igneous province picrites and mid-ocean ridge basalts. The aim is to understand the factors controlling the enrichment of Rh and IPGEs in Cr-spinels, to estimate empirical partition coefficients between Cr-spinel and silicate melts, and to investigate the role of Cr-spinel fractional crystallization on the PGE geochemistry of primitive magmas during the early stages of fractional crystallization. There are systematic differences in trace elements, Rh and IPGEs in Cr-spinels from arc-related magmas (Arc Group Cr-spinel), intraplate magmas (Intraplate Group Cr-spinel), and mid-ocean ridge magmas (MORB Group Cr-spinel). Arc Group Cr-spinels are systematically enriched in Sc, Co and Mn and depleted in Ni compared to the MORB Group Cr-spinels. Intraplate Group Cr-spinels are distinguished from the Arc Group Cr-spinels by their high Ni contents. Both the Arc and Intraplate Group Cr-spinels have total Rh and IPGE contents of 22-689 ppb whereas the MORB Group Cr-spinels are depleted in Rh and IPGE (total < 20 ppb). Palladium and Pt contents are below detection limit for all of the studied Cr-spinels (<1-5 ppb). The time-resolved spectra of LA-ICP-MS data for Cr-spinels mostly show constant count rates for trace element and Rh and IPGEs, suggesting homogeneous distribution of these elements in Cr-spinels. The PGE spikes observed in several Cr-spinels were interpreted to be PGE-bearing mineral inclusions and excluded from calculating the PGE contents of the Cr-spinels. On primitive mantle normalized diagrams the Arc Group Cr-spinels are characterized by a fractionated pattern with high Rh and low Os. The Intraplate Group Cr-spinels show flat patterns with positive Ru anomalies. Our results, together with the experimental and empirical data from previous studies, show that PGE patterns of Cr-spinel largely mimic that of the rock in which they are found, and that Rh, Ir and Os contents increase with increasing Fe3+ contents (i.e. magnetite component) in Cr-spinel, although Ru does not. These observations suggest that the enrichment of Rh and IPGEs in Cr-spinel is controlled by a combination of the Rh and IPGE contents in parental melts and the magnetite component of the spinel. Empirical partition coefficients (D) for Rh and IPGEs between Cr-spinels and silicate melts were calculated using the Rh and IPGE contents of the Cr-spinel and their host volcanic rocks after subtracting the accumulation effect of Cr-spinel. The D values for the Intraplate and MORB Group Cr-spinels increase with increasing magnetite component in Cr-spinel and range from 6 to 512, which is consistent with previously reported experimental and empirical values. In contrast, the Arc Group Cr-spinels have significantly higher D values (e.g. up to ∼3700 for Ru) than those of the Intraplate and MORB Group at the same magnetite concentration in the Cr-spinel, suggesting Rh and IPGEs dissolved in silicate melt have stronger affinity for Cr spinel under arc magma conditions than in intraplate magmas. This may be partly attributed to the low temperature of arc magmas relative to intraplate magmas, which leads to the Arc Group Cr-spinels having more octahedral sites at the same magnetite components than the Intraplate Group Cr-spinels. Because of significantly higher D values for the Arc Group Cr-spinels, compared with the Intraplate Group and MORB Group spinels, fractional crystallization of Cr-spinel will more efficiently fractionate Rh and IPGE from Pd and Pt in arc systems than in intraplate and MORB systems, which accounts for the highly fractionated PGE patterns in arc basalts.

Production of human monoclonal IgG antibodies against Rhesus (D) antigen.

PubMed Central

Bron, D; Feinberg, M B; Teng, N N; Kaplan, H S

1984-01-01

An Epstein-Barr virus (EBV)-transformed human B-cell line ( LB4r ) producing anti-Rhesus [Rho(D) antigen] antibody was fused with a non-immunoglobulin-producing mouse-human heteromyeloma ( SHM - D33 ) and selected in hypoxanthine/aminopterin/thymidine medium containing 0.5 microM ouabain. Surviving hybrids found to secrete specific anti-Rho(D) antibody were cloned by limiting dilution. Two clones (D4-B2 and E10-C1) producing high levels (12 and 20 micrograms/ml per 10(6) cells per 24 hr, respectively) of monospecific antibody (IgG3, lambda chain) were selected for expansion and further characterization. Compared to the parental cell line ( LB4r ), these hybridoma cell lines presented several advantages: antibody production was increased 10-fold, cloning efficiency was improved, and the EBV genome was not retained. Antibody production has been stable for greater than 8 months. These human monoclonal anti-Rho(D) antibodies have demonstrated utility in routine blood-group typing. They may also prove useful in the biochemical and genetic characterization of the Rh antigen system. Most important, they offer a source of Rh-immune globulin for the prevention of Rh immunization and alloimmune hemolytic disease of the newborn. Images PMID:6427767

Consequences of increased use of computed tomography imaging for trauma patients in rural referring hospitals prior to transfer to a regional trauma centre.

PubMed

Berkseth, Timothy J; Mathiason, Michelle A; Jafari, Mary Ellen; Cogbill, Thomas H; Patel, Nirav Y

2014-05-01

Computed tomography (CT) plays an integral role in the evaluation and management of trauma patients. As the number of referring hospital (RH)-based CT scanners increased, so has their utilization in trauma patients before transfer. We hypothesized that this has resulted in increased time at RH, image duplication, and radiation dose. A retrospective chart review was completed for trauma activations transferred to an ACS-verified Level II Trauma Centre (TC) during two time periods: 2002-2004 (Group 1) and 2006-2008 (Group 2). 2005 data were excluded as this marked the transition period for acquisition of hospital-based CT scanners in RH. Statistical analysis included t test and χ(2) analysis. P<0.05 was considered significant. 1017 patients met study criteria: 503 in group 1 and 514 in group 2. Mean age was greater in group 2 compared to group 1 (40.3 versus 37.4, respectively; P=0.028). There were 115 patients in group 1 versus 202 patients in group 2 who underwent CT imaging at RH (P<0.001). Conversely, 326 patients in group 1 had CT scans performed at the TC versus 258 patients in group 2 (P<0.001). Mean time at the RH was similar between the groups (117.1 and 112.3min for group 1 and 2, respectively; P=0.561). However, when comparing patients with and without a pretransfer CT at the RH, the median time at RH was 140 versus 67min, respectively (P<0.001). The number of patients with duplicate CT imaging (n=34 in group 1 and n=42 in group 2) was not significantly different between the two time periods (P=0.392). Head CTs comprised the majority of duplicate CT imaging in both time periods (82.4% in group 1 and 90.5% in group 2). Mean total estimated radiation dose per patient was not significantly different between the two groups (group 1=8.4mSv versus group 2=7.8mSv; P=0.192). A significant increase in CT imaging at the RH prior to transfer to the TC was observed over the study periods. No associated increases in mean time at the RH, image duplication at TC, total estimated radiation dose per patient, and mortality rate were observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single and double C-Cl-activation of methylene chloride by P,N-ligand coordinated rhodium complexes.

PubMed

Blank, Benoît; Glatz, Germund; Kempe, Rhett

2009-02-02

Two in one: The simultaneous formation of bimetallic mu-methylene bridged Rh(III) complexes as well as dimeric Rh(III) complexes with terminal chloromethyl groups is observed for P,N-ligand stabilized Rh(I) complexes by C-Cl bond activation of methylene chloride. A mechanistic proposal for the formation of both activation products is also discussed. The synthesis of Rh(I) complexes with P-functionalized aminopyridine ligands is reported as well as the first simultaneous observation of a single and double activation of C-Cl bonds of methylene chloride affording both a dimeric Rh(III) complex bearing terminal CH(2)Cl groups in addition to a binuclear Rh(III) complex with a bridging mu-CH(2) group. The structures of the oxidative addition products were obtained by X-ray diffraction studies and NMR experiments were performed to elucidate some aspects of the reaction pathway.

Bone generation in the reconstruction of a critical size calvarial defect in an experimental model.

PubMed

Por, Yong-Chen; Barceló, C Raul; Salyer, Kenneth E; Genecov, David G; Troxel, Karen; Gendler, El; Elsalanty, Mohammed E; Opperman, Lynne A

2008-03-01

This study was designed to investigate the optimal combination of known osteogenic biomaterials with shape conforming struts to achieve calvarial vault reconstruction, using a canine model. Eighteen adolescent beagles were divided equally into 6 groups. A critical-size defect of 6 x 2 cm traversed the sagittal suture. The biomaterials used for calvarial reconstruction were demineralized perforated bone matrix (DBM), recombinant human bone morphogenetic protein 2 (rhBMP2), and autogenous platelet-rich plasma (PRP). The struts used were cobalt chrome (metal) or resorbable plate. The groupings were as follows: 1) DBM + metal, 2) DBM + PRP + metal, 3) DBM + PRP + resorbable plate, 4) DBM + rhBMP2 + metal, 5) DBM + rhBMP2 + PRP + metal, and 6) DBM + rhBMP2 + resorbable plate. Animals were killed at 3 months after surgery. There was no mortality or major complications. Analysis was performed macroscopically and histologically and with computed tomography. There was complete bony regeneration in the rhBMP2 groups only. Non-rhBMP2 groups had minimal bony ingrowth from the defect edges and on the dural surface, a finding confirmed by computed tomographic scan and histology. Platelet-rich plasma did not enhance bone regeneration. Shape conformation was good with both metal and resorbable plate. rhBMP2, but not PRP, accelerated calvarial regeneration in 3 months. The DBMs in the rhBMP2 groups were substituted by new trabecular bone. Shape molding was good with both metal and resorbable plate.

Amphioxus: beginning of vertebrate and end of invertebrate type GnRH receptor lineage.

PubMed

Tello, Javier A; Sherwood, Nancy M

2009-06-01

In vertebrates, activation of the GnRH receptor is necessary to initiate the reproductive cascade. However, little is known about the characteristics of GnRH receptors before the vertebrates evolved. Recently genome sequencing was completed for amphioxus, Branchiostoma floridae. To understand the GnRH receptors (GnRHR) from this most basal chordate, which is also classified as an invertebrate, we cloned and characterized four GnRHR cDNAs encoded in the amphioxus genome. We found that incubation of GnRH1 (mammalian GnRH) and GnRH2 (chicken GnRH II) with COS7 cells heterologously expressing the amphioxus GnRHRs caused potent intracellular inositol phosphate turnover in two of the receptors. One of the two receptors displayed a clear preference for GnRH1 over GnRH2, a characteristic not previously seen outside the type I mammalian GnRHRs. Phylogenetic analysis grouped the four receptors into two paralogous pairs, with one pair grouping basally with the vertebrate GnRH receptors and the other grouping with the octopus GnRHR-like sequence and the related receptor for insect adipokinetic hormone. Pharmacological studies showed that octopus GnRH-like peptide and adipokinetic hormone induced potent inositol phosphate turnover in one of these other two amphioxus receptors. These data demonstrate the functional conservation of two distinct types of GnRH receptors at the base of chordates. We propose that one receptor type led to vertebrate GnRHRs, whereas the other type, related to the mollusk GnRHR-like receptor, was lost in the vertebrate lineage. This is the first report to suggest that distinct invertebrate and vertebrate GnRHRs are present simultaneously in a basal chordate, amphioxus.

[Reconstruction of maxillary sinus superior wall fractures with calcium phosphate cement/recombinant human bonemorphogenetic protein 7 compound implanted material in rabbit].

PubMed

Zhang, Qunhui; Yu, Feng; Zhang, Haoliang; Gong, Huicheng; Lin, Ying

2015-11-01

To evaluate the osteogenetic character and repairing maxillary sinus superior wall fractures capability of calcium phosphate cement (CPC) before and after combined with recombinant human bone morphogenetie protein-7(rhBMP-7). A 10 mmX5 mm bone defect in the maxillary sinus superior wall was induced by surgery in all 24 New Zealand white rabbits. These 24 rabbits were randomly divided into two groups. The defects were repaired with CPC group (n = 12) and CPC/rhBMP-7 group (n = 12). The osteogenesis of bone defect was monitored by gro'ss observation, histological examination, observation under scanning electron microscope and measurement of ALP activity at 6 and 12 weeks after the implantation. In group CPC,new bone was found to form slowly and little by little. In group CPC/rhBMP-7, however, new bone was observed to form early and massively. The ALP activity in group CPC showed significant statistical difference with that of group CPC/rhBMP-7 (P < 0.05). The CPC/rhBMP-7 composite has osteoconductibility and osteoinductibility, comparing the use of CPC/rhBMP-7 with CPC for the repair of orbital fracture, the former show obvious advantage repairing ability in maxillary sinus superior wall defect.

Rhnull syndrome: identification of a novel mutation in RHce.

PubMed

Rosa, K A; Reid, M E; Lomas-Francis, C; Powell, V I; Costa, F F; Stinghen, S T; Watanabe, A M; Carboni, E K; Baldon, J P; Jucksch, M M F; Castilho, L

2005-11-01

The deficiency of Rh proteins on red blood cells (RBCs) from individuals of the Rh(null) amorph type are the result of homozygosity for a silent RHCE in cis with a deleted RHD. A novel mutation in RHce was identified in two Caucasian Brazilian girls with the amorph type of Rh(null) who were born to parents who were first cousins. RBCs from the Rh(null) sisters and from family members were analyzed by serology and flow cytometry with specific antibodies. Genomic DNA and transcripts were tested by polymerase chain reaction and sequence analysis. Rh(null) RBCs were nonreactive with anti-Rh and anti-LW. Molecular analyses showed a deletion of RHD and of one nucleotide (960/963; GGGG-->GGG) in exon 7 of the RHce. This deletion introduced a frameshift after Gly321, a new C-terminal sequence, and a premature stop codon, resulting in a shorter predicted protein with 357 amino acids. The detection of a unique RHce transcript indicated that the two sisters were homozygous, whereas the other family members were heterozygous for the mutation. A novel mutation resulting in the amorph Rh(null) with loss of Rh antigen expression is described.

Effects of an exopolysaccharide (kefiran) on lipids, blood pressure, blood glucose, and constipation.

PubMed

Maeda, Hiroaki; Zhu, Xia; Omura, Kazunobu; Suzuki, Shiho; Kitamura, Shinichi

2004-01-01

Lactobacillus kefiranofaciens was reported to produce an exopolysaccharide named kefiran. In the present study, we developed a new medium, rice hydrolyzate (RH) medium, for the culture of L. kefiranofaciens. Structural analyses revealed that the exopolysaccharide produced by L. kefiranofaciens from RH medium was composed of a hexasaccharide repeating unit, and essentially identical to the kefiran reported in previous studies. A study on the effects of kefiran in animals demonstrated that kefiran significantly suppressed increase of blood pressure and reduced the serum cholesterol levels in SHRSP/Hos rats when subjects consumed excessive dietary cholesterol. Kefiran supplementation demonstrated the ability to significantly lower blood glucose in KKAy mice. In addition, the administration of kefiran in constipated SD rats caused an obvious improvement in the levels of fecal moisture and wet weights of feces. These results suggest that kefiran could be used as a functional food to prevent some commonly occurring diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mittal, Bharat B., E-mail: bmittal@nmh.org; Wang, Edward; Sejpal, Samir

Purpose: The current study examined the effect of recombinant human deoxyribonuclease (rhDNase) on quality of life (QOL) measures, clinical improvement, and DNA content of thick oropharyngeal secretions (OPS) in patients with head-and-neck (H and N) cancers. Methods and Materials: Thirty-six patients with local-regional advanced H and N cancer receiving chemoradiationtherapy (CRT) were randomized to receive either placebo or rhDNase. Endpoints included MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) and Functional Assessment of Cancer Therapy–Head and Neck (FACT-NH) scores, along with clinical assessment and DNA concentration of OPS. Results: There were no statistically significant differences in patients' QOL outcomes over themore » study period. Both groups showed an increase in symptom and interference scores, although patients in the rhDNase group showed a greater decline in both scores during the 3 months posttreatment. Similarly, both groups showed a decline in physical and functional well being but recovered in the 3 months posttreatment follow-up, with the rhDNase group exhibiting speedier recovery. Patients in the rhDNase group exhibited significant clinical improvement in OPS, blindly assessed by a physician, compared with the placebo group (67% vs 27%, respectively; P=.046). The rhDNase group showed no change in OPS-DNA concentration, although the placebo group showed a significant increase in DNA concentration during the drug trial (P=.045). There was no differences in acute toxicities between the 2 groups. Conclusions: Our preliminary data suggest that rhDNase did not significantly improve study primary endpoints of QOL measures compared with the placebo group. However, there was a significant improvement in secondary endpoints of clinically assessed OPS and DNA concentration compared with placebo in H and N cancer patients treated with CRT. Further investigation in larger numbers of patients is warranted.« less

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats.

PubMed

van Hoek, Ingrid M; Peremans, Kathelijne; Vandermeulen, Eva; Duchateau, Luc; Gommeren, Kris; Daminet, Sylvie

2009-04-01

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT(4)) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 microg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT(4) measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT(4) concentration, T/S uptake ratio before and 6h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 microg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.

Platinum-group elements fractionation by selective complexing, the Os, Ir, Ru, Rh-arsenide-sulfide systems above 1020 °C

NASA Astrophysics Data System (ADS)

Helmy, Hassan M.; Bragagni, Alessandro

2017-11-01

The platinum-group element (PGE) contents in magmatic ores and rocks are normally in the low μg/g (even in the ng/g) level, yet they form discrete platinum-group mineral (PGM) phases. IPGE (Os, Ir, Ru) + Rh form alloys, sulfides, and sulfarsenides while Pt and Pd form arsenides, tellurides, bismuthoids and antimonides. We experimentally investigate the behavior of Os, Ru, Ir and Rh in As-bearing sulfide system between 1300 and 1020 °C and show that the prominent mineralogical difference between IPGE (+Rh) and Pt and Pd reflects different chemical preference in the sulfide melt. At temperatures above 1200 °C, Os shows a tendency to form alloys. Ruthenium forms a sulfide (laurite RuS2) while Ir and Rh form sulfarsenides (irarsite IrAsS and hollingworthite RhAsS, respectively). The chemical preference of PGE is selective: IPGE + Rh form metal-metal, metal-S and metal-AsS complexes while Pt and Pd form semimetal complexes. Selective complexing followed by mechanical separation of IPGE (and Rh)-ligand from Pt- and Pd-ligand associations lead to PGE fractionation.

[Spermatogenesis of pulsatile gonadotropin-releasing hormone infusion versus gonadotropin therapy in male idiopathic hypogonadotropic hypogonadism].

PubMed

Huang, Bingkun; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Liu, Zhaoxiang; Nie, Min; Wu, Xueyan

2015-05-26

To compare the efficacies of pulsatile gonadotropin-releasing hormone (GnRH) versus human chorionic gonadotropin/human menopausal gonadotropin (HCG/HMG) for spermatogenesis in male idiopathic hypogonadotropic hypogonadism (IHH). For this retrospective study, a total of 92 male IHH outpatients from May 2010 to October 2014 were recruited and categorized into GnRH (n = 40) and HCG/HMG (n = 52) groups. Each subject selected one specific therapy voluntarily. The gonadotropin levels were measured in the first week and monthly post-treatment in GnRH group. And serum total testosterone (TT), testicular volume (TV) and rate of spermatogenesis were observed monthly post-treatment in two groups. Spermatogenesis, TT and TV were compared between two groups. All IHH patients were treated for over 3 months. The median follow-up periods in GnRH and HCG/HMG groups was 8.2 (3.0-18.4) and 9.2 (3.0-18.6) months respectively (P = 0.413). In GnRH group, LH ((0.5 ± 0.6) vs (3.4 ± 2.4) U/L, P < 0.01) and FSH ((1.3 ± 1.1) vs (5.8 ± 3.8) U/L, P < 0.01) increased after 1-week treatment. In GnRH group, at the end of follow-up, TT ((1.0 ± 1.0) vs (7.4 ± 5.2) nmol/L, P < 0.01) and TV ((2.3 ± 1.5) vs (8.1 ± 4.0) ml, P < 0.01) significantly increased compared to baseline. In HCG/HMG group, TT ((0.8 ± 0.6) vs (14.4 ± 8.0) nmol/L, P < 0.01) and TV ((2.3 ± 2.1) vs (7.6 ± 4.2) ml, P < 0.01) significantly increased after therapy. The success rate of spermatogenesis was 50.0% (20/40) in GnRH group versus 28.8% (15/52) in HCG/HMG group (P = 0.038). GnRH group required a shorter treatment time for initial sperm appearance than HCG/HMG group ((6.5 ± 3.1) vs (10.8 ± 3.7) months, P = 0.001). Pulsatile GnRH requires a shorter time for initiation of spermatogenesis than gonadotropin therapy in IHH male patients.

An ABO blood grouping discrepancy: Probable B(A) phenotype.

PubMed

Jain, Ashish; Gupta, Anubhav; Malhotra, Sheetal; Marwaha, Neelam; Sharma, Ratti Ram

2017-06-01

In B(A) phenotype, an autosomal dominant phenotype, there is a weak A expression on group B RBCs. We herein report a case of a probable B(A) phenotype in a first time 20-year old male donor. The cell and serum grouping were done using tube technique and also with blood grouping gel card (Diaclone, ABD cards for donors, BioRad, Switzerland). The antisera used were commercial monoclonal IgM type. To check for the weak subgroup of A, cold adsorption and heat elution was performed. The cell grouping was A weak B RhD positive while the serum grouping was B. There was no agglutination with O cells and the autologous control was also negative. It was a group II ABO discrepancy with or without group IV discrepancy. Results for both the eluate and last wash were negative. Hence, the possibility of weak subgroup of A was unlikely. Blood grouping gel card also showed a negative reaction in the anti-A column. One lot of anti-A was showing 'weak +' agglutination while the other lot was showing 'negative' reaction with the donor RBCs by tube technique. There was no agglutination observed with anti-A1 lectin. Our case highlights the serological characteristics of a B(A) phenotype. This case emphasizes the vital role of cell and serum grouping in detecting such discrepancies especially in donors which can lead to mislabeling of the blood unit and may be a potential risk for the transfusion recipient if not resolved appropriately. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nebulized hypertonic saline and recombinant human DNase in the treatment of pulmonary atelectasis in newborns.

PubMed

Dilmen, Ugur; Karagol, Belma Saygili; Oguz, Serife Suna

2011-06-01

The aim of this study was to compare and evaluate the efficacy of nebulized 3% hypertonic saline (HS) and recombinant human DNase (rhDNase) treatment for resolution of persistent atelectasis in newborns. Forty newborns (38 preterms) who did not respond to conventional treatment were enrolled to receive either nebulized 3% HS solution (n = 20) or rhDNase (n = 20) between September 2007 and March 2008. Clinical parameters, oxygen saturation and radiological response (chest X-ray scoring) were analyzed before and after administration of 3% HS or rhDNase. The patients of the nebulized 3% HS solution group improved better chest X-ray scores parameters than the patients of the rhDNase group: chest X-ray scores were 5.1 ± 1.9 vs 4.8 ± 1.7 before treatment and 1.0 ± 0.8 vs 2.1 ± 1.4 after treatment (P < 0.001). Resolution time of atelectasis did not differ between the two groups after whole treatment but the percentage of atelectasis resolution after 3 days treatment were 90% (18/20) in the 3% HS group and 70% (14/20) in the rhDNase group. The patients in the 3% HS group improved better also in clinical parameters in comparison to the rhDNase treatment. The difference of oxygen saturation before and after the treatment was 4.6 ± 0.8 in 3% HS group in comparison to 2.6 ± 0.1 in the rhDNase group (P < 0.05). All serum sodium levels were normal in two groups before and after the treatment modalities. This is the first study on the usefulness of nebulized 3% hypertonic saline solution in treating newborns with pulmonary atelectasis. In addition, 3% HS solution was a more effective therapeutic option on the basis of clinical and radiological improvement compared to rhDNase treatment in newborns with pulmonary atelectasis. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Microdose flare-up vs. flexible-multidose GnRH antagonist protocols for poor responder patients who underwent ICSI.

PubMed

Esinler, I

2014-01-01

To compare the performance of microdose flare-up (MF) and flexible-multidose gonadotropin-releasing hormone (GnRH) antagonist protocols in poor responder patients who underwent intracytoplasmic sperm injection (ICSI). One hundred and 12 consecutive patients (217 cycles) suspected to have poor ovarian response were enrolled. Group 1 (MF GnRH agonist group) constituted 64 patients (135 cycles) who underwent MF GnRH agonist protocol. Group 2 (flexible-multidose GnRH antagonist group) constituted 48 patients (82 cycles) who underwent flexible-multidose GnRH antagonist protocol. The duration of stimulation (d) (11.5 +/- 2.1 vs. 10.4 +/- 2.7, p < 0.01) and the total dose of gonadotropin used (IU) (5,892.9 +/- 1,725.7 vs. 4,367.5 +/- 1,582.1, p < 0.05) were significantly lower in Group 2 when compared to Group 1. The numbers of retrieved oocyte-cumulus complexes (4.5 +/- 3.6 vs. 5.9 +/- 4.9, p < 0.05), metaphase II oocytes (3.6 +/- 3.1 vs. 4.9 +/- 4.2, p < 0.05), two pronucleated oocytes (2.6 +/- 2.3 vs. 4.0 +/- 3.4, p < 0.05), the number of available embryos at day 3 (2.6 +/- 2.2 vs. 4.2 +/- 3.2, p < 0.05) and the rate of embryos with > or = seven blastomeres and < 10% fragmentation at day 3 (35.9% vs. 65.1%, p < 0.05) were significantly lower in Group 1 when compared to Group 2. The number of embryos transferred (2.2 +/- 1.3 vs. 2.4 +/- 0.9), the clinical pregnancy per embryo transfer (16.3% vs. 25.8%), and the implantation rate (8.6% vs. 12.2%) were comparable between groups. Although the flexible-multidose GnRH antagonist protocol produced better oocyte and embryo parameters, the clinical pregnancy rate and the implantation rates were comparable between the flexible-multidose GnRH antagonist and MF protocols in poor responder patients.

Non-antibiotic agent ginsenoside 20(S)-Rh2 enhanced the antibacterial effects of ciprofloxacin in vitro and in vivo as a potential NorA inhibitor.

PubMed

Zhang, Jingwei; Sun, Yuan; Wang, Yaoyao; Lu, Meng; He, Jichao; Liu, Jiali; Chen, Qianying; Zhang, Xiaoxuan; Zhou, Fang; Wang, Guangji; Sun, Xianqiang

2014-10-05

The aim of this study is to explore the potential enhancing effect of ginsenoside 20(S)-Rh2 (Rh2) towards ciprofloxacin (CIP) against Staphylococcus aureus (S. aureus) infection in vitro and in vivo, and analyze the possible mechanisms through NorA inhibition from a target cellular pharmacokinetic view. In combination with non-toxic dosage of Rh2, the susceptibilities of S. aureus strains to CIP were significantly augmented, and the antibacterial kinetics of CIP in the S. aureus strains were markedly promoted. This enhancing effect of Rh2 towards CIP was also observed in S. aureus infected peritonitis mice, with elevated survival rate and reduced bacteria counts in blood. However, Rh2 did not influence the plasma concentrations of CIP. Further analysis indicated that Rh2 significantly promoted the accumulations of CIP in S. aureus, and inhibited the NorA mediated efflux of pyronin Y. The expressions of NorA gene on S. aureus were positively correlated with the enhancing effect of Rh2 with CIP. This is the first report of the enhancing effect of Rh2 with CIP for S. aureus infection in vitro and in vivo, of which it is probably that Rh2 inhibited NorA-mediated efflux and promoted the accumulation of CIP in the bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of gonadoliberin analogue triptorelin on the pituitary-testicular complex in neonatal rats.

PubMed

Dygalo, N N; Shemenkova, T V; Kalinina, T S; Shishkina, G T

2014-02-01

Triptorelin, a synthetic analogue of neurohormone gonadoliberin (gonadotropin-releasing hormone, GnRH) administered daily to rats on postnatal days 5-7 suppressed the expression of GnRH receptor in the pituitary gland, but did not change functioning of the pituitary-testicular complex. Administration of triptorelin on postnatal days 12-14 (i.e. during the formation of pulsatile pattern of GnRH secretion and increasing levels of its mRNA receptor in the pituitary gland) had no effect on receptor expression, but increased the levels of luteinizing hormone mRNA in the pituitary gland and the weight of testes. At that time, blood levels of testosterone were lowered, which indicated disturbed pulsatile pattern of GnRH secretion.

Repeated hematopoietic stem and progenitor cell mobilization without depletion of the bone marrow stem and progenitor cell pool in mice after repeated administration of recombinant murine G-CSF.

PubMed

de Kruijf, Evert-Jan F M; van Pel, Melissa; Hagoort, Henny; Kruysdijk, Donnée; Molineux, Graham; Willemze, Roel; Fibbe, Willem E

2007-05-01

Administration of recombinant-human G-CSF (rhG-CSF) is highly efficient in mobilizing hematopoietic stem and progenitor cells (HSC/HPC) from the bone marrow (BM) toward the peripheral blood. This study was designed to investigate whether repeated G-CSF-induced HSC/HPC mobilization in mice could lead to a depletion of the bone marrow HSC/HPC pool with subsequent loss of mobilizing capacity. To test this hypothesis Balb/c mice were treated with a maximum of 12 repeated 5-day cycles of either 10 microg rhG-CSF/day or 0.25 microg rmG-CSF/day. Repeated administration of rhG-CSF lead to strong inhibition of HSC/HPC mobilization toward the peripheral blood and spleen after >4 cycles because of the induction of anti-rhG-CSF antibodies. In contrast, after repeated administration of rmG-CSF, HSC/HPC mobilizing capacity remained intact for up to 12 cycles. The number of CFU-GM per femur did not significantly change for up to 12 cycles. We conclude that repeated administration of G-CSF does not lead to depletion of the bone marrow HSC/HPC pool.

Can postoperative GnRH agonist treatment prevent endometriosis recurrence? A meta-analysis.

PubMed

Zheng, Qiaomei; Mao, Hongluan; Xu, Ying; Zhao, Jing; Wei, Xuan; Liu, Peishu

2016-07-01

To investigate whether postoperative GnRH agonist (GnRH-a) treatment can prevent endometriosis recurrence. This meta-analysis searched PubMed, Embase and Cochrane Library for relevant studies published online before June 2015. Seven randomized controlled trials including 328 patients with postoperative GnRH-a treatment and 394 patients in control group were included in the meta-analysis. In the meta-analysis, the recurrence rate of GnRH-a group compared with control group was evaluated with odds ratio (OR) and its 95 % confidence interval (CI). Heterogeneity, small study effect and publication bias were, respectively, assessed using Higgins I (2), sensitivity analysis and funnel plot. Postoperative GnRH-a treatment for endometriosis (pooled OR = 0.71; 95 % CI 0.52-0.96) was superior to expectant or placebo treatment in prevention of the recurrence. The recurrence rate decreased significantly in patients who received 6 months GnRH-a treatment (pooled OR = 0.59, 95 % CI 0.38-0.90), whereas no significant difference of recurrence rate existed between patients with 3 months post-surgical GnRH-a therapy and the control group (pooled OR = 0.87, 95 % CI 0.56-1.34). No significant heterogeneity and small study effect were found in the meta-analysis. However, publication bias did existed in the present meta-analysis. Longer-term (6 months) postoperative administration of GnRH-a can decrease the recurrence risk of endometriosis, whereas 3 months duration of GnRH-a therapy makes no significant difference in preventing the recurrence of endometriosis. Therefore, instead of a 3 month therapy, the duration of the postoperative administration should be longer enough (6 months) to prevent the recurrence of endometriosis.

Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

PubMed Central

Boos, Anja M; Weigand, Annika; Deschler, Gloria; Gerber, Thomas; Arkudas, Andreas; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

2014-01-01

New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation. PMID:25429218

Water in polymer membranes. 4. Raman scattering from cellulose acetate films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scherer, J.R.; Bailey, G.F.; Kint, S.

Raman scattering was observed from thin film optical waveguides of cellulose acetate exposed to water vapor from 0% to 100% relative humidity (RH), and from dilute solutions of water in methyl acetate. Spectra of cellulose acetate (CA398, 39.8% acetyl) at low RH and cellulose triacetate (CTA) at low and high RH are consistent with the presence of water monomers that are weakly hydrogen bonded to acetyl C=O groups. Differences between the spectra of water in CA398 and CTA at low RH are attributed to sequential hydrogen bonding involving OH groups in CA398. At high RH, CA398 and CTA (to amore » lesser extent) show bands attributed to water/water interactions that are similar to those found in sequentially hydrogen-bonded hydrates. CA398 films that are annealed at high temperatures exhibit decreased water/water interactions at high RH. Exposure of CA398 films to D/sub 2/O converts > 90% of all polymer OH groups to OD groups. This indicates that water is accessible to nearly all regions of the polymer containing OH groups. Annealing does not alter this accessibility but does reduce the total water content by roughly half, at 100% RH. Hydrogen-bonded C=O groups are associated with a band centered at 1731 cm/sup -1/ which increases in intensity with increasing water content in the film but does not shift in frequency. 38 references, 16 figures, 1 table.« less

A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.

PubMed

Pilli, Tania; Brianzoni, Ernesto; Capoccetti, Francesca; Castagna, Maria Grazia; Fattori, Sara; Poggiu, Angela; Rossi, Gloria; Ferretti, Francesca; Guarino, Elisa; Burroni, Luca; Vattimo, Angelo; Cipri, Claudia; Pacini, Furio

2007-09-01

Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine ((131)I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq (131)I had a similar successful rate to 3700 MBq in patients prepared with rhTSH. A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) (131)I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; (131)I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6-8 months later. Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases. Therapeutic (131)I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases.

Recombinant human brain natriuretic peptide ameliorates trauma-induced acute lung injury via inhibiting JAK/STAT signaling pathway in rats.

PubMed

Song, Zhi; Zhao, Xiu; Gao, Yan; Liu, Martin; Hou, Mingxiao; Jin, Hongxu; Cui, Yan

2015-05-01

JAK/STAT signal pathway plays an important role in the inflammation process of acute lung injury (ALI). This study aimed to investigate the correlation between recombinant human brain natriuretic peptide (rhBNP) and the JAK/STAT signaling pathway and to explore the protective mechanism of rhBNP against trauma-induced ALI. The arterial partial pressure in oxygen, lung wet-dry weight ratios, protein content in bronchoalveolar lavage fluid, the histopathologic of the lung, as well as the protein expressions of STAT1, JAK2, and STAT3 were detected. Sprague-Dawley rats were randomly divided into five groups: a control group, a sham-operated group, an ALI group, an ALI + rhBNP group, and an ALI + AG490 group. At 4 hours, 12 hours, 1 day, 3 days, and 7 days after injury, injured lung specimens were harvested. rhBNP pretreatment significantly ameliorated hypoxemia and histopathologic changes and alleviated pulmonary edema in trauma-induced ALI rats. rhBNP pretreatment reduced the phosphorylated protein and total protein level of STAT1. Similarly to JAK-specific inhibitor AG490, rhBNP was shown to significantly inhibit the phosphorylation of JAK2 and STAT3 in rats with trauma-induced ALI. Our experimental findings indicated that rhBNP can protect rats against trauma-induced ALI and that its underlying mechanism may be related to the inhibition of JAK/STAT signaling pathway activation.

Misdiagnosis of resistant hypertension: Real frequency of true resistant hypertension in patients with suspected resistance to treatment.

PubMed

Doménech, Mónica; Sastre, Enric; Camafort, Miguel; Sierra, Cristina; Coca, Antonio

2018-01-12

Resistant hypertension(RH) has been defined as failure to control office blood pressure (BP) despite the use of≥3 different antihypertensive agents at optimal doses, including, ideally, a diuretic. Apparent RH, defines patients with an incorrect diagnosis of RH due to different causes. The objective was to determine whether most patients with RH in fact have apparent but not true RH. Observational study involving 93 patients with suspected RH, being 60 patients finally included. Screening for secondary causes of hypertension was perfomed. True RH was defined as office BP>140/90mmHg despite full doses of 3 antihypertensive drugs including a diuretic. Mean age 63.7±9.8years, 68.3%were male. Office BP 154.3±14.4/84.4±13.7mmHg. Of the 60 patients, 23.3% had white coat effect, 3.3% didn't have a diuretic and 8.3% were non-adherent-to-treatment. Accordingly, 58.3% were classified as true RH. Spironolactone was added in 62.5% of patients of whom 78.4% achieved ambulatory BP control. Almost half of the patients with suspected RH were not really true RH. We provide more evidence of excess of fluid retention as an underlying cause of lack of BP control in patients with RH, reinforce the relevant paper of spironolactone for the management in those patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

PubMed

Toyama, K; Yaguchi, M; Mizoguchi, H; Masuda, M; Urabe, A; Ikeda, Y; Aoki, I; Shinbo, T; Togawa, A; Hirashima, K; Miura, Y; Hirose, S; Tsuruoka, N; Omine, M; Kamakura, M; Saito, T; Arimori, S; Aoki, N; Kuraishi, Y; Hirai, H; Asano, S; Mori, M; Shirai, T; Muto, Y; Takaku, F

1996-12-01

The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study.

PubMed

Taïeb, D; Sebag, F; Cherenko, M; Baumstarck-Barrau, K; Fortanier, C; Farman-Ara, B; De Micco, C; Vaillant, J; Thomas, S; Conte-Devolx, B; Loundou, A; Auquier, P; Henry, J F; Mundler, O

2009-07-01

Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. The aims of the present prospective randomized study were to evaluate the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of both procedures. L-T4 was initiated in both groups after thyroidectomy. After randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The functional assessment of chronic illness therapy-fatigue (FACIT-F) was administered from the early postoperative period to 9 months. Socio-demographic parameters, anxiety and depression scales were also evaluated (CES-D, BDI and Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck ultrasonography. A total of 74 patients were enrolled for the study. There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in the hypothyroid group with significant differences in FACIT-F TOI (P < 10(-3)), FACT-G total score (P = 0.005) and FACIT-F total score (P = 0.003). By contrast, QoL was preserved in the rhTSH group. In the multivariate analysis, FACIT-TOI changes were only affected by the modality of TSH stimulation performed for RRA. From 3 to 9 months, changes of QoL scales and subscales were no longer statistically different in both groups of patients. Based on serum rhTSH-stimulated Tg alone (Tg < 0.8 microg/l, BRAHMS Tg Kryptor), no difference in ablation success was observed between rhTSH and hypothyroidism groups, 91.7% and 97.1%, respectively. A higher rate of persistent thyroid remnants was observed in the rhTSH arm, although in most cases uptake was < 0.1% and of no clinical significance. rhTSH preserves QoL of patients undergoing RRA with similar rates of ablation success compared to hypothyrodism. However, there is a wide heterogeneity in the clinical impact of hypothyroidism.

Perioperative anaesthetic management of penetrating neck injury associated with Rh blood type in a young adult

PubMed Central

Wang, Tao; Zhou, Yeting; Shi, Jiaohui; Wang, Zhichun

2013-01-01

We describe here a young adult patient with penetrating neck injuries (PNI) with an Rh negative blood type and discuss the perioperative anaesthetic management of single-stage surgical exploration under general anaesthesia and extracorporeal circulation in this patient. The patient had zone II PNI and he was in a haemodynamically progressive unstable state, and the knife penetrated the left internal jugular vein, superior thyroid artery and recurrent laryngeal nerve; the trachea and the oesophagus were swelling at a rapid rate. Eight weeks after operation, the patient was discharged from the hospital without any complications. PMID:23429024

Allogeneic Peripheral Blood Stem Cell Collection as of 2008

PubMed Central

Rhodes, Beverly; Anderlini, Paolo

2015-01-01

The rapid growth of the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize and collect allogeneic peripheral blood stem cells (PBSCs) for transplantation has made it a new international standard. While the procedure remains safe, older donors, donors with significant comorbidities and pediatric donors are now often employed. This brings a new set of challenges in the donor evaluation, medical clearance, informed consent and collection process. Rare and unexpected severe adverse events related to rhG-CSF administration and PBSC apheresis have been described. Proper PBSC donor counseling, evaluation and care have become even more important. PMID:18501676

Utilization of anti-RhD in the emergency department after blunt trauma.

PubMed

Thorp, John M

2008-02-01

In the United States, trauma occurs in 6% to 7% of pregnancies. Its severity may range from critical injuries where the mother's life is at risk, to apparently minor injuries, which might not be associated with any worrisome symptoms. One of the risks associated with a traumatic event is fetomaternal hemorrhage--the transfer of fetal blood cells into the maternal circulation. If the maternal blood type is rhesus negative and the fetus is rhesus positive, even a small amount of blood can cause the mother to develop antibodies against the fetal Rho D antigen, thus becoming sensitized. In subsequent pregnancies, this can lead to hemolytic disease of the fetus or newborn, which, if severe, is associated with total body edema, hepatosplenomegaly and heart failure, and intrauterine death. Although there are no published studies specific to the US population, poor awareness of the risk of sensitization following trauma and underutilization of anti-RhD in the emergency department has been reported in countries such as Canada and the United Kingdom. This article reminds caregivers of the risk of rhesus sensitization following blunt trauma, in order that they can administer anti-RhD appropriately and hemolytic disease of the fetus or newborn can be prevented.

Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection-embryo transfer cycle.

PubMed

Kahraman, Korhan; Berker, Bulent; Atabekoglu, Cem Somer; Sonmezer, Murat; Cetinkaya, Esra; Aytac, Rusen; Satiroglu, Hakan

2009-06-01

To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. Prospective, randomized, clinical study. University hospital. Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.

Physiological and subjective responses to low relative humidity in young and elderly men.

PubMed

Sunwoo, Yujin; Chou, Chinmei; Takeshita, Junko; Murakami, Motoko; Tochihara, Yutaka

2006-05-01

In order to compare the physiological and the subjective responses to low relative humidity of elderly and young men, we measured saccharin clearance time (SCT), frequency of blinking, hydration state of the skin, transepidermal water loss (TEWL), sebum level recovery and skin temperatures as physiological responses. We asked subjects to evaluate thermal, dryness and comfort sensations as subjective responses using a rating scale. Eight non-smoking healthy male students (21.7+/-0.8 yr) and eight non-smoking healthy elderly men (71.1+/-4.1 yr) were selected. The pre-room conditions were maintained at an air temperature (Ta) of 25 degrees C and a relative humidity (RH) of 50%. The test-room conditions were adjusted to provide 25 degrees C Ta and RH levels of 10%, 30% and 50%. RH had no effect on the activity of the sebaceous gland or change of mean skin temperature. SCT of the elderly group under 10% RH was significantly longer than that of the young group. In particular, considering the SCT change, the nasal mucous membrane seems to be affected more in the elderly than in the young in low RH. Under 30% RH, the eyes and skin become dry, and under 10% RH the nasal mucous membrane becomes dry as well as the eyes and skin. These findings suggested that to avoid dryness of the eyes and skin, it is necessary to maintain greater than 30% RH, and to avoid dryness of the nasal mucous membrane, it is necessary to maintain greater than 10% RH. On the thermal sensation of the legs, at the lower humidity level, the elderly group felt cooler than the young group. On the dry sensation of the eyes and throat, the young group felt drier than the elderly group at the lower humidity levels. From the above results, the elderly group had difficulty in feeling dryness in the nasal mucous membrane despite being easily affected by low humidity. On the other hand, the young group felt the change of humidity sensitively despite not being severely affected by low humidity. Ocular mucosa and physiology of skin by dryness showed no difference by age. In the effect of longer exposure (180 min.) to low RH, only TEWL showed a slight decrease after 120 minutes in 30% RH, and all the measured results showed no noticeable differences compared with the result at 120 minutes.

A Randomized Clinical Trial Evaluating rh-FGF-2/β-TCP in Periodontal Defects.

PubMed

Cochran, D L; Oh, T-J; Mills, M P; Clem, D S; McClain, P K; Schallhorn, R A; McGuire, M K; Scheyer, E T; Giannobile, W V; Reddy, M S; Abou-Arraj, R V; Vassilopoulos, P J; Genco, R J; Geurs, N C; Takemura, A

2016-05-01

Biological mediators have been used to enhance periodontal regeneration. The aim of this prospective randomized controlled study was to evaluate the safety and effectiveness of 3 doses of fibroblast growth factor 2 (FGF-2) when combined with a β-tricalcium phosphate (β-TCP) scaffold carrier placed in vertical infrabony periodontal defects in adult patients. In this double-blinded, dose-verification, externally monitored clinical study, 88 patients who required surgical intervention to treat a qualifying infrabony periodontal defect were randomized to 1 of 4 treatment groups-β-TCP alone (control) and 0.1% recombinant human FGF-2 (rh-FGF-2), 0.3% rh-FGF-2, and 0.4% rh-FGF-2 with β-TCP-following scaling and root planing of the tooth prior to a surgical appointment. Flap surgery was performed with EDTA conditioning of the root prior to device implantation. There were no statistically significant differences in patient demographics and baseline characteristics among the 4 treatment groups. When a composite outcome of gain in clinical attachment of 1.5 mm was used with a linear bone growth of 2.5 mm, a dose response pattern detected a plateau in the 0.3% and 0.4% rh-FGF-2/β-TCP groups with significant improvements over control and 0.1% rh-FGF-2/β-TCP groups. The success rate at 6 mo was 71% in the 2 higher-concentration groups, as compared with 45% in the control and lowest treatment groups. Percentage bone fill in the 2 higher-concentration groups was 75% and 71%, compared with 63% and 61% in the control and lowest treatment group. No increases in specific antibody to rh-FGF-2 were detected, and no serious adverse events related to the products were reported. The results from this multicenter trial demonstrated that the treatment of infrabony vertical periodontal defects can be enhanced with the addition of rh-FGF-2/β-TCP (ClinicalTrials.gov NCT01728844). © International & American Associations for Dental Research 2016.

Accurate quantitation of D+ fetomaternal hemorrhage by flow cytometry using a novel reagent to eliminate granulocytes from analysis.

PubMed

Kumpel, Belinda; Hazell, Matthew; Guest, Alan; Dixey, Jonathan; Mushens, Rosey; Bishop, Debbie; Wreford-Bush, Tim; Lee, Edmond

2014-05-01

Quantitation of fetomaternal hemorrhage (FMH) is performed to determine the dose of prophylactic anti-D (RhIG) required to prevent D immunization of D- women. Flow cytometry (FC) is the most accurate method. However, maternal white blood cells (WBCs) can give high background by binding anti-D nonspecifically, compromising accuracy. Maternal blood samples (69) were sent for FC quantitation of FMH after positive Kleihauer-Betke test (KBT) analysis and RhIG administration. Reagents used were BRAD-3-fluorescein isothiocyanate (FITC; anti-D), AEVZ5.3-FITC (anti-varicella zoster [anti-VZ], negative control), anti-fetal hemoglobin (HbF)-FITC, blended two-color reagents, BRAD-3-FITC/anti-CD45-phycoerythrin (PE; anti-D/L), and BRAD-3-FITC/anti-CD66b-PE (anti-D/G). PE-positive WBCs were eliminated from analysis by gating. Full blood counts were performed on maternal samples and female donors. Elevated numbers of neutrophils were present in 80% of patients. Red blood cell (RBC) indices varied widely in maternal blood. D+ FMH values obtained with anti-D/L, anti-D/G, and anti-HbF-FITC were very similar (r = 0.99, p < 0.001). Correlation between KBT and anti-HbF-FITC FMH results was low (r = 0.716). Inaccurate FMH quantitation using the current method (anti-D minus anti-VZ) occurred with 71% samples having less than 15 mL of D+ FMH (RBCs) and insufficient RhIG calculated for 9%. Using two-color reagents and anti-HbF-FITC, approximately 30% patients had elevated F cells, 26% had no fetal cells, 6% had D- FMH, 26% had 4 to 15 mL of D+ FMH, and 12% patients had more than 15 mL of D+ FMH (RBCs) requiring more than 300 μg of RhIG. Without accurate quantitation of D+ FMH by FC, some women would receive inappropriate or inadequate anti-D prophylaxis. The latter may be at risk of immunization leading to hemolytic disease of the newborn. © 2013 American Association of Blood Banks.

Differential testosterone response to GnRH-induced LH release before and after musth in adult Asian elephant (Elephas maximus) bulls.

PubMed

Somgird, Chaleamchat; Sripiboon, Supaphen; Mahasawangkul, Sittidet; Boonprasert, Khajohnpat; Brown, Janine L; Stout, Tom A E; Colenbrander, Ben; Thitaram, Chatchote

2016-04-15

Bull elephants exhibit marked increases in testosterone secretion during musth, and studies have shown a heightened sensitivity of the testis to GnRH-stimulated testosterone production in musth compared to nonmusth males. However, activity of the hypothalamo-pituitary-gonadal axis before or soon after musth has not been studied in detail. The aim of this study was to evaluate LH and testosterone responses to GnRH challenge in nine adult Asian elephant (Elephas maximus) bulls during three periods relative to musth: premusth, postmusth, and nonmusth. Bulls were administered 80 μg of a GnRH agonist, and blood was collected before and after injection to monitor serum hormone concentrations. The same bulls were injected with saline 2 weeks before each GnRH challenge and monitored using the same blood collection protocol. All bulls responded to GnRH, but not saline, with an increase in LH and testosterone during all three periods. The mean peak LH (1.76 ± 0.19 ng/mL; P < 0.001) and testosterone (6.71 ± 1.62 ng/mL; P = 0.019) concentrations after GnRH were higher than the respective baselines (0.57 ± 0.07 ng/mL, 3.05 ± 0.60 ng/mL). Although basal- and GnRH-induced LH secretion were similar across the stages, evaluation of the area under the curve in GnRH-treated bulls indicated that the testosterone response was greatest during premusth (2.84 ± 0.76 area units; P = 0.019) compared to postmusth (2.02 ± 0.63 area units), and nonmusth (2.01 ± 0.46 area units). This confirms earlier reports that GnRH stimulates LH release and subsequent testosterone production in bull elephants. Furthermore, although the hypothalamo-pituitary-gonadal axis is active throughout the year, the testis appears to be more responsive to LH in terms of testosterone production in the period leading up to musth, compared to the nonmusth and postmusth periods. This heightened sensitivity, perhaps as a result of LH receptor up-regulation, may prime the testis for maximal testosterone production, leading to the physiological and behavioral changes associated with musth. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of the osteogenesis and fusion rates between activin A/BMP-2 chimera (AB204) and rhBMP-2 in a beagle's posterolateral lumbar spine model.

PubMed

Zheng, Guang Bin; Yoon, Byung-Hak; Lee, Jae Hyup

2017-10-01

Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in a rodent model, but there is no report about the effectiveness of AB204 in a large animal model. The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in a beagle's posterolateral lumbar fusion model. This is a randomized control animal study. Seventeen male beagle dogs were included. Bilateral posterolateral fusion was performed at the L1-L2 and L4-L5 levels. Biphasic calcium phosphate (2 cc), rhBMP-2 (50 µg)+BCP (2 cc), or AB204 (50 µg)+BCP (2 cc) were implanted into the intertransverse space randomly. X-ray was performed at 4 and 8 weeks. After 8 weeks, the animals were sacrificed, and new bone formation and fusion rate were evaluated by manual palpation, computed tomography (CT), and undecalcified histology. The AB204 group showed significantly higher fusion rate (90%) than the rhBMP-2 group (15%) or the Osteon group (6.3%) by manual palpation. On x-ray and CT assessment, fusion rate and the volume of newly formed bone were also significantly higher in AB204 group than other groups. In contrast, more osteolysis was found in rhBMP-2 group (40%) than in AB204 group (10%) on CT study. In histologic results, new bone formation was sufficient between transverse processes in AB204 group, and obvious trabeculation and bone remodeling were observed. But in rhBMP-2 group, new bone formation was less than AB204 group and osteolysis was observed between the intertransverse spaces. A low dose of AB204 with BCP as a carrier significantly promotes the fusion rate in a large animal model when compared with the rhBMP-2. These findings demonstrate that AB204 could be an alternative to rhBMP-2 to improve fusion rate. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic changes in the hypothalamic-pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study.

PubMed

Wang, Limin; Wang, Qian; Li, Guimei; Liu, Wendong

2015-09-01

The objective of this study was to investigate changes in the hypothalamic-pituitary-adrenal (HPA) axis after recombinant human growth hormone (rhGH) therapy. Subjects included children with growth hormone deficiency (GHD). We conducted a multicenter, retrospective study that assessed 72 GHD patients treated with rhGH during 6 months. Patients were classified into two groups: isolated GHD (IGHD; n=20) and multiple pituitary hormone deficiencies (MPHD; n=52). The HPA axis and other hormones were evaluated at baseline and every 3 months. In the MPHD group, 32 patients had adrenocorticotrophic hormone deficiency and received hydrocortisone before rhGH therapy. In the other 20/52 MPHD patients, the cortisol (COR) level was significantly reduced after rhGH therapy. Moreover, 10 patients showed low COR levels. In the IGHD group, COR levels also decreased, but remained within the normal range. During rhGH therapy, COR levels were reduced, particularly in patients with MPHD. HPA axis should be monitored during rhGH therapy.

Blood bank issues associated with red cell exchanges in sickle cell disease.

PubMed

Sarode, Ravindra; Altuntas, Fevzi

2006-12-01

Sickle cell disease (SCD) patients are prone to develop complications that include stroke, acute chest syndrome, and other crises. Some of these complications require chronic transfusion therapy or red cell exchange (RCE), either for therapeutic or prophylactic reasons. Due to a discrepancy of red cell antigens between African Americans and Caucasians (majority blood donors), the incidence of alloantibody formation is very high, which makes it difficult to find compatible red cell units, especially for urgent RCE. Some of the above conditions require immediate oxygen delivery to the tissues. Thus, SCD patients undergoing RCE should receive red blood cells with special attributes that include matching for Rh and Kell blood group antigens; RBCs should be fresh in order to provide (1) immediate oxygen delivery and (2) longer surviving cells to reduce the interval between RCE. Also, these units should be pre-storage leukoreduced to prevent febrile non-hemolytic reactions and screened for sickle cell traits to avoid transfusing red cells containing HbS. This requires a concerted effort between the apheresis unit, the local blood bank, and the central blood supplier.

rhG-CSF in healthy donors: mobilization of peripheral hemopoietic progenitors and effect on peripheral blood leukocytes.

PubMed

Sica, S; Rutella, S; Di Mario, A; Salutari, P; Rumi, C; Ortu la Barbera, E; Etuk, B; Menichella, G; D'Onofrio, G; Leone, G

1996-08-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16 micrograms/kg/day was given to 9 healthy donors to recruit hemopoietic progenitors (HP) for allogeneic transplantation or donor leukocyte infusion. rhG-CSF was administered s.c. for 5 days. No side effects were encountered except for moderate bone pain and lumbago. Mobilization was effective, reaching a peak median value of 187 x 10(3) CD34+ cells/ml (range 51.2-1127) and 2170 x 10(3) colony-forming units-granulocyte macrophage (CFU-GM)/ml (range 1138-4190). Peak values were obtained at a median of 4 days of rhG-CSF and represented, respectively, a 13-fold and a 37-fold increase from baseline values (p = 0.0007 and p = 0.006). White blood cell (WBC) counts increased 6-fold from baseline values (p < 0.0007) and reached a median peak of 34 x 10(6)/ml (23.5-59). Polymorphonuclear (PMN), and mononuclear (MNC) cells increased 10-fold and 2-fold, respectively (p = 0.0039 and p = 0.0026) and reached a median peak of 32.1 x 10(6)/ml (18.2-52) and 4.42 x 10(6)/ml (3.14-12.42). Absolute lymphocyte and monocyte counts increased at peak day in all donors 1.5-fold and 5.7-fold from baseline values (p = 0.0017 and p = 0.0018). In 7 of 9 donors, lymphocyte subsets were analyzed in detail. CD3+ and CD19+ lymphocytes increased 1.5-fold and 3-fold, respectively (p = 0.032 for both). NK and activated T lymphocytes doubled at a median of 4 days of rhG-CSF (p = 0.032 and p = NS, respectively). Similar changes were observed in lymphocytes collected in leukapheresis product. T helper and T suppressor subsets displayed a similar increase. Thus, besides the anticipated priming effect on HP and PMN, rhG-CSF in healthy donors produced an unexpected and still unexplained modification of lymphocyte subsets in peripheral blood.

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers

PubMed Central

Anderlini, Paolo

2015-01-01

Purpose of Review Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed. Recent Findings In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. G-CSF receptors were identified in a variety of non-myeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for PBPCs, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare. Summary rhG-CSF effects in healthy volunteers, while normally transient and self-limiting, are now believed to be more complex and heterogeneous that previously thought. While rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals. PMID:19057203

Selective interactions among Rh, ABO, and sex ratio of newborns.

PubMed

Valenzuela, C Y; Walton, R

1985-01-01

The hypothesis that the Rh and ABO blood systems behave like the HLA system in relation to mother-conception tolerance-rejection mechanisms was tested in 25,501 mother-infant pairs. According to this hypothesis, heterozygotes carrying a paternal gene that is not present in their mothers should be better tolerated than homozygotes. Significantly more BO infants born to AO mothers. AO infants born to BO mothers, Rh(+) heterozygotes born to Rh(-) mothers, and less significantly AO infants born to OO mothers confirm the hypothesis. Fewer homozygotes occurred in Rh(-) infants born to Rh(+) mothers and in O infants born to non-O mothers. Deviations from the Hardy-Weinberg equilibrium found in the ABO system were modified by the Rh and sex of the infant. These data strongly support the hypothesis that at least two feto-maternal systems influence the destiny of pregnancies: the classical known incompatibility system which operates late in pregnancy and a new one which is based on the induction of maternal tolerance early in pregnancy: maternal tolerance seems to be better elicited by heterozygous eggs or embryos carrying a gene not present in the mother. The data also support the hypothesis that the sex ratio is influenced by feto-maternal tolerance-rejection mechanisms associated with the ABO and Rh systems.

Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies.

PubMed

Wright, Katherine E; Hjerrild, Kathryn A; Bartlett, Jonathan; Douglas, Alexander D; Jin, Jing; Brown, Rebecca E; Illingworth, Joseph J; Ashfield, Rebecca; Clemmensen, Stine B; de Jongh, Willem A; Draper, Simon J; Higgins, Matthew K

2014-11-20

Invasion of host erythrocytes is essential to the life cycle of Plasmodium parasites and development of the pathology of malaria. The stages of erythrocyte invasion, including initial contact, apical reorientation, junction formation, and active invagination, are directed by coordinated release of specialized apical organelles and their parasite protein contents. Among these proteins, and central to invasion by all species, are two parasite protein families, the reticulocyte-binding protein homologue (RH) and erythrocyte-binding like proteins, which mediate host-parasite interactions. RH5 from Plasmodium falciparum (PfRH5) is the only member of either family demonstrated to be necessary for erythrocyte invasion in all tested strains, through its interaction with the erythrocyte surface protein basigin (also known as CD147 and EMMPRIN). Antibodies targeting PfRH5 or basigin efficiently block parasite invasion in vitro, making PfRH5 an excellent vaccine candidate. Here we present crystal structures of PfRH5 in complex with basigin and two distinct inhibitory antibodies. PfRH5 adopts a novel fold in which two three-helical bundles come together in a kite-like architecture, presenting binding sites for basigin and inhibitory antibodies at one tip. This provides the first structural insight into erythrocyte binding by the Plasmodium RH protein family and identifies novel inhibitory epitopes to guide design of a new generation of vaccines against the blood-stage parasite.

Bone tissue engineering by way of allograft revitalization: mechanistic and mechanical investigations using a porcine model.

PubMed

Runyan, Christopher M; Ali, Samantha T; Chen, Wendy; Calder, Bennet W; Rumburg, Aaron E; Billmire, David A; Taylor, Jesse A

2014-05-01

"Allograft revitalization" is a process in which cadaveric bone is used to generate well-vascularized living bone. We had previously found that porcine allograft hemimandibles filled with autologous adipose-derived stem cells (ASCs) and recombinant human bone morphogenetic protein-2-soaked absorbable collagen sponge (rhBMP-2/ACS) were completely replaced by vascularized bone, provided the construct had been incubated within a periosteal envelope. The present study sought to deepen our understanding of allograft revitalization by investigating the individual contributions of ASCs and rhBMP-2 in the process and the mechanical properties of the revitalized allograft. Porcine allograft hemimandible constructs were implanted bilaterally into rib periosteal envelopes in 8 pigs. To examine the contributions of ASCs and rhBMP-2, the following groups were assessed: group 1, periosteum alone; group 2, periosteum+ASCs; group 3, periosteum+rhBMP-2/ACS; and group 4, periosteum+ASCs+rhBMP-2/ACS. After 8 weeks, the allograft constructs were harvested for micro-computed tomography (CT) and histologic analyses and 3-point bending to assess the strength. On harvesting, the constructs receiving rhBMP-2/ACS had significantly greater bone shown by micro-CT than those receiving periosteum only (51,463 vs. 34,310 mm3; P = .031). The constructs receiving ASCs had increased bone compared to group 1 (periosteum only), although not significantly (P = .087). The combination of rhBMP-2/ACS with ASCs produced bone (50,399 mm3) equivalent to that of the constructs containing rhBMP-2/ACS only. The 3-point bending tests showed no differences between the 4 groups and a nonimplanted allograft or native mandible (P = .586), suggesting the absence of decreased strength of the allograft bone when revitalized. These data have shown that rhBMP-2/ACS significantly stimulates new bone formation by way of allograft revitalization and that the revitalized allograft has equivalent mechanical strength to native bone. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

A uniform method for the simultaneous blood group phenotyping of Fya , Fyb , Jka , Jkb , S, s̅, P1, k applying lateral-flow technique.

PubMed

Caesar, A; Meyer, S; Trost, N; Neuenschwander, K; Geisen, C; Frey, B M; Gassner, C; Schwind, P

2018-02-01

A lateral flow assay for simultaneous blood group typing of ABO, RhD, C, E, c, e, Cw and K with stable end-point and without centrifugation is in routine use since several years (MDmulticard ® ). The typing of extended phenotype parameters belonging to the Duffy, Kidd, MNSs blood group systems and others, however, has not yet been demonstrated for this technique. Reliable detection of Fy x , a weak Fy b phenotype with a pronounced quantitative reduction of the number of Fy b antigens on the erythrocyte surface, remains a weakness of current serological blood grouping techniques. The performance characteristics of the following reagents were evaluated in donor and patient samples in lateral flow technology (MDmulticard ® ): Anti-Fy a , -Fy b , -Jk a , -Jk b , -S, -s̅, -P1 and -k. The sensitivity to detect Fy x was in addition evaluated with Fy x positive samples, which had been preselected by MALDI-TOF MS-based genotyping. All results obtained with the MDmulticard ® were in full accordance with those of the CE-certified reference products for all the eight reagent formulations used: Anti-Fy a , -Fy b , -Jk a , -Jk b , -S, -s̅, -P1 and -k. Also, all Fy x phenotypes of the selected population of 93 positive samples, originally identified by MALDI-TOF MS-based genotyping, were reliably detected by the lateral flow assay. Extended phenotype blood group parameters, including the serologically challenging Fy x phenotype, can be determined simultaneously, rapidly and accurately using the lateral flow (MDmulticard ® ) technology, even in cases when IgG class antibodies are the only source of diagnostic antibodies. © 2017 International Society of Blood Transfusion.

INRA, a new high-frequency antigen in the INDIAN (IN023) blood group system.

PubMed

Joshi, Sanmukh R; Sheladiya, Ankita; Mendapara-Dobariya, Kinjal V

2017-01-01

The INDIAN blood group system comprises 4 antigens sensitive to enzymes and 2-aminoethyl isothiouronium bromide (AET). The patient's antibody was investigated for its specificity to the high-frequency antigens (HFA) of this system. Low ionic strength solution (LISS)-tube/LISS-indirect antiglobulin test (IAT) methods were used. The patient's red blood cells (RBCs) were tested with antisera to HFA. Her antibody was tested with RBCs lacking the HFA. Furthermore, it was tested with RBCs as untreated or treated with enzyme or AET. The genetic sequence was studied for mutation in CD44 gene that encodes INDIAN antigens. The patient was grouped A1B, RhD+, antibody screening test positive, direct antiglobulin test negative. A negative autocontrol test had suggested to the alloantibody being present. Antibody had agglutinated RBCs in LISS-tube at RT and by LISS-IAT at 37°C. The RBCs of the 11-cell panel, those lacking HFA and from 50 random donors, were agglutinated by her antibody indicating its specificity to the HFA, though the RBCs of Lu (a-b-)/In (Lu) type showed a weaker reaction. The patient's RBCs were agglutinated by antisera to a number of the enzyme-sensitive HFA, including those of INDIAN blood groups. The antibody showed reduced reactivity with the RBCs treated with papain, chymotrypsin, and AET but resistant to trypsin and dithiothreitol. The patient's genetic sequence revealed a novel homozygous mutation 449G>A in exon 5 of CD44 . The antibody to enzyme sensitive HFA was tested for serological and molecular genetics studies and found to be directed to the novel HFA, named as INRA of the INDIAN blood group system and was assigned a numerical symbol IN: 005 by the International Society of Blood Transfusion (ISBT).

Usefulness of magnetic resonance findings of the hypothalamic-pituitary region in the management of short children with growth hormone deficiency: evidence from a longitudinal study.

PubMed

Kalina, Maria A; Kalina-Faska, Barbara; Gruszczyńska, Katarzyna; Baron, Jan; Małecka-Tendera, Ewa

2012-01-01

The purpose of this study is to assess the relationship between magnetic resonance images (MRI) of the hypothalamic-pituitary (H-P) region and response to recombinant human growth hormone (rhGH) treatment in short children with growth hormone deficiency, basing on changes of auxologic parameters, as well as to answer the question if MRI may serve for selecting and monitoring the rhGH responders. The study group comprised 85 children treated with rhGH, aged 7.3-18.7 years, followed for the mean period of 3.2 years (range, 2.1-9.5 years). Auxologic parameters (height deficit hSDS, deviation from the mid-parental height hSDS-mpSDS, bone delay index bone age/chronological age ratio (BA/CA)) were assessed before, during and at the end of rhGH treatment; growth velocity was calculated before and during rhGH therapy. Parameters were correlated with the MRI of the H-P region. Structural anomalies of the H-P region were found in 22 (25.9%) children: empty sella syndrome (ESS) in 12 (14.1%) patients, ectopic posterior pituitary (EPP) in ten (11.8%). Patients' height deficit and their deviation from parental height before rhGH therapy was significantly greater in the EPP group (median hSDS = -3.8; hSDS-mpSDS = -2.5), bone age delay was the greatest in the ESS group (median BA/CA = 0.69), after therapy - in the EPP group (median BA/CA = 0.82). Growth velocity improved in the first year of the rhGH therapy in all groups; however, the most significant acceleration was observed in the EPP group (median delta hSDS = 0.9), then stabilised and was comparable in all groups. MRI may be helpful in predicting response to the rhGH treatment, providing midline abnormalities are taken into account.

Analysis of rhG-CSF-effects on platelets by in vitro bleeding test and transcranial Doppler ultrasound examination.

PubMed

Söhngen, D; Wienen, S; Siebler, M; Boogen, C; Scheid, C; Schulz, A; Kobbe, G; Diehl, V; Heyll, A

1998-12-01

Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen.

Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions

PubMed Central

Payne, Ruth O.; Silk, Sarah E.; Elias, Sean C.; Diouf, Ababacar; Galaway, Francis; de Graaf, Hans; Brendish, Nathan J.; Poulton, Ian D.; Griffiths, Oliver J.; Edwards, Nick J.; Jin, Jing; Labbé, Geneviève M.; Alanine, Daniel G.W.; Siani, Loredana; Di Marco, Stefania; Roberts, Rachel; Green, Nicky; Berrie, Eleanor; Ishizuka, Andrew S.; Nielsen, Carolyn M.; Bardelli, Martino; Partey, Frederica D.; Ofori, Michael F.; Barfod, Lea; Wambua, Juliana; Murungi, Linda M.; Osier, Faith H.; Biswas, Sumi; McCarthy, James S.; Minassian, Angela M.; Ashfield, Rebecca; Viebig, Nicola K.; Nugent, Fay L.; Douglas, Alexander D.; Wright, Gavin J.; Faust, Saul N.; Hill, Adrian V.S.; Long, Carole A.; Lawrie, Alison M.; Draper, Simon J.

2017-01-01

The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen to date, capable of conferring protection against stringent challenge in Aotus monkeys. We report on the first clinical trial to our knowledge to assess the RH5 antigen — a dose-escalation phase Ia study in 24 healthy, malaria-naive adult volunteers. We utilized established viral vectors, the replication-deficient chimpanzee adenovirus serotype 63 (ChAd63), and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding RH5 from the 3D7 clone of P. falciparum. Vaccines were administered i.m. in a heterologous prime-boost regimen using an 8-week interval and were well tolerated. Vaccine-induced anti-RH5 serum antibodies exhibited cross-strain functional growth inhibition activity (GIA) in vitro, targeted linear and conformational epitopes within RH5, and inhibited key interactions within the RH5 invasion complex. This is the first time to our knowledge that substantial RH5-specific responses have been induced by immunization in humans, with levels greatly exceeding the serum antibody responses observed in African adults following years of natural malaria exposure. These data support the progression of RH5-based vaccines to human efficacy testing. PMID:29093263

Pulsatile LH secretion and ovarian follicular wave emergence and growth in anestrous ewes.

PubMed

Seekallu, Srinivas V; Barrett, David M W; Toosi, Behzad M; Clarke, Kelsey; Ewen, Kirk A; Duggavathi, Rajesha; Davies, Kate L; Pattullo, Kim M; Bagu, Edward T; Rawlings, Norman C

2010-10-01

The objective of this study was to determine if pulsatile LH secretion was needed for ovarian follicular wave emergence and growth in the anestrous ewe. In Experiment 1, ewes were either large or small (10 x 0.47 or 5 x 0.47 cm, respectively; n = 5/group) sc implants releasing estradiol-17 beta for 10 d (Day 0 = day of implant insertion), to suppress pulsed LH secretion, but not FSH secretion. Five sham-operated control ewes received no implants. In Experiment 2, 12 ewes received large estradiol-releasing implants for 12 d (Day 0 = day of implant insertion); six were given GnRH (200 ng IV) every 4 h for the last 6 d that the implants were in place (to reinitiate pulsed LH secretion) whereas six Control ewes were given saline. Ovarian ultrasonography and blood sampling were done daily; blood samples were also taken every 12 min for 6 h on Days 5 and 9, and on Days 6 and 12 of the treatment period in Experiments 1 and 2, respectively. Treatment with estradiol blocked pulsatile LH secretion (P < 0.001). In Experiment 1, implant treatment halted follicular wave emergence between Days 2 and 10. In Experiment 2, follicular waves were suppressed during treatment with estradiol, but resumed following GnRH treatment. In both experiments, the range of peaks in serum FSH concentrations that preceded and triggered follicular wave emergence was almost the same as control ewes and those given estradiol implants alone or with GnRH; mean concentrations did not differ (P < 0.05). We concluded that some level of pulsatile LH secretion was required for the emergence of follicular waves that were triggered by peaks in serum FSH concentrations in the anestrous ewe. (c) 2010 Elsevier Inc. All rights reserved.

VATS versus intrapleural streptokinase: A prospective, randomized, controlled clinical trial for optimum treatment of post-traumatic Residual Hemothorax.

PubMed

Kumar, S; Rathi, V; Rattan, A; Chaudhary, S; Agarwal, N

2015-09-01

Post-traumatic residual haemothorax (RH) is common and carries significant morbidity. However, its optimal treatment is not clear. The aim of this study was to find the extent of this problem and the choice of treatment between VATS and intra-pleural streptokinase instillation (IPSI). This RCT, conducted over 18 months period, included all patients of chest trauma between 18 and 70 years of age, admitted with haemothorax or haemopneumothorax requiring inter-costal drain (ICD) insertion. 154 events of haemothorax/haemopneumothorax requiring ICD insertion were enrolled. RH was seen in 48 (31%) patients: 13 patients were excluded from RCT after refusal for treatment. Seventeen (49%) patients of remaining 35 RH cases were randomized to IPSI group and 18 (51%) patients were randomized to VATS group. The outcome parameters were resolution of RH and treatment related complications. RH resolved equally well in VATS and IPSI group [13 patients (72%) versus 12 patients (71%), respectively; continuity-adjusted p=1]. Morbidity wise no difference (p-value 0.529) was seen in the two groups. Post-traumatic RH is seen in 1/3rd patients and is equally well treated by VATS and IPSI. Copyright © 2015 Elsevier Ltd. All rights reserved.

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.

PubMed

Wong, S C; Kumar, P; Galloway, P J; Blair, J C; Didi, M; Dalzell, A M; Hassan, K; McGrogan, P; Ahmed, S Faisal

2011-05-01

It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status. © 2011 Blackwell Publishing Ltd.

Inductive potential of recombinant human granulocyte colony-stimulating factor to mature neutrophils from x-irradiated human peripheral blood hematopoietic progenitor cells.

PubMed

Katsumori, Takeo; Yoshino, Hironori; Hayashi, Masako; Takahashi, Kenji; Kashiwakura, Ikuo

2009-11-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been used for treatment of neutropenia. Filgrastim, Nartograstim, and Lenograstim are clinically available in Japan. However, the differences in potential benefit for radiation-induced disorder between these types of rhG-CSFs remain unknown. Therefore, the effects of three different types of rhG-CSFs on granulocyte progenitor cells and expansion of neutrophils from nonirradiated or 2 Gy X-irradiated human CD34+ hematopoietic progenitor cells were examined. For analysis of granulocyte colony-forming units (CFU-G) and a surviving fraction of CFU-G, nonirradiated or X-irradiated CD34+ cells were cultured in methylcellulose containing rhG-CSF. These cells were cultured in serum-free medium supplemented with rhG-CSF, and the expansion and characteristics of neutrophils were analyzed. All three types of rhG-CSFs increased the number of CFU-G in a dose-dependent manner; however, Lenograstim is superior to others because of CFU-G-derived colony formation at relatively low doses. The surviving fraction of CFU-G was independent of the types of rhG-CSFs. Expansion of neutrophils by rhG-CSF was largely attenuated by X-irradiation, though no significant difference in neutrophil number was observed between the three types of rhG-CSFs under both nonirradiation and X-irradiation conditions. In terms of functional characteristics of neutrophils, Lenograstim-induced neutrophils produced high levels of reactive oxygen species compared to Filgrastim, when rhG-CSF was applied to nonirradiated CD34(+) cells. In conclusion, different types of rhG-CSFs lead to different effects when rhG-CSF is applied to nonirradiated CD34+ cells, though Filgrastim, Nartograstim, and Lenograstim show equal effects on X-irradiated CD34+ cells.

Surgical stabilization of severe rib fractures decreases incidence of retained hemothorax and empyema.

PubMed

Majercik, Sarah; Vijayakumar, Sathya; Olsen, Griffin; Wilson, Emily; Gardner, Scott; Granger, Steven R; Van Boerum, Don H; White, Thomas W

2015-12-01

Retained hemothorax (RH) is relatively common after chest trauma and can lead to empyema. We hypothesized that patients who have surgical fixation of rib fractures (SSRF) have less RH and empyema than those who have medical management of rib fractures (MMRF). Admitted rib fracture patients from January 2009 to June 2013 were identified. A 2:1 propensity score model identified MMRF patients who were similar to SSRF. RH, and empyema and readmissions, were recorded. Variables were compared using Fisher exact test and Wilcoxon rank-sum tests. One hundred thirty-seven SSRF and 274 MMRF were analyzed; 31 (7.5%) had RH requiring 35 interventions; 3 (2.2%) SSRF patients had RH compared with 28 (10.2%) MMRF (P = .003). Four (14.3%) MMRF subjects with RH developed empyema versus zero in the SSRF group (P = .008); 6 (19.3%) RH patients required readmission versus 14 (3.7%) in the non-RH group (P = .002). Patients with rib fractures who have SSRF have less RH compared with similar MMRF patients. Although not a singular reason to perform SSRF, this clinical benefit should not be overlooked. Copyright © 2015 Elsevier Inc. All rights reserved.

Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter.

PubMed

Nieuwlaat, Willy-Anne; Huysmans, Dyde A; van den Bosch, Harrie C; Sweep, C G Fred; Ross, H Alec; Corstens, Frans H; Hermus, Ad R

2003-07-01

In patients with nodular goiter, radioiodine ((131)I) therapy results in a mean reduction in thyroid volume (TV) of approximately 40% after 1 yr. We have demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h radioactive iodine uptake (RAIU) in these patients. We have now studied the safety and efficacy of therapy with a reduced dose of (131)I after pretreatment with rhTSH. Twenty-two patients with nodular goiter received (131)I therapy, 24 h after im administration of 0.01 (n = 12) or 0.03 (n = 10) mg rhTSH. In preceding diagnostic studies using tracer doses of (131)I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of (131)I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 micro Ci/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of (131)I therapy by a factor of 1.9 +/- 0.5 in the 0.01-mg and by a factor of 2.4 +/- 0.4 in the 0.03-mg rhTSH group (P < 0.05, 0.01 vs. 0.03 mg rhTSH). Before and 1 yr after therapy, TV and the smallest cross-sectional area of the tracheal lumen were measured with magnetic resonance imaging. During the year of follow-up, serum TSH, free T(4) (FT(4)), T(3), and TSH receptor antibodies were measured at regular intervals. TV before therapy was 143 +/- 54 ml in the 0.01-mg group and 103 +/- 44 ml in the 0.03-mg rhTSH group. One year after treatment, TV reduction was 35 +/- 14% (0.01 mg rhTSH) and 41 +/- 12% (0.03 mg rhTSH). In both groups, smallest cross-sectional area of the tracheal lumen increased significantly. In the 0.01-mg rhTSH group, serum FT(4) rose, after (131)I treatment, from 15.8 +/- 2.8 to 23.2 +/- 4.4 pM. In the 0.03-mg rhTSH group, serum FT(4) rose from 15.5 +/- 2.5 to 23.5 +/- 5.1 pM. Individual peak FT(4) levels, reached between 1 and 28 d after (131)I treatment, were above the normal range in 12 patients. TSH receptor antibodies were negative in all patients before therapy and became positive in 4 patients. Hyperthyroidism developed in 3 of these 4 patients between 23 and 25 wk after therapy. In conclusion, in patients with nodular goiter pretreatment with a single, low dose of rhTSH allowed approximately 50-60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of TV reduction.

Defibrotide in combination with granulocyte colony-stimulating factor significantly enhances the mobilization of primitive and committed peripheral blood progenitor cells in mice.

PubMed

Carlo-Stella, Carmelo; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Stucchi, Claudio; Cleris, Loredana; Formelli, Franca; Gianni, Massimo A

2002-11-01

Defibrotide is a polydeoxyribonucleotide, which significantly reduces the expression of adhesion molecules on endothelial cells. We investigated the activity of Defibrotide alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize peripheral blood progenitor cells (PBPCs) in BALB/c mice. A 5-day treatment with Defibrotide alone (1-15 mg/mouse/day) had no effect on WBC counts, frequencies and absolute numbers of total circulating colony-forming cells (CFCs), i.e., granulocyte-macrophage colony-forming units, erythroid burst-forming units, and multilineage colony-forming units. As compared with mock-injected mice, administration of rhG-CSF alone (5 micro g/mouse/day) for 5 days significantly (P < or = 0.0001) increased WBC counts, CFC frequencies, and CFC absolute numbers by 2-, 13-, and 27-fold, respectively. As compared with control mice, the combined administration of Defibrotide (15 mg/mouse/day) and rhG-CSF significantly (P < or = 0.0001) increased WBC counts, frequencies and absolute numbers of CFCs by 4-, 38-, and 119-fold, respectively. As compared with rhG-CSF alone, administration of Defibrotide plus rhG-CSF resulted in a significant increase (P < or = 0.001) of the frequency of circulating long-term culture-initiating cells. In addition, transplantation of 2 x 10(5) rhG-CSF- or Defibrotide/rhG-CSF-mobilized mononuclear cells rescued 43% and 71% of recipient mice, respectively. Experiments of CFC homing performed in lethally irradiated or nonirradiated recipients showed that marrow homing of transplanted PBPCs was reduced by 3-fold in Defibrotide-treated animals as compared with mock-injected mice (P < or = 0.001), suggesting that the mobilizing effect of Defibrotide might be because of an effect on PBPC trafficking. In conclusion, our data demonstrate that Defibrotide synergizes with rhG-CSF and significantly increases the mobilization of a broad spectrum of PBPCs, including primitive and committed progenitor cells. These data might have relevant implications for autologous and allogeneic anticancer therapy in humans.

Increased pulse pressure is associated with left atrial enlargement in resistant hypertensive patients.

PubMed

Armario, Pedro; Oliveras, Anna; Hernández-Del-Rey, Raquel; Suárez, Carmen; Martell, Nieves; Ruilope, Luis M; De La Sierra, Alejandro

2013-02-01

Resistant hypertension (RH) is frequently associated with a high prevalence of target organ damage, which impairs the prognosis of these patients. Considering cardiac alterations in RH, most attention has been devoted to left ventricular hypertrophy (LVH), but data concerning left atrial enlargement (LAE) is less known. This cross-sectional study assessed the factors associated with LAE, with special focus on blood pressure (BP) estimates obtained by ambulatory blood pressure monitoring (ABPM), in 250 patients with RH, aged 64 ± 11 years. LAE and LVH were observed in 10.0% (95% CI 6.3-13.7) and 57.1% (95% CI 50.8-63.5) of patients, respectively. Compared with patients with normal atrium size, those exhibiting LAE were older, more frequently women, had elevated pulse pressure (PP) measured both at the office and by ABPM, and showed higher prevalence of LVH (83% vs 54%; p = 0.016). In a logistic regression analysis, adjusting for age, gender, body mass index, left ventricular mass index and BP pressure estimates, night-time PP was independently associated with LAE (OR for 5 mmHg = 1.28, 95% CI 1.24-1.32; p = 0.001). In conclusion, besides classical determinants of LAE, such as age and LVH, an elevated night-time PP was independently associated with LAE in patients with RH.

Peripheral blood stem cell mobilization and engraftment after autologous stem cell transplantation with biosimilar rhG-CSF.

PubMed

Reményi, Péter; Gopcsa, László; Marton, Imelda; Réti, Marienn; Mikala, Gábor; Pető, Mónika; Barta, Anikó; Bátai, Arpád; Farkas, Zita; Borbényi, Zita; Csukly, Zoltán; Bodó, Imre; Fábián, János; Király, Agnes; Lengyel, Lilla; Piukovics, Klára; Torbágyi, Eva; Masszi, Tamás

2014-04-01

Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen(®)], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio(®), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 × 5 μg) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU(®), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 × 10(6)/kg (2.22-57.07 × 10(6)/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 × 10(6)/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients. In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.

Trends of reactive hyperaemia responses to repetitive loading on skin tissue of rats - Implications for pressure ulcer prevention.

PubMed

Yapp, Jong-Heng; Kamil, Raja; Rozi, M; Mohtarrudin, Norhafizah; Loqman, M Y; Ezamin, A R; Ahmad, Siti Anom; Abu Bakar, Zuki

2017-08-01

Tissue recovery is important in preventing tissue deterioration, which is induced by pressure and may lead to pressure ulcers (PU). Reactive hyperaemia (RH) is an indicator used to identify people at risk of PU. In this study, the effect of different recovery times on RH trend is investigated during repetitive loading. Twenty-one male Sprague-Dawley rats (seven per group), with body weight of 385-485 g, were categorised into three groups and subjected to different recovery times with three repetitive loading cycles. The first, second, and third groups were subjected to short (3 min), moderate (10 min), and prolonged (40 min) recovery, respectively, while fixed loading time and pressure (10 min and 50 mmHg, respectively). Peak hyperaemia was measured in the three cycles to determine trends associated with different recovery times. Three RH trends (increasing, decreasing, and inconsistent) were observed. As the recovery time is increased (3 min vs. 10 min vs. 40 min), the number of samples with increasing RH trend decreases (57% vs. 29% vs. 14%) and the number of samples with inconsistent RH trend increases (29% vs. 57% vs. 72%). All groups consists of one sample with decreasing RH trend (14%). Results confirm that different recovery times affect the RH trend during repetitive loading. The RH trend may be used to determine the sufficient recovery time of an individual to avoid PU development. Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

In vitro and in vivo evaluation of osteoinductivity and bone fusion ability of an activin a/BMP2 chimera (AB204): a comparison study between AB204 and rhBMP-2.

PubMed

Zheng, Guang Bin; Lee, Jae Hyup; Jin, Yuan-Zhe

2017-12-01

This study compared osteoinductivity and osteogenic capacity between AB204 and rhBMP-2 using hMSCs in vitro and a beagle's posterolateral spinal fusion model. Cultured hMSCs were treated with AB204 or rhBMP-2 with low to high doses. Three male beagles were performed posterolateral spinal fusion with biphasic calcium phosphate (2 ml) + AB204 or rhBMP-2 (20, 50 or 200 µg). They were euthanized after 8 weeks. The fusion rate and bone formation of spine samples were examined. AB204 had higher alkaline phosphatase activity, mineralization and osteogenic-related gene expression than rhBMP-2. Fusion rates in all rhBMP-2 groups were 0. They were 100% for 50 μg and 200 μg AB204 groups. Therefore, AB204 showed higher osteogenicity than rhBMP-2. It could be a better bone graft substitute.

[Slow-release recombinant human bone morphogenetic protein-2 suppresses chromium wear particle-induced osteolysis in rats].

PubMed

Li, Gan; Li, Qi; Lin, Li-Jun; Duan, Xin; Zhang, Xi-Qi

2012-03-01

To observe the effect of a slow-release recombinant human bone morphogenetic protein-2 (rhBMP-2) formulation on the expressions of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in a murine air pouch model of bone implantation. A cranial bone allograft was implanted in the air pouch induced on the back of the recipients. The rat models were then randomized into 5 groups, including a blank control group, chromium particle group, and 3 rhBMP-2 groups receiving 50, 100 or 200 µg/L slow-release rhBMP-2 in addition to chromium particles. Three weeks later, the expressions of RANKL and OPG in the air pouch was detected using Western blotting and RT-PCR, and the positively stained area for osteoclasts in the bone graft was determined with TRAP staining for drug effect assessment. RANKL and OPG expressions were found in the air pouches in all the 5 groups. RANKL and OPG protein and mRNA expressions, RANKL/OPG ratio and osteoclast staining area in the bone graft were the highest in chromium particle group (P<0.05), but were significantly decreased by treatment with the slow-release rhBMP-2 formulation (P<0.05); the measurements showed no significant differences between the blank control group and 200 µg/L rhBMP-2 group (P>0.05). Chromium particles can cause osteolysis by increasing the RANKL/OPG ratio in rats, and intervention with slow-release rhBMP-2 can significantly promote bone formation and suppress bone resorption by decreasing RANKL/OPG ratio.

Functional Reconstitution into Liposomes of Purified Human RhCG Ammonia Channel

PubMed Central

Mouro-Chanteloup, Isabelle; Cochet, Sylvie; Chami, Mohamed; Genetet, Sandrine; Zidi-Yahiaoui, Nedjma; Engel, Andreas; Colin, Yves; Bertrand, Olivier; Ripoche, Pierre

2010-01-01

Background Rh glycoproteins (RhAG, RhBG, RhCG) are members of the Amt/Mep/Rh family which facilitate movement of ammonium across plasma membranes. Changes in ammonium transport activity following expression of Rh glycoproteins have been described in different heterologous systems such as yeasts, oocytes and eukaryotic cell lines. However, in these complex systems, a potential contribution of endogenous proteins to this function cannot be excluded. To demonstrate that Rh glycoproteins by themselves transport NH3, human RhCG was purified to homogeneity and reconstituted into liposomes, giving new insights into its channel functional properties. Methodology/Principal Findings An HA-tag introduced in the second extracellular loop of RhCG was used to purify to homogeneity the HA-tagged RhCG glycoprotein from detergent-solubilized recombinant HEK293E cells. Electron microscopy analysis of negatively stained purified RhCG-HA revealed, after image processing, homogeneous particles of 9 nm diameter with a trimeric protein structure. Reconstitution was performed with sphingomyelin, phosphatidylcholine and phosphatidic acid lipids in the presence of the C12E8 detergent which was subsequently removed by Biobeads. Control of protein incorporation was carried out by freeze-fracture electron microscopy. Particle density in liposomes was a function of the Lipid/Protein ratio. When compared to empty liposomes, ammonium permeability was increased two and three fold in RhCG-proteoliposomes, depending on the Lipid/Protein ratio (1/300 and 1/150, respectively). This strong NH3 transport was reversibly inhibited by mercuric and copper salts and exhibited a low Arrhenius activation energy. Conclusions/Significance This study allowed the determination of ammonia permeability per RhCG monomer, showing that the apparent PunitNH3 (around 1×10−3 µm3.s−1) is close to the permeability measured in HEK293E cells expressing a recombinant human RhCG (1.60×10−3 µm3.s−1), and in human red blood cells endogenously expressing RhAG (2.18×10−3 µm3.s−1). The major finding of this study is that RhCG protein is active as an NH3 channel and that this function does not require any protein partner. PMID:20126667

Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

PubMed

Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

2015-12-01

Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Combined application of alginate dressing and human granulocyte-macrophage colony stimulating factor promotes healing in refractory chronic skin ulcers.

PubMed

Huang, Guobao; Sun, Tangqing; Zhang, Lei; Wu, Qiuhe; Zhang, Keyan; Tian, Qingfen; Huo, Ran

2014-06-01

The aim of the present study was to evaluate the clinical therapeutic effect of the combined application of alginate and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the healing of refractory chronic skin ulcers. A single center, three arm, randomized study was performed at Jinan Central Hospital (Jinan, Shandong, China). A total of 60 patients with refractory chronic skin ulcers, which persisted for >1 month, were enrolled and randomly assigned into one of the following three groups: alginate dressing/rhGM-CSF group (group A), rhGM-CSF only group (group B) and conventional (vaseline dressing) group (group C). The wound area rate was measured, granulation and color were observed and pain was evaluated. The data were summarized and statistical analysis was performed. The results demonstrated that group A exhibited a significantly faster wound healing rate and lower pain score compared with the other groups (P<0.01). In conclusion, the combined application of alginate dressing and rhGM-CSF for the treatment of refractory chronic skin ulcers demonstrated significant advantages. It promoted the growth of granulation tissue, accelerated re-epithelialization and also effectively reduced wound pain, and thus improved the quality of life for the patient. This suggests that the combined application of alginate and rhGM-CSF may be an effective therapeutic strategy for the clinical treatment of refractory chronic skin ulcers.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF.

PubMed

Çelik, Gayem İnayet Turgay; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

2015-01-01

To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). The combination protocol does not provide additional efficacy.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF

PubMed Central

Turgay Çelik, Gayem İnayet; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

2015-01-01

Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). Conclusion. The combination protocol does not provide additional efficacy. PMID:26161425

Local rhBMP-12 on an Absorbable Collagen Sponge as an Adjuvant Therapy for Rotator Cuff Repair - A Phase 1, Randomized, Standard of Care Control, Multicenter Study: Safety and Feasibility.

PubMed

Greiner, Stefan; Ide, Junji; Van Noort, Arthur; Mochizuki, Yu; Ochi, Hiroshi; Marraffino, Shannon; Sridharan, Sudhakar; Rudicel, Sally; Itoi, Eiji

2015-08-01

Recombinant human bone morphogenetic protein-12 (rhBMP-12) has been shown to induce tendon and ligament formation in rats and to improve tendon healing; however, the safety and feasibility of implanting rhBMP-12/absorbable collagen sponge (ACS) in humans are not known. To investigate the safety and feasibility of rhBMP-12 on an ACS as an adjuvant therapy in open rotator cuff repair. Randomized controlled trial; Level of evidence, 2. This study consisted of 20 patients with full-thickness rotator cuff tears. Patients were randomized either to standard of care (SOC) treatment (open rotator cuff repair) or to receive 0.015 mg/mL rhBMP-12/ACS and SOC treatment during their open rotator cuff repair (rhBMP-12/ACS group) at a rate of 1/4 SOC/rhBMP-12/ACS. The feasibility of implanting the product and the safety of the product were evaluated during the 1-year follow-up period. The evaluation involved up to 10 postoperative visits, which included physical examinations, radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans with an emphasis on heterotopic ossification (HO), pharmacokinetics, immunogenicity, laboratory evaluations, and local and systemic adverse events at specified time points. Small amounts of HO were seen on follow-up CT scans in 10 of 16 patients in the rhBMP-12/ACS group and in 2 of 3 patients in the SOC group. HO did not increase at 26 weeks and was not associated with any adverse events or unsatisfactory clinical outcomes. Pharmacokinetics demonstrated that circulating levels of rhBMP-12 were not detectable after administration. Five of 16 patients showed a postoperative immunogenic response but did not show any correlating adverse events. Complete healing of the rotator cuff was observed in 14 of 16 patients; 2 of 16 imaging results could not be analyzed because of artifacts in the rhBMP-12 group on MRI scans. In the SOC group, 1 of 4 patients showed a retear at 12 weeks after surgery. The use of rhBMP-12/ACS has been shown to be feasible and safe in a concentration of 0.015 mg/mL when used in open rotator cuff repair. Higher dose concentrations of rhBMP-12 should be evaluated in the future to evaluate their safety and potential to increase rotator cuff healing after open surgical repair. © 2015 The Author(s).

[Differential regulation of CCR5 expression on T lymphocytes in healthy donors after mobilization with rhG-CSF and its correlation with aGVHD].

PubMed

Wang, Meng; Ma, Xiang-Juan; Dong, Yu-Jun; Qiu, Zhi-Xiang; Liu, Wei; Li, Yuan; Wang, Mang-Ju; Sun, Yu-Hua; Ren, Han-Yun

2013-08-01

This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. The expression of CCR5 on CD4(+) and CD8(+) T cells in the peripheral blood (PB) before and after mobilization were detected by using flow cytometry (FCM) respectively. According to the changes of CCR5 expression on CD4(+) and CD8(+) T cells, the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated (non-downregulated) groups, and the incidence of grades II to IV aGVHD in two groups were compared. The results showed that the mean value of CCR5 expression on CD4(+) and CD8(+) T cells in PB was not different significantly after mobilization (P > 0.05). Apparent inconsistency was showed among different individuals. Thirty-four (50%) donors displayed downregulation of CCR5 expression, while 34 (50%) donors manifested unchanged or upregulated CCR5 expression on CD4(+) T cells. CCR5 expression on CD8(+) T cells was downregulated in 42 (61.8%), unchanged or upregulated in 26 (38.3%) donors. The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4(+) T cells were 16.1% and 41.9% (P = 0.032), and recipients with CCR5 downregulation on CD8(+) T cells showed an increased tendency of developing aGVHD (37.8% vs 16.0%, P = 0.065). In conclusion, rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells, which might influence the migration of T cells in vivo, decrease T cell trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation.

The influence of exogenous progestin on the occurrence of proestrous or estrous signs, plasma concentrations of luteinizing hormone and estradiol in deslorelin (GnRH agonist) treated anestrous bitches.

PubMed

Sung, M; Armour, A F; Wright, P J

2006-10-01

The objectives of this study were to confirm: (i) whether progestin treatment suppressed GnRH agonist-induced estrus in anestrous greyhound bitches; and (ii) the site of progestin action (i.e. pituitary, ovary). All bitches received a deslorelin implant on Day 0 and blood samples were taken from -1 h to +6 h. Five bitches were treated with megestrol acetate (2 mg/kg orally once daily) from -7 d to +6 d (Group 1) and 10 bitches were untreated controls (Group 2). Proestrous or estrous signs were observed in 4 of 5 bitches in Group 1, and 4 of 10 bitches in Group 2 (P = 0.28). The plasma LH responses (area under the curve from 0 to 6h after implantation) were higher (P = 0.008) in Group 2 than in Group 1. Plasma LH responses were similar (P = 0.59) in bitches showing signs of proestrus or estrus (responders) and in non-responders. The plasma estradiol responses (calculated as for LH response) were greater in Group 1 than in Group 2 (P = 0.048), and in responders than in non-responders (P = 0.02). (i) progestin treatment (a) did not suppress the incidence of bitches showing deslorelin-induced proestrus or estrus, and (b) was associated with a reduced pituitary responsiveness and an increased ovarian responsiveness to deslorelin treatment; (ii) the occurrence of proestrous or estrous signs reflected increased ovarian responsiveness to induced gonadotrophin secretion and not increased pituitary responsiveness to deslorelin.

Pre-Analytical Conditions in Non-Invasive Prenatal Testing of Cell-Free Fetal RHD

PubMed Central

Rieneck, Klaus; Krog, Grethe Risum; Nielsen, Leif Kofoed; Tabor, Ann; Dziegiel, Morten Hanefeld

2013-01-01

Background Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women. In Denmark, routine antenatal screening for the fetal RhD gene (RHD) directs the administration of antenatal anti-D prophylaxis only to women who carry an RhD positive fetus. Prophylaxis reduces the risk of immunization that may lead to hemolytic disease of the fetus and the newborn. The reliability of predicting the fetal RhD type depends on pre-analytical factors and assay sensitivity. We evaluated the testing setup in the Capital Region of Denmark, based on data from routine antenatal RHD screening. Methods Blood samples were drawn at gestational age 25 weeks. DNA extracted from 1 mL of plasma was analyzed for fetal RHD using a duplex method for exon 7/10. We investigated the effect of blood sample transportation time (n = 110) and ambient outdoor temperatures (n = 1539) on the levels of cffDNA and total DNA. We compared two different quantification methods, the delta Ct method and a universal standard curve. PCR pipetting was compared on two systems (n = 104). Results The cffDNA level was unaffected by blood sample transportation for up to 9 days and by ambient outdoor temperatures ranging from -10°C to 28°C during transport. The universal standard curve was applicable for cffDNA quantification. Identical levels of cffDNA were observed using the two automated PCR pipetting systems. We detected a mean of 100 fetal DNA copies/mL at a median gestational age of 25 weeks (range 10–39, n = 1317). Conclusion The setup for real-time PCR-based, non-invasive prenatal testing of cffDNA in the Capital Region of Denmark is very robust. Our findings regarding the transportation of blood samples demonstrate the high stability of cffDNA. The applicability of a universal standard curve facilitates easy cffDNA quantification. PMID:24204719

Pre-analytical conditions in non-invasive prenatal testing of cell-free fetal RHD.

PubMed

Clausen, Frederik Banch; Jakobsen, Tanja Roien; Rieneck, Klaus; Krog, Grethe Risum; Nielsen, Leif Kofoed; Tabor, Ann; Dziegiel, Morten Hanefeld

2013-01-01

Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women. In Denmark, routine antenatal screening for the fetal RhD gene (RHD) directs the administration of antenatal anti-D prophylaxis only to women who carry an RhD positive fetus. Prophylaxis reduces the risk of immunization that may lead to hemolytic disease of the fetus and the newborn. The reliability of predicting the fetal RhD type depends on pre-analytical factors and assay sensitivity. We evaluated the testing setup in the Capital Region of Denmark, based on data from routine antenatal RHD screening. Blood samples were drawn at gestational age 25 weeks. DNA extracted from 1 mL of plasma was analyzed for fetal RHD using a duplex method for exon 7/10. We investigated the effect of blood sample transportation time (n = 110) and ambient outdoor temperatures (n = 1539) on the levels of cffDNA and total DNA. We compared two different quantification methods, the delta Ct method and a universal standard curve. PCR pipetting was compared on two systems (n = 104). The cffDNA level was unaffected by blood sample transportation for up to 9 days and by ambient outdoor temperatures ranging from -10 °C to 28 °C during transport. The universal standard curve was applicable for cffDNA quantification. Identical levels of cffDNA were observed using the two automated PCR pipetting systems. We detected a mean of 100 fetal DNA copies/mL at a median gestational age of 25 weeks (range 10-39, n = 1317). The setup for real-time PCR-based, non-invasive prenatal testing of cffDNA in the Capital Region of Denmark is very robust. Our findings regarding the transportation of blood samples demonstrate the high stability of cffDNA. The applicability of a universal standard curve facilitates easy cffDNA quantification.

Aerobic Exercise Training and Arterial Changes in African-Americans versus Caucasians

PubMed Central

Ranadive, Sushant M.; Yan, Huimin; Lane, Abbi D.; Kappus, Rebecca M.; Cook, Marc D.; Sun, Peng; Harvey, Idethia; Ploutz-Synder, Robert; Woods, Jeffrey A.; Wilund, Kenneth R.; Fernhall, Bo

2015-01-01

African-Americans (AA) have increased carotid artery intima-media thickness and decreased vascular function compared to their Caucasian (CA) peers. Aerobic exercise prevents and potentially reverses arterial dysfunction. Purpose The purpose of this study was to examine the effect of 8 weeks of moderate-high intensity aerobic training in young healthy sedentary AA and CA men and women. Methods Sixty-four healthy volunteers (men = 28, women = 36) with mean age = 24 underwent measures of arterial structure, function and blood pressure variables at baseline, post-4 week control period and 8 weeks post-training. Results There was a significant increase in VO2peak amongst both groups post exercise training. Brachial systolic blood pressure decreased significantly following control period in both groups but not following exercise training. Carotid pulse pressure decreased significantly in both groups post exercise training as compared to baseline. There was no change in any of the other blood pressure variables. AAs had a higher intima-media thickness at baseline and post-control period, but significantly decreased following exercise training compared to CAs. AAs had significantly lower baseline forearm blood flow and RH compared to CAs, but exercise training had no effect on these variables. There was no significant difference in arterial stiffness (cPWV) and wave-reflection (AIx) between the two groups at any time point. Conclusions This is the first study to show that, 8 weeks of aerobic exercise training causes significant improvement in the arterial structure in young, healthy AAs, making it comparable to the CAs and with minimal effects on blood pressure variables. PMID:26225767

Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols.

PubMed

Toftager, M; Bogstad, J; Løssl, K; Prætorius, L; Zedeler, A; Bryndorf, T; Nilas, L; Pinborg, A

2017-03-01

Are cumulative live birth rates (CLBRs) similar in GnRH-antagonist and GnRH-agonist protocols for the first ART cycle including all subsequent frozen-thaw cycles from the same oocyte retrieval? The chances of at least one live birth following utilization of all fresh and frozen embryos after the first ART cycle are similar in GnRH-antagonist and GnRH-agonist protocols. Reproductive outcomes of ART treatment are traditionally reported as pregnancies per cycle or per embryo transfer. However, the primary concern is the overall chance of a live birth. After the first ART cycle with fresh embryo transfer, we found live birth rates (LBRs) of 22.8% and 23.8% (P = 0.70) for the GnRH-antagonist and GnRH-agonist protocols, respectively. But with CLBRs including both fresh and frozen embryos from the first oocyte retrieval, chances of at least one live birth increases. There are no previous randomized controlled trials (RCTs) comparing CLBRs in GnRH-antagonist versus GnRH-agonist protocols. Previous studies on CLBR are either retrospective cohort studies including multiple fresh cycles or RCTs comparing single embryo transfer (SET) with double embryo transfer (DET). CLBR was a secondary outcome in a Phase IV, dual-center, open-label, RCT including 1050 women allocated to a short GnRH-antagonist or a long GnRH-agonist protocol in a 1:1 ratio over a 5-year period using a web-based concealed randomization code. The minimum follow-up time from the first IVF cycle was 2 years. The aim was to compare CLBR between the two groups following utilization of all fresh and frozen embryos from the first ART cycle. All women referred for their first ART cycle at two public fertility clinics, <40 years of age were approached. A total of 1050 subjects were allocated to treatment and 1023 women started standardized ART protocols with recombinant human follitropin-β (rFSH) stimulation. Day-2 SET was planned and additional embryos were frozen and used in subsequent frozen-thawed cycles. All pregnancies generated from oocyte retrieval during the first IVF cycle including fresh and frozen-thaw cycles were registered. Ongoing pregnancy was determined by ultrasonography at gestational week 7-9 and live birth was irrespective of the duration of gestation. CLBR was defined as at least one live birth per allocated woman after fresh and frozen cycles. Subjects were censored out after the first live birth. Cox proportional hazard model was used to evaluate the relative prognostic significance of female age, BMI, the number of retrieved oocytes and the diagnosis of infertility in relation to the CLBR. Baseline characteristics were similar and equal proportions of patients continued with frozen-thaw (frozen embryo transfer, FET) cycles after their fresh ART cycle in the GnRH-antagonist and GnRH-agonist arms. When combining all fresh and frozen-thaw embryo transfers from first oocyte retrieval with a minimum of 2-year follow-up, the CLBR was 34.1% (182/534) in the GnRH-antagonist group versus 31.2% (161/516) in the GnRH-agonist group (odds ratio (OR):1.14; 95% CI: 0.88-1.48, P = 0.32). Mean time to the first live birth was 11.0 months in the GnRH-antagonist group compared to 11.5 months in the GnRH-agonist group (P < 0.01). The total number of deliveries from all FET cycles where embryos were thawed were higher in the antagonist group 64/330 (19.4%) compared to the agonist group 43/355 (12.1%) ((OR): 1.74; 95% CI: 1.14-2.66, P = 0.01). The evaluation of prognostic factors showed that more retrieved oocytes were associated with a significantly higher CLBR in both treatment groups. For the subgroup of obese women (BMI >30 kg/m2), the CLBR was significantly higher in the GnRH-antagonist group (P = 0.02). The duration of the trial is a possible limitation with introduction of new methods as 'Freeze all' and 'GnRH-agonist triggering', but as these treatments were used in only few women, a systematic bias is not likely. Blastocyst culture of surplus embryos for freezing was introduced to both groups simultaneously, thereby minimizing the risk of bias. Furthermore, with a minimum of 2-year follow-up, a minority (<1%) still had cryopreserved embryos and no live birth at the end of the trial. The post hoc prognostic covariate analyses with multiple strata should be interpreted with caution. Finally, the physicians were not blinded to GnRH treatment group after randomization. With the improvement of embryo culture, freezing and thawing methods as well as a strategy of elective SET, CLBR until first live birth provides an all-inclusive success rate for ART. When comparing GnRH-antagonist and GnRH-agonist protocols, we find similar CLBRs, despite more oocytes being retrieved in the GnRH-agonist protocol. An unrestricted research grant is funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. 18 September 2008. 14 January 2009. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Rectal Hyposensitivity Is Associated With a Defecatory Disorder But Not Delayed Colon Transit Time in a Functional Constipation Population

PubMed Central

Yu, Ting; Qian, Dong; Zheng, Yongping; Jiang, Ya; Wu, Ping; Lin, Lin

2016-01-01

Abstract The physiological mechanism of functional constipation (FC) includes defecatory disorders and delayed colon transit. About 18% to 68% constipated patients may have rectal hyposensitivity (RH). We performed this study to investigate the association between RH and functional defecatory disorder (FDD) as well as that between RH and delayed colon transit in FC patients. A total of 218 FC patients were enrolled. The constipation severity instrument (CSI) was used to assess constipation symptoms. High-resolution anorectal manometry (HR-ARM), defecography, balloon expulsion tests, and colon transit studies were performed for each patient. RH was defined as 1 or more sensory threshold pressures raised beyond the normal range based on HR-ARM. We investigated the association between RH and constipation symptoms, and the occurrence of FDD and delayed CTT. Ninety FDD patients completed the initial phase of biofeedback treatment (BFT). We investigated the association between RH and the effect of BFT. Totally 122 (56.0%) patients had RH. The total CSI (49.82 ± 1.09 vs 41.25 ± 1.55, P = 0.023) and obstructive defecation subscale scores (23.19 ± 0.69 vs 17.07 ± 0.90, P < 0.001) were significantly higher in RH than in non-RH patients. No significant difference was observed in slow transit symptoms (21.77 ± 0.72 vs 19.90 ± 0.85, P = 0.121) or abdominal pain (6.85 ± 2.61 vs 5.00 ± 1.04, P = 0.380). The frequency of prolonged CTT was not significantly different between RH and non-RH groups (54.1% vs 58.3%, P = 0.403). RH patients rated more occurrence of FDD (72.1% vs 53.1%, P = 0.014) and dysynergic defecation (79.8% vs 50.2%, P = 0.004) than non-RH patients, whereas no differences were seen for inadequate defecatory propulsion (59.2% vs 55.0%, P = 0.589). After BFT, the proportion of “no effect” was significantly higher in the RH group than in the non-RH group (22.4% vs 9.4%, P = 0.010). RH is associated with obstructive defecation symptoms and the occurrence of FDD. Further studies are needed to detect the mechanism of RH's effect on BFT and FC. PMID:27175697

Rectal Hyposensitivity Is Associated With a Defecatory Disorder But Not Delayed Colon Transit Time in a Functional Constipation Population.

PubMed

Yu, Ting; Qian, Dong; Zheng, Yongping; Jiang, Ya; Wu, Ping; Lin, Lin

2016-05-01

The physiological mechanism of functional constipation (FC) includes defecatory disorders and delayed colon transit. About 18% to 68% constipated patients may have rectal hyposensitivity (RH). We performed this study to investigate the association between RH and functional defecatory disorder (FDD) as well as that between RH and delayed colon transit in FC patients.A total of 218 FC patients were enrolled. The constipation severity instrument (CSI) was used to assess constipation symptoms. High-resolution anorectal manometry (HR-ARM), defecography, balloon expulsion tests, and colon transit studies were performed for each patient. RH was defined as 1 or more sensory threshold pressures raised beyond the normal range based on HR-ARM. We investigated the association between RH and constipation symptoms, and the occurrence of FDD and delayed CTT. Ninety FDD patients completed the initial phase of biofeedback treatment (BFT). We investigated the association between RH and the effect of BFT.Totally 122 (56.0%) patients had RH. The total CSI (49.82 ± 1.09 vs 41.25 ± 1.55, P = 0.023) and obstructive defecation subscale scores (23.19 ± 0.69 vs 17.07 ± 0.90, P < 0.001) were significantly higher in RH than in non-RH patients. No significant difference was observed in slow transit symptoms (21.77 ± 0.72 vs 19.90 ± 0.85, P = 0.121) or abdominal pain (6.85 ± 2.61 vs 5.00 ± 1.04, P = 0.380). The frequency of prolonged CTT was not significantly different between RH and non-RH groups (54.1% vs 58.3%, P = 0.403). RH patients rated more occurrence of FDD (72.1% vs 53.1%, P = 0.014) and dysynergic defecation (79.8% vs 50.2%, P = 0.004) than non-RH patients, whereas no differences were seen for inadequate defecatory propulsion (59.2% vs 55.0%, P = 0.589). After BFT, the proportion of "no effect" was significantly higher in the RH group than in the non-RH group (22.4% vs 9.4%, P = 0.010).RH is associated with obstructive defecation symptoms and the occurrence of FDD. Further studies are needed to detect the mechanism of RH's effect on BFT and FC.

Heavy metal and trace element concentrations in blood and follicular fluid affect ART outcome.

PubMed

Tolunay, Harun Egemen; Şükür, Yavuz Emre; Ozkavukcu, Sinan; Seval, Mehmet Murat; Ateş, Can; Türksoy, Vugar Ali; Ecemiş, Tolga; Atabekoğlu, Cem Somer; Özmen, Batuhan; Berker, Bülent; Sönmezer, Murat

2016-03-01

To assess the effects of heavy metal and trace element concentrations in blood and follicular fluid on assisted reproductive technology cycle outcome. A prospective study was conducted between January 2012 and July 2012 in a university hospital infertility clinic. One hundred and one patients with unexplained infertility who underwent intracytoplasmic sperm injection using GnRH-antagonist protocol were recruited. Concentrations of four toxic metals (Cd, Pb, Hg, As) and three trace elements (Cu, Zn, Fe) were measured both in blood and follicular fluid specimens. Patients were evaluated in two groups; the study group consisted of patients with ongoing pregnancy (n=20) and the reference group consisted of patients experienced assisted reproductive technology failure, miscarriage or biochemical pregnancy (n=81). Demographics and cycle parameters were comparable between the groups except for median number of day 3 Grade A embryos. Statistically significant negative correlations were found between blood Pb levels and number of MII oocytes, implantation, clinical pregnancy and ongoing pregnancy rates. Results of the log binomial regression revealed 2.2% lower risk for ongoing pregnancy for each 1μg/dL higher blood Pb concentration while holding the other variables in the model constant (RR 0.978; 95% CI 0.956-0.998; P=.041). Also, the results revealed 71.9% lower risk for ongoing pregnancy for each 1μg/dL higher follicular fluid Cu concentration while holding the other variables in the model constant (RR 0.288; 95% CI 0.085-0.92; P=.039). Blood concentrations of Pb and follicular fluid concentrations of Cu seem to have significant impacts on assisted reproductive technology cycle outcome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?

PubMed

Orvieto, R; Rabinson, J; Meltzer, S; Homburg, R; Anteby, E; Zohav, E

2006-01-01

The aim of the study was to evaluate the influence of type of GnRH-analog used during controlled ovarian hyperstimulation (COH) on the outcome of in vitro fertilization (IVF) cycles. All consecutive women aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004 were enrolled in the study. Only patients undergoing up to their third IVF cycle attempt were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred, and clinical pregnancy rate were compared between women given GnRH-agonist or GnRH-antagonist during COH. Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the agonist group and 261 in the antagonist group. A clinical pregnancy was achieved in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66 patients in the antagonist grup (pregnancy rate 25.3%); this difference was statistically significant (p < 0.01). The agonist group also used significantly more gonadotropin ampoules, required longer stimulation, and had higher estradiol levels on the day of human chorionic gonadotropin administration. The midluteal long GhRH-agonist suppressive protocol should be the protocol of choice in young patients in their first three IVF cycle attempts.

Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanikawa, S.; Nose, M.; Aoki, Y.

1990-08-01

We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony-forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF frommore » day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays.« less

Two years of replacement therapy in adults with growth hormone deficiency.

PubMed

Verhelst, J; Abs, R; Vandeweghe, M; Mockel, J; Legros, J J; Copinschi, G; Mahler, C; Velkeniers, B; Vanhaelst, L; Van Aelst, A; De Rijdt, D; Stevenaert, A; Beckers, A

1997-10-01

Although several studies have shown beneficial short-term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated. 148 adult GHD patients were enrolled in a multicentre 2-year rhGH replacement study which was placebo controlled for the first six months. rhGH (Genotropin/Genotonorm Pharmacia & Upjohn) was given in a dose of 0.25 IU/kg/week sc (1.5 IU/m2/day). Every 3-6 months body composition was measured using body impedance analysis and general well being was assessed using the Nottingham Health Profile (NHP) and social self-reporting questionnaire. At the same time patients had a full clinical examination and blood was sampled for glucose, HbA1c, IGF-1, creatinine, full blood count, thyroid hormones and liver function tests. With rhGH therapy IGF-1 levels increased from -2.00 +/- 2.60 SDS to 1.47 +/- 2.6 SDS after six months (P < 0.001), continued to rise despite no change in dose to 1.84 +/- 2.8 SDS after one year and remained constant thereafter (1.98 +/- 2.4 after 2 years). 56% of patients ultimately attained supranormal IGF-1 levels (+2 SD), 22% had levels below the mean, of which 9% were below -2 SD. Within 3 months lean body mass (LBM) increased by +5.09% (P < 0.001), total body water (TBW) by +5.40% (P < 0.001), while body fat (BF) dropped by -10.89% (P < 0.001) and waist circumference by -1.42% (P < 0.004). These effects were maintained during the first year of therapy, but the effect was attenuated after 24 months: LBM, +3.91% (P < 0.001); TBW, +3.28%, P < 0.001, BF, -6.42% (P < 0.001) and waist -2.22% (P < 0.009). Individual differences in response were large and could not be predicted by any of the baseline parameters, except for a better response in males. Treatment resulted in a large and progressive improvement on the NHP scale, especially energy, emotions and sleep, but a similar change was also found in patients during placebo treatment. With rhGH the number of full days of sick leave/6 months decreased from 12.17 +/- 3.90 days (SEM) to 7.15 +/- 3.50 days after six months (P = 0.009), 2.93 +/- 1.55 days after 12 months (P = 0.01), 0.39 +/- 0.17 days after 18 months (P < 0.001) and 3.3 +/- 2.51 days after 24 months (P = 0.026). Similarly, the hospitalization rate went down from 14.9 to 7% after 6 months and remained at this level thereafter (P = 0.12). About one third of patients on rhGH experienced fluid-related adverse events, most often within the first 3 months. They usually disappeared spontaneously or responded well to dose reduction. Cumulative dropout rates were 29% after 1 year and 38% after two years. Two thirds of these patients stopped treatment because of insufficient subjective improvement. Neither drop-outs nor fluid retention could not be predicted by any of the baseline parameters. We confirmed in a large group of patients the beneficial effects of rhGH therapy on body composition, metabolic parameters and general well-being and found a consistent drop in number of sick days and hospitalization rate. These effects were maintained during two years of therapy, except for an attenuation in body composition changes after 24 months. The high incidence of fluid-related adverse events suggests that it may be better to start with lower doses of rhGH and to increase the dose more slowly over a number of weeks. The finding of suboptimal high or low IGF-1 levels in many patients reinforces guidelines not to give rhGH in a weight-dependent dose but to titrate it individually for each patient.

Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH+LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome.

PubMed

Dubourdieu, Sophie; Fréour, Thomas; Dessolle, Lionel; Barrière, Paul

2013-05-01

To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Sang-wook; Jung, Kwon Il; Kim, Yeun Wha B.S.

2007-03-15

Purpose: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. Methods and Materials: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 {+-} 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 {mu}g/mL (Group 3), or 100 {mu}g/mLmore » (Group 4) rhEGF three times per day. Results: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 {mu}g/mL or 100 {mu}g/mL rhEGF. Conclusion: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats.« less

Bioactive nitric oxide concentration does not increase during reactive hyperemia in human skin.

PubMed

Zhao, J L; Pergola, P E; Roman, L J; Kellogg, D L

2004-02-01

This study examined whether nitric oxide (NO) is involved in the cutaneous response to reactive hyperemia (RH) in the human forearm. We enrolled seven healthy volunteers. NO concentrations were monitored using a NO selective amperometric electrode (ISO-NOP200, World Precision Instruments) inserted into the skin of the forearm. Laser-Doppler flowmetry (Moor Instruments) was used for monitoring skin blood flow (SkBF) at the same site. SkBF and NO levels were monitored and recorded continuously throughout the experiment. An intradermal microdialysis probe was inserted adjacent to the NO electrode for drug delivery. Data collection began 140 min after the NO electrodes and microdialysis probes were inserted. RH was achieved by the inflation of a blood pressure cuff to 25 mmHg above systolic pressure for 7 min after which the pressure in the cuff was abruptly released. Acetylcholine (ACh) was given by microdialysis probe at the end of RH study to verify the ability of the electrode system to detect changes in the NO concentration. SkBF and NO data before RH and immediately, 2, 5, 7, and 10 min after cuff deflation were used for analysis. SkBF increased immediately after release of the occlusion (P < 0.0001) and remained elevated for 2 min. No significant NO changes occurred with the increases in LDF. ACh induced increases in both SkBF and NO (P < 0.000 and P < 0.037, respectively). We conclude that RH increases SkBF by mechanisms that do not require a measurable increase in NO concentrations.

A model-based 'varimax' sampling strategy for a heterogeneous population.

PubMed

Akram, Nuzhat A; Farooqi, Shakeel R

2014-01-01

Sampling strategies are planned to enhance the homogeneity of a sample, hence to minimize confounding errors. A sampling strategy was developed to minimize the variation within population groups. Karachi, the largest urban agglomeration in Pakistan, was used as a model population. Blood groups ABO and Rh factor were determined for 3000 unrelated individuals selected through simple random sampling. Among them five population groups, namely Balochi, Muhajir, Pathan, Punjabi and Sindhi, based on paternal ethnicity were identified. An index was designed to measure the proportion of admixture at parental and grandparental levels. Population models based on index score were proposed. For validation, 175 individuals selected through stratified random sampling were genotyped for the three STR loci CSF1PO, TPOX and TH01. ANOVA showed significant differences across the population groups for blood groups and STR loci distribution. Gene diversity was higher across the sub-population model than in the agglomerated population. At parental level gene diversities are significantly higher across No admixture models than Admixture models. At grandparental level the difference was not significant. A sub-population model with no admixture at parental level was justified for sampling the heterogeneous population of Karachi.

Comparison of lenograstim vs filgrastim administration following chemotherapy for peripheral blood stem cell (PBSC) collection: a retrospective study of 126 patients.

PubMed

Lefrère, F; Bernard, M; Audat, F; Cavazzana-Calvo, M; Belanger, C; Hermine, O; Arnulf, B; Buzyn, A; Varet, B

1999-11-01

Mobilization techniques for peripheral blood stem cell (PBSC) collection include the administration of chemotherapy followed by hematopoietic growth factors or growth factors alone. Two forms of recombinant human granulocyte colony-stimulating factor (rhG-CSF) are available for PBSC mobilization: lenograstim and filgrastim which are the glycosylated and non-glycosylated forms respectively. In order to determine the influence of the two forms of G-CSF following chemotherapy on PBSC collection, we conducted a retrospective study in 126 patients with various hematological malignancies: 65 and 61 for the lenograstim and filgrastim groups respectively. No significant differences between the two groups were observed in terms of sex, age and diagnosis. Prior therapies and PBSC mobilization regimen were also equivalent. No significant difference was observed between the groups for the median CD34+ cells harvested. The number of leukapheresis necessary to obtain a minimal number of 3 x 10(6) CD34+ cells/kg was equivalent for the two groups. The proportion of patients affected by a failure in PBSC collection was similar in the two groups. Our data suggest that lenograstim and filgrastim are equivalent for PBSC mobilization after chemotherapy.

Assessment of ovarian reserve following ovarian tissue banking and/or GnRH-a co-treatment prior to chemotherapy in patients with Hodgkin's disease.

PubMed

Azem, Foad; Samara, Nivin; Cohen, Tanya; Ben-Yosef, Dalit; Almog, Beni; Lessing, Joseph B; Goor, Odeliya; Amit, Ami

2008-01-01

To examine ovarian reserve following chemotherapy in women with Hodgkin's disease. The study included nine patients who underwent ovarian tissue cryopreservation (OTCP) prior to chemotherapy consisting of the ABVD regimen (Adriamycin, bleomycin, vinblastine, and dacarbazine) and co-treatment with gonadotropin-releasing hormone agonist (GnRH-a) (Group A), and 13 patients treated by the ABVD protocol only without GnRH-a (Group B). The average age was 25.2 +/- 2.7 years for the women in Group A and 31.8 +/- 6.8 years for those in Group B. Six months following the end of chemotherapy, the menstrual cycle resumed in all Group A patients and in four Group B patients who had amenorrhea. Eight Group B patients had regular menses during and after chemotherapy. None of the patients suffered from ovarian failure. Two Group A patients conceived in the first year after completing chemotherapy. Co-treatment with GnRH-a has little effect on ovarian protection in women with Hodgkin's disease.

Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants.

PubMed

Sykaras, N; Triplett, R G; Nunn, M E; Iacopino, A M; Opperman, L A

2001-08-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in bony defects created within the hollow chamber of endosseous dental implants in 14 foxhound dogs. Bilateral extractions of mandibular premolars were performed and surgical implantation of 104 hollow cylinder implants followed after 8 weeks of healing. Experimental implants had their hollow chamber filled with 20 microg of rhBMP-2 delivered with a bovine collagen carrier, whereas the control implants had their apical chamber left empty. Dogs were followed for 2, 4, 8 and 12 weeks. Histomorphometric evaluation and immunohistochemical analysis were performed. Minimal bone was regenerated at 2 weeks for both groups. At 4 weeks, bone fill averaged 23.48% for the rhBMP-2 and 5.98% for the control group (P<0.05). At 8 weeks, mean bone fill was 20.94% and 7.75% for the rhBMP-2 and the controls, respectively (P<0.05). At 12 weeks, mean bone fill was 31.39% and 24.31% for the rhBMP-2 and control implants, respectively (P>0.05). Bone-implant contact (BIC) increased for both groups over time and at 8 weeks the rhBMP-2 BIC value was 18.65% and for the control 7.22% (P<0.05). At 12 weeks, the BIC was 43.78% and 21.05% for the rhBMP-2 and the control group, respectively (P<0.05). Immunohistochemical staining for type II collagen was positive only for parts of the collagen carrier and formation of cartilaginous intermediate was not observed in any of the specimens. The results suggest that, in confined defects adjacent to dental implants, rhBMP-2 can induce bone regeneration in close apposition to the implant surface.

Physiological responses to changes in relative humidity under thermally neutral, warm and hot conditions.

PubMed

Kakitsuba, Naoshi

2016-07-01

Four hypothetical thermophysiological responses to changes in relative humidity (Rh) under thermally neutral, warm, and hot conditions were proposed for a person at rest. Under thermally neutral and warm conditions, the first hypothetical response to an increase in Rh was a decrease in mean skin temperature (T¯sk) due to increase in mean evaporation rate (E¯sk), and the second hypothetical response to a decrease in Rh was a decrease, an increase, or no change in T¯sk, depending on changes in the E¯sk. Under hot conditions, the third hypothetical response to an increase in the Rh was an increase in T¯sk or decrease in T¯sk upon decrease in the Rh due to changes in E¯sk, and the forth hypothetical response to an increase in Rh was an increase in T¯sk due to increase in the peripheral blood flow rate (SkBF). To test these hypotheses, the T¯sk and E¯sk of four young male volunteers were measured at 28°C, 30°C, or 32°C while the Rh was maintained at 40% or 80% Rh for 60min after 20min exposure at 60% Rh (control condition). In a second experiment, the T¯sk, E¯sk, and SkBF of five young male volunteers were measured at 34°C-40% Rh or 36°C-40% Rh, or 34°C-70% Rh or 36°C-70% Rh for 60min after 20min exposure at 28°C-60% Rh (control condition). The first hypothesis was partly supported by the findings that the T¯sk was lower than the control values at 28°C-80% Rh and the E¯sk was higher than the control values at 80% Rh at any tested temperature. The second hypothesis was partly supported by the findings that the T¯sk was lower than the control values at 28°C-40% Rh, and there were small changes in both T¯sk and E¯sk at 30°C-40% Rh. The third and fourth hypotheses were supported by the findings that the T¯sk at 36°C-70% Rh was significantly higher (p<0.01) than at 36°C-40% Rh, the E¯sk was significantly higher (p<0.01) at 70% Rh than at 40% Rh, and SkBF was positively correlated with T¯sk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of different hormonal combinations on follicular wave emergence and superovulatory response in sheep.

PubMed

Souza-Fabjan, Joanna Maria Gonçalves; da Rosa, Rômulo Mendonça; Balaro, Mário Felipe Alvarez; Pinto, Pedro Henrique Nicolau; Dos Santos, Gustavo Bervian; Arashiro, Eduardo Kenji Nunes; da Fonseca, Jeferson Ferreira; Ungerfeld, Rodolfo; Brandão, Felipe Zandonadi

2017-11-01

The aim of the present study was to compare hormonal treatments to induce and synchronize follicular wave emergence to improve the results of superovulatory (SOV) treatments in ewes. In Experiment 1 (n = 66), ewes were treated with a progesterone intravaginal implant plus a PGF 2α analogue (group G P4 ), or with the same treatment plus estradiol benzoate (G P4+EB ), a GnRH agonist (G P4+GnRH ), or both, estradiol benzoate and a GnRH agonist (G P4+EB+GnRH ) in a 2 × 2 factorial arrangement. Follicular wave emergence was determined by ultrasound. Follicular wave did not emerge during the studied period in 10 females (one from G P4 , six from G P4+EB and three from G P4+EB+GnRH ). Follicular emergence was less synchronized (P = 0.007) when estradiol was administered (G P4+EB : 103.6 ± 22.0 h), without any interaction with GnRH treatment (G P4+EB+GnRH : 80.1 ± 21.4 h, G P4+GnRH : 52.5 ± 8.7 h, G P4 : 56.6 ± 10.4 h). Estradiol administration delayed the moment of follicular emergence (P = 0.007) and the follicular wave emergence moment in which follicular dominance was achieved (P = 0.009), without interactions between estradiol and GnRH in the moment of follicular wave emergence or dominance. In Experiment 2 (n = 22), two SOV protocols were compared: the best treatment of Experiment 1 (G P4 ) was used to synchronize follicular wave emergence, initiating the SOV treatment 2.5 days later; in the control treatment, SOV treatment started 80 h after a short-term protocol to synchronize ovulation (G control ). The number of corpora lutea (CL) and the evaluation of the collected embryos were performed six days after estrus. Blood samples were collected daily for plasma progesterone determination. Although the number of CL was similar in G control (7.1 ± 1.0) and G P4 (6.9 ± 5.1), the number of structures and viable embryos recovered were greater in G control (P < 0.05). The occurrence of luteal premature regression was significantly greater in G P4 (60%) than in G control (8.3%). The use of GnRH agonist alone did not improve synchronization of follicular wave emergence. When EB was used (alone or associated) follicular wave emergence was less synchronized. The SOV protocol proposed had a similar ovarian response; however, it resulted in less transferable embryos. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of recombinant human follicle-stimulating hormone and luteinizing hormone on in vitro maturation of porcine oocytes evaluated by the subsequent in vitro development of embryos obtained by in vitro fertilization, intracytoplasmic sperm injection, or parthenogenetic activation.

PubMed

Silvestre, M A; Alfonso, J; García-Mengual, E; Salvador, I; Duque, C C; Molina, I

2007-05-01

The aim of this work was to study the effect of recombinant human (rh) FSH and LH on in vitro maturation of pig oocytes compared with a conventional hormonal supplement based on equine (PMSG) and human chorionic gonadotropins (hCG), as evaluated by the developmental ability of 3 types of pig embryos obtained by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or artificial activation (ATA). In Exp. 1, one cumulus-oocyte complex group (A group) was supplemented with rh-FSH and rh-LH (0.1 IU/mL each), and the other group (B group) was supplemented with PMSG and hCG (10 IU/mL each). No differences in nuclear maturation between the A and B groups were observed (68.5 vs. 71.4%, respectively). No differences were detected between hormonal treatments in the rates of cleavage or blastocyst formation of ATA, IVF, and ICSI embryos. Total cell number of the embryos was not significantly different in any experimental group (A: 31.1, 28.5, and 19.8 vs. B: 25.2, 25.5, and 20.6 for ATA, IVF, and ICSI embryos, respectively). In Exp. 2, the effects of different concentrations of rh-FSH and rh-LH (0.5, 0.1, or 0.05 IU/mL) in maturation medium on nuclear maturation and in vitro development of embryos obtained by IVF were studied. No effect of different hormonal concentrations on blastocyst formation rates was observed (8.5, 13.0, and 5.7%, respectively). Blastocyst cell number was not different in any experimental group. In conclusion, the results obtained here permit us to substitute PMSG and hCG with rh-FSH and rh-LH and to produce pig embryos obtained by IVF, ICSI, or ATA.

Radiographic Appearance of Transforaminal Lumbar Interbody Fusion Performed With and Without Recombinant Human Morphogenetic Protein-2.

PubMed

Stensby, J Derek; Kaliney, Ryan W; Alford, Bennett; Shen, Francis H; Patrie, James T; Fox, Michael G

2016-03-01

The purpose of this study is to determine whether recombinant human morphogenetic protein-2 (rhBMP-2) alters the findings on routine radiographs performed after transforaminal lumbar interbody fusion (TLIF). A retrospective review of 256 TLIF procedures in 200 patients was performed over a 4-year period. The rhBMP-2 group included 204 TLIFs in 160 patients, and the control group included 52 TLIFs in 40 patients. Two musculoskeletal radiologists reviewed the postoperative radiographs for endplate resorption, resorption resolution, new bone formation, bridging bone, and allograft migration. Statistical analysis was performed using logistic regression. The median age was 53 years in the rhBMP-2 group and 54 years in the control group (p = 0.182). The groups were similar with regard to sex (p = 0.517), single or multilevel TLIF (p = 0.921), specific TLIF levels (p = 0.53), and median radiographic follow-up (373 vs 366 days; p = 0.34). Findings that were more common in the rhBMP-2 group than in the control group included endplate resorption (38% [78/204] vs 12% [6/52]; odds ratio [OR], 4.67; 95% CI, 1.99-12.54; p < 0.001), resorption resolution (59% [46/78] vs 0% [0/6]; OR, 8.09; 95% CI, 1.41 to ∞; p = 0.022), new bone formation (84% [171/204] vs 67% [35/52]; OR, 2.51; 95% CI, 1.24-4.99; p = 0.011), bridging bone (55% [112/204] vs 31% [16/52]; OR, 2.73; 95% CI, 1.43-5.34; p = 0.002), and allograft migration (17% [35/204] vs 2% [1/52]; OR, 6.30; 95% CI, 0.91-151.41; p = 0.065). A statistically significant higher frequency of endplate resorption, new bone formation, and bone bridging is present in TLIF augmented by rhBMP-2 compared with TLIF performed without rhBMP-2. Endplate resorption resolves without treatment in most cases after rhBMP-2 use.

Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With Hypogonadotropic Hypogonadodism.

PubMed

Gong, Chunxiu; Liu, Ying; Qin, Miao; Wu, Di; Wang, Xiaoling

2015-07-01

We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups. Boys with HH may be effectively treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating adolescent boys with HH than hCG.

A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle.

PubMed

Haydardedeoğlu, Bülent; Kılıçdağ, Esra Bulgan

2016-01-01

Corifollitropin alfa is a good choice for assisted reproductive technology (ART) cycles because fewer injections are needed than with other agents. In this retrospective cohort, we analyzed luteal injected half-dose depot gonadotropin hormone-releasing hormone (GnRH) agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist. In this retrospective cohort, we analyzed luteal injected half-dose depot GnRH agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist at the Division of Reproductive Endocrinology and IVF Unit, Obstetrics and Gynecology Department, Başkent University School of Medicine, Adana, Turkey, from March 2014 to August 2015. The patient's baseline characteristics were similar between the two groups. Forty-five patients underwent the long protocol, in which a half-dose of depot GnRH agonist was administered on day 21 of the preceding cycle. Forty-nine patients underwent the GnRH-antagonist protocol. Corifollitropin alfa was administered on the menstrual cycle day 3. The mean ages of the two groups were similar (32.77±5.55 vs. 34.2±4.51 years ["for the long- and antagonist-protocol groups, respectively"]). The total number of retrieved oocytes, the fertilization rate, and the number of transferred embryos were similar between the two groups. The only significant difference between the two protocols was the number of injections during the controlled ovarian stimulation (COH) cycle, which included the depot-agonist injection in the long-protocol group (4.46±1.64 vs. 5.71±2.51, p=0.006). The clinical pregnancy and implantation rates were similar in the two protocols (16/45 [35.6%] vs. 16/49 [32.7%] for the intention to treat and 32.5±6.82% vs. 36.25±8.58%, respectively). Our results show that ART cycles could be performed with fewer injections using corifollitropin alfa and a half-dose of depot GnRH agonist.

Comparative study of hematological responses to platinum group metals, antimony and silver nanoparticles in animal models.

PubMed

Newkirk, Catherine E; Gagnon, Zofia E; Pavel Sizemore, Ioana E

2014-01-01

Research was conducted to examine the hematological effects of heavy metals (platinum (Pt ((IV))), palladium (Pd ((II))), rhodium (Rh ((III))), antimony (Sb ((III)) and Sb ((V))), and silver nanoparticles (AgNPs)) on white blood cells in mammalian (rat) and avian (chick embryo) models. These metals are used in many everyday products and are accumulating in our environment. Six-week old Sprague-Dawley female rats were treated daily by gavage and six-day old, fertile, specific pathogen-free white leghorn strain chick embryos' eggs were injected on days 7 and 14 of incubation with 0.0, 1.0, 5.0 or 10.0 ppm concentrations of Pt ((IV)) and a platinum group metal (PGM) mix of Pt ((IV)), Pd ((II)) and Rh ((III)). Chick embryos were also tested with 1.0 or 5.0 ppm of antimony compounds (Sb ((III)) and Sb ((V))) and 0.0, 15.0, 30.0, 60.0, or 100.0 ppm of silver nanoparticles (AgNPs). After 8 weeks of treatment, blood was obtained from the rats by jugular cut down and from chick embryos on day 20 of incubation by heart puncture. Blood smears were made and stained and a differential white cell count was performed on each. Examination of the smears revealed unconventional dose responses, stimulation of the immune response, and decreases in leukocyte production with various metals and concentrations. Chick embryos responded differently than rats to Pt and the PGM mix; suggesting that species differences and/or stage of development are important components of response to heavy metals. Route of administration of the metals might also influence the response. All of the heavy metals tested affected the immune responses of the tested animals as demonstrated by changes in the types and numbers of leukocytes. Our findings warrant further research to determine the mechanism of these effects and to understand and prevent toxicological effects in humans and other living organisms.

Relationship between skin blood flow and sweating rate, and age related regional differences.

PubMed

Inoue, Y; Shibasaki, M; Hirata, K; Araki, T

1998-12-01

To examine the mechanisms and regional differences in the age-related decrement of skin blood flow, 11 young (age 20-25 years) and 10 older (age 64-76 years) men were exposed to a mild heat stress by immersing their feet and lower legs in water at 42 degrees C for 60 min, while they were sitting in near thermoneutral conditions [25 degrees C and 45% relative humidity (rh)]. During the equilibrium period (25 degrees C and 45% rh) before the heat test, no group differences were observed in rectal (Tre) and mean skin (Tsk) temperatures or mean arterial pressure (MAP). During passive heating, Tsk was significantly lower in the older men 20 min after commencing exposure (P<0.001), although there were similar increases in Tre in both groups. Exposure time and age did not affect MAP. The local sweating rate (m(sw)) and the percentage change in skin blood flow by laser Doppler flowmetry (%LDF) relative to baseline values on the chest, back, forearm and thigh were significantly lower in the older men (P<0.001), especially on the thigh. After starting the heat exposure, three temporal phases were observed in the relationship between %LDF and m(sw) at most sites in each subject. In phase A, %LDF increased but with no increase in m(sw). In phase B, m(sw) increased but with no secondary increase in %LDF. Finally, in phase C, there were proportional increases in %LDF and m(sw). The increase in %LDF in phase A was significantly lower on the forearm and thigh (P<0.05) for the older men, but not on the chest and back. In phase C, the slopes of the regression lines between %LDF and m(sw) were lower for the older men on the back (P<0.03), forearm (P = 0.08) and thigh (P<0.03), but not on the chest. These results would suggest that the age-related decrement in skin blood flow in response to passive heating may be due in part to a smaller release of vasoconstrictor tone and to less active vasodilatation once sweating begins. Regional differences exist in the impaired vasoconstriction and active vasodilatation systems.

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

PubMed

Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Satıroğlu, Hakan

2010-01-01

To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.

Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols.

PubMed

Toftager, Mette; Sylvest, Randi; Schmidt, Lone; Bogstad, Jeanette; Løssl, Kristine; Prætorius, Lisbeth; Zedeler, Anne; Bryndorf, Thue; Pinborg, Anja

2018-01-01

To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH antagonist or long GnRH agonist protocol. Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing. Fertility clinics at university hospitals. Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols. Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495 women allocated to a long GnRH agonist protocol. Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment. Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically. Women in a short GnRH antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly. NCT00756028. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2).

PubMed

Kenley, R; Marden, L; Turek, T; Jin, L; Ron, E; Hollinger, J O

1994-10-01

In the current investigation, we report osseous regeneration in critical-size rat calvarial defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) and novel delivery systems based on biomaterials. The novel systems combine rhBMP-2 with dry powder microparticles of poly(D,L-lactide-co-glycolide) (PLGA). The mixture of rhBMP-2 with PLGA microparticles is added to an aqueous solution of biopolymer to yield a semisolid paste. The biopolymers tested include autologous blood clot, hydroxypropyl methylcellulose, and sodium alginate cross-linked with calcium ion. Insoluble collageneous bone matrix was also studied as a control. Test articles were made at 0-, 10-, and 30-micrograms doses of rhBMP-2 and imiplanted in 8-mm-diameter rat calvarial defects (which will not heal if left untreated). The animals were examined 21 days after implantation by radiography, radiomorphometry, histology, and histomorphometry. All tested materials containing rhBMP-2 restored radiopacity and normal contouring to the calvarial defects. Samples without added rhBMP-2 yielded only soft tissue within the defects. Histology showed restoration of inner and outer bone tables plus marrow constituents. The PLGA microparticles were significantly resorbed at the 21-day time point. Although small differences between delivery systems were evident at 0- and 10-micrograms rhBMP-2 doses, all test articles performed essentially equivalently at the 30-micrograms dose. Thus, novel delivery systems for rhBMP-2 offer the promise of combining the intrinsic bioactivity of the osteoinductive protein with pharmaceutically acceptable biomaterials.

The effect of recombinant GM-CSF on the recovery of monkeys transplanted with autologous bone marrow.

PubMed

Monroy, R L; Skelly, R R; MacVittie, T J; Davis, T A; Sauber, J J; Clark, S C; Donahue, R E

1987-11-01

The regulatory function of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte production in vivo was evaluated in an autologous bone marrow transplantation model using rhesus monkeys. Monkeys were exposed to 9.0 Gy total body irradiation and then transplanted with 5.0 x 10(7) low-density bone marrow cells/kg. Alzet miniosmotic pumps were subcutaneously implanted to deliver rhGM-CSF at a rate of 50,400 U/kg/d. Minipumps, containing either rhGM-CSF or saline, were implanted between zero and five days after transplantation for seven days. Kinetic recoveries of peripheral blood cells after either saline or rhGM-CSF treatment were compared. Treatment with rhGM-CSF accelerated the recovery of neutrophils. Neutrophils in rhGM-CSF-treated animals recovered to 80% (3.4 x 10(3)/mm3) pre-irradiation control levels by day 20, in comparison with only 33% (0.9 x 10(3)/mm3) recovery for saline control monkeys. In addition, the recovery of neutrophils was enhanced over that of the controls, reaching 140% v 70% on day 30. Another prominent feature of rhGM-CSF-treated monkeys was the accelerated recovery of platelets, reaching near 50% normal levels by day 24 in comparison with 20% of normal levels for controls. The infusion of rhGM-CSF was shown to be an effective regulator of early hematopoietic regeneration, leading to the accelerated recovery of both neutrophils and platelets and then providing a consistent sustained increase of neutrophils even in the absence of rhGM-CSF.

Green light inhibits GnRH-I expression by stimulating the melatonin-GnIH pathway in the chick brain.

PubMed

Zhang, L; Chen, F; Cao, J; Dong, Y; Wang, Z; Hu, M; Chen, Y

2017-05-01

To study the mechanism by which monochromatic light affects gonadotrophin-releasing hormone (GnRH) expression in chicken hypothalamus, a total of 192 newly-hatched chicks were divided into intact, sham-operated and pinealectomy groups and exposed to white (WL), red (RL), green (GL) and blue (BL) lights using a light-emitting diode system for 2 weeks. In the GL intact group, the mRNA and protein levels of GnRH-I in the hypothalamus, the mean cell area and mean cell optical density (OD) of GnRH-I-immunoreactive (-ir) cells of the nucleus commissurae pallii were decreased by 13.2%-34.5%, 5.7%-39.1% and 9.9%-17.3% compared to those in the chicks exposed to the WL, RL and BL, respectively. GL decreased these factors related to GnRH-I expression and the effect of GL was not observed in pinealectomised birds. However, the mRNA and protein levels of hypothalamic gonadotrophin-inhibitory hormone (GnIH) and GnIH receptor (GnIHR), the mean cell area and mean cell OD of the GnIH-ir cells of the paraventricularis magnocellularis, and the plasma melatonin concentration in the chicks exposed to GL were increased by 18.6%-49.2%, 21.1%-60.0% and 8.6%-30.6% compared to the WL, RL and BL intact groups, respectively. The plasma melatonin concentration showed a negative correlation with GnRH-I protein and a positive correlation with GnIH and GnIHR proteins. Protein expression of both GnRH-I and GnIHR showed a negative correlation in the hypothalamus. After pinealectomy, GnRH-I expression increased, whereas plasma melatonin concentration, GnIH and GnIHR expression decreased, and there were no significant differences among the WL, RL, GL and BL groups. Double-labelled immunofluorescence showed that GnIH axon terminals were near GnRH-I neurones, some GnRH-I neurones coexpressed with GnIHR and GnIH neurones coexpressed with melatonin receptor subtype quinone reductase 2. These results demonstrate that green light inhibits GnRH-I expression by increasing melatonin secretion and stimulating melatonin receptor-GnIH-GnIH receptor pathway in the chick brain. © 2017 British Society for Neuroendocrinology.

Rh Factor Blood Test

MedlinePlus

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Gonadotropin-releasing hormone agonist triggering with concomitant administration of low doses of human chorionic gonadotropin or a freeze-all strategy in high responders.

PubMed

Karacan, Meric; Erdem, Erkan; Usta, Akin; Arvas, Ayse; Cebi, Ziya; Camlibel, Teksen

2017-06-01

To compare the live birth rates and moderate/severe ovarian hyperstimulation syndrome (OHSS) rates of 2 different approaches using gonadotropin-releasing hormone (GnRH) agonist triggering in high responder women. Methods: A retrospective cohort study was performed to evaluate intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) outcomes in high responder women who underwent ovulation induction with a GnRH antagonist protocol between April 2011 and March 2015. In group 1 (n=74), GnRH agonist was used for ovulation triggering with the concomitant use of 1500 IU of urinary human chorionic gonadotropin (hCG) immediately after oocyte retrieval followed by fresh ET and standard luteal support. In group 2 (n=48), GnRH agonist was used for triggering after freezing all embryos and subsequent frozen/thawed embryo transfer (FET); this approach is considered the "freeze-all" approach. Results: Baseline characteristics were similar between the groups. The clinical pregnancy rates for group 1 was 45.9% and group 2 was 43.8% (p=0.812, chi-squared test) and live birth rates for group 1 was 40.5% and for group 2 41.7% (p=0.902, chi-squared test) were comparable between groups. In group 1, late-onset OHSS was observed (one severe case and one moderate case) in 2 patients (2.7%). In group 2, none of the patients experienced moderate/severe OHSS. Conclusion: The live birth rate with GnRH agonist triggering and concomitant use of 1500 IU of hCG immediately after oocyte retrieval was similar to that obtained with the freeze-all approach and FET in a subsequent cycle. The administration of a low dose of hCG in GnRH agonist trigger cycles caused moderate/severe OHSS in 2.7% of the patients.

A procedure for rapid issue of red cells for emergency use.

PubMed

Weiskopf, Richard B; Webb, Mary; Stangle, Deena; Klinbergs, Gunter; Toy, Pearl

2005-04-01

A College of American Pathologists Q-Probe revealed that the median turnaround times for emergency requests for red blood cells from the operating room were 30 minutes to release of cells from the blood bank and 34 minutes to delivery to the operating room. These times may not be adequate to permit the red cells to provide sufficiently rapid delivery of oxygen in massively bleeding patients. To improve the time from emergency request for red cells to delivery to the operating room. A new emergency issue program was implemented for only the operating rooms; emergency issue to all other hospital locations remained unchanged. Six units of group O Rh-negative red blood cells (RBCs) are maintained in the blood bank in a separate basket with transfusion forms containing the unit numbers and expiration dates and a bag with one blood tubing segment from each unit. The times to issue and to delivery to the operating room suite were compared with time to issue of 2 group O Rh-negative RBCs for other hospital locations using the older system during the same time period and with the time to issue of 2 units to all other hospital locations during the preceding 2 years. A university hospital. Time between emergency request for red cells and delivery to the operating room. The time between blood bank notification and arrival in the operating room of the 6 units of RBCs was significantly shorter than the time required to just issue (not including delivery time) 2 units of RBCs to other hospital locations. With the new procedure, 82% of units issued reached the operating room within 2 minutes of request, 91% arrived within 3 minutes, and 100% arrived within 4 minutes. These percentages are significantly higher than those for only issue of blood (without delivery) using the older issuing procedure for all hospital locations during the previous 2 years (37%, 49%, and 66%, respectively; P = .007, .009, and .02, respectively) and for other locations during the same 7-month period (29%, 46%, and 73%, respectively; P = .004, .01, and .09, respectively). Time (mean [95% confidence interval]) from blood bank notification to delivery of RBCs to the operating room suite (2.1 [1.6-2.6] minutes, of which approximately 50-60 seconds is attributable to delivery time) was less than issue times (not including delivery times) using the older issuing procedure for other hospital locations during the same period (4.1 [3.1-5.0] minutes; P = .007). An emergency issue procedure can be used to issue several units of RBCs within 1 minute and have them delivered to the operating room within 2 minutes while maintaining sufficient controls and providing required information to satisfy patient and blood bank requirements.

Repair of rotator cuff injuries using different composites.

PubMed

Lopiz, Y; Arvinius, C; García-Fernández, C; Rodriguez-Bobada, M C; González-López, P; Civantos, A; Marco, F

Rotator cuff repairs have shown a high level of re-ruptures. It is hypothesised that the use of rhBMP-2 in a carrier could improve the biomechanical and histological properties of the repair. Controlled experimental study conducted on 40 rats with section and repair of the supraspinatus tendon and randomisation to one of five groups: Group 1 (control) only suture; Group 2 (double control), suture and alginate-chitin carrier; Group 3 (alginate-control), the rhBMP-2 was added to the alginate; Group 4 (chitin-control) application of the rhBMP-2 to the chitin, and Group 5 (double sample): The two components of the carrier (alginate and chitin) have rhBMP-2. A biomechanical and histological analysis was performed at 4 weeks. A gap was observed in all cases 4 weeks after supraspinatus detachment. The re-rupture rate was 7.5%, with 20% of them in the control-alginate Group. Histologically the best results were obtained in the double sample group: 4.5 (3.3-5.0). Double sample were also able to support higher loads to failure: 62.9N (59.8 to 69.4) with lower rigidity 12.7 (9.7 to 15.9). The use of alginate-chitin carrier with rhBMP-2 improves the biomechanical and histological properties of the repair site in a chronic rotator cuff tear. Copyright © 2016 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Analysis of stem cell apheresis products using intermediate-dose filgrastim plus large volume apheresis for allogeneic transplantation.

PubMed

Engelhardt, M; Bertz, H; Wäsch, R; Finke, J

2001-04-01

Previously, a dose-dependent influence of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on CD34+ mobilization was demonstrated. In this single-center prospective analysis, 52 healthy donors were investigated to determine the efficacy of intermediate-dose rhG-CSF 2x8 microg/kg donor body weight (bw) and intermediate large volume apheresis (LVA, median 12 l) to mobilize peripheral blood progenitor cells (PBPC) for allogeneic transplantation. The median number of CD34+ cells in apheresis products was 0.45% and 2.2x10(6)/kg recipient bw per single apheresis. A total of 5.4x10(6)/kg CD34+ cells were collected with two (range: one to three) LVA. In the analysis of donor subgroups, higher peripheral blood (PB) and apheresis results were obtained in male vs female donors; however, donor weight significantly differed in both groups. Heavier donors displayed higher PB and apheresis CD34+ counts; however, when CD34+ cells/kg were adjusted to a constant bw, similar harvest results were calculated in males and females, demonstrating that gender per se does not, whereas bw does affect apheresis results. Younger donors had significantly higher PB CD34+ counts, higher CD34+ numbers per single apheresis, increased CFU, more T, B, and CD61+, comparable NK, and less CD14+ cells. A correlation analysis of donor age and apheresis results displayed an age-related decline of 0.46x10(6)/kg CD34 cells per decade of donor aging. Cell subsets in apheresis products were CD14 (49%), CD3 (22%), CD4 (13%), CD8 (7%), CD61 (20%), CD19 (5%), and CD16/56+ (3%) cells, with increasing CD14+ cells and decreasing CD3, CD4, CD8, CD61, CD19, and CD16/56+ cells on subsequent days of apheresis. Compared to our previous analysis using high- (2x12 microg) and low-dose (1x10 microg) rhG-CSF for allogeneic PBPC mobilization, the intermediate-dose showed a similar CD34+ mobilization potential to 1x10 microg rhG-CSF; however, with use of LVA, two instead of three (p<0.05) aphereses were sufficient to mobilize > or =4x10(6)/kg bw CD34+ cells in most donors. Taken together, our results demonstrate that intermediate-dose rhG-CSF sufficiently mobilizes > or =4x10(6)/kg x bw CD34+ cells with use of LVA and that especially younger donors display increased CD34+ cell numbers.

Prevalence and clinical characteristics of isolated-office and true resistant hypertension determined by ambulatory blood pressure monitoring.

PubMed

Ríos, María T; Domínguez-Sardiña, Manuel; Ayala, Diana E; Gomara, Sonia; Sineiro, Elvira; Pousa, Lorenzo; Callejas, Pedro A; Fontao, María J; Fernández, José R; Hermida, Ramón C

2013-03-01

Hypertension is defined as resistant to treatment when a therapeutic plan including ≥3 hypertension medications failed to sufficiently lower systolic (SBP) and diastolic (DBP) blood pressures (BPs). Most individuals, including those under hypertension therapy, show a "white-coat" effect that could cause an overestimation of their real BP. The prevalence and clinical characteristics of "white-coat" or isolated-office resistant hypertension (RH) has always been evaluated by comparing clinic BP values with either daytime home BP measurements or the awake BP mean obtained from ambulatory monitoring (ABPM), therefore including patients with either normal or elevated asleep BP mean. Here, we investigated the impact of including asleep BP mean as a requirement for the definition of hypertension on the prevalence, clinical characteristics, and estimated cardiovascular (CVD) risk of isolated-office RH. This cross-sectional study evaluated 3042 patients treated with ≥3 hypertension medications and evaluated by 48-h ABPM (1707 men/1335 women), 64.2 ± 11.6 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 522 (17.2%) had true isolated-office RH (elevated clinic BP and controlled awake and asleep ambulatory BPs while treated with 3 hypertension medications), 260 (8.6%) had false isolated-office RH (elevated clinic BP, controlled awake SBP/DBP means, but elevated asleep SBP or DBP mean while treated with 3 hypertension medications), and the remaining 2260 (74.3%) had true RH (elevated awake or asleep SBP/DBP means while treated with 3 medications, or any patient treated with ≥4 medications). Patients with false, relative to those with true, isolated-office RH had higher prevalence of microalbuminuria and chronic kidney disease (CKD), significantly higher albumin/creatinine ratio (p < .001), significantly higher 48-h SBP/DBP means by 9.6/5.3 mm Hg (p < .001), significantly lower sleep-time relative SBP and DBP decline (p < .001), and significantly greater prevalence of a non-dipper BP profile (96.9% vs. 38.9%; p < .001). Additionally, the prevalence of the riser BP pattern, which is associated with highest CVD risk, was much greater, 40.4% vs. 5.0% (p < .001), among patients with false isolated-office RH. The estimated hazard ratio of CVD events, using a fully adjusted model including the significant confounding variables of sex, age, diabetes, chronic kidney disease, asleep SBP mean, and sleep-time relative SBP decline, was significantly greater for patients with false compared with those with true isolated-office RH (2.13 [95% confidence interval: 1.95-2.32]; p < .001). Patients with false isolated-office hypertension and true RH, however, were equivalent for the prevalence of obstructive sleep apnea, metabolic syndrome, obesity, diabetes, microalbuminuria, and chronic kidney disease, and they had an equivalent estimated hazard ratio of CVD events (1.04 [95% confidence interval: .97-1.12]; p = .265). Our findings document a significantly elevated prevalence of a blunted nighttime BP decline in patients here categorized as either false isolated-office RH and true RH, jointly accounting for 82.8% of the studied sample. Previous reports of much lower prevalence of true RH plus a nonsignificant increased CVD risk of this condition compared with isolated-office RH are misleading by disregarding asleep BP mean for classification. Our results further indicate that classification of RH patients into categories of isolated-office RH, masked RH, and true RH cannot be based on the comparison of clinic BP with either daytime home BP measurements or awake BP mean from ABPM, as so far customary in the available literature, totally disregarding the highly significant prognostic value of nighttime BP. Accordingly, ABPM should be regarded as a clinical requirement for proper diagnosis of true RH.

Transfusion strategy for weak D type 4.0 based on RHD alleles and RH haplotypes in Tunisia

PubMed Central

Ouchari, Mouna; Srivastava, Kshitij; Romdhane, Houda; Yacoub, Saloua Jemni; Flegel, Willy Albert

2017-01-01

Background With more than 460 RHD alleles, this gene is the most complex and polymorphic among all blood group systems. The Tunisian population has the largest known prevalence of weak D type 4.0 alleles, occurring in 1 of 105 RH haplotypes. We aimed to establish a rationale for the transfusion strategy of weak D type 4.0 in Tunisia. Study design and methods Donors were randomly screened for the serological weak D phenotype. The RHD coding sequence and parts of the introns were sequenced. To establish the RH haplotype, the RHCE gene was tested for characteristic single nucleotide positions. Results We determined all RHD alleles and the RH haplotypes coding for the serologic weak D phenotype among 13,431 Tunisian donations. A serologic weak D phenotype was found in 67 individuals (0.50%). Among them, 60 carried a weak D type 4 allele: 53 weak D type 4.0, 6 weak D type 4.2.2 (DAR), and 1 weak D type 4.1. Another 4 donors had 1 variant allele each: DVII, weak D type 1, weak D type 3, and weak D type 100, while 3 donors showed a normal RHD sequence. The weak D type 4.0 was most often linked to RHCE*ceVS.04.01, weak D type 4.2.2 to RHCE*ceAR, and weak D type 4.1 to RHCE*ceVS.02, while the other RHD alleles were linked to one of the common RHCE alleles. Conclusions Among the weak D phenotypes in Tunisia, no novel RHD allele was found and almost 90% were caused by alleles of the weak D type 4 cluster, of which 88% represented the weak D type 4.0 allele. Based on established RH haplotypes for variant RHD and RHCE alleles and the lack of adverse clinical reports, we recommend D positive transfusions for patients with weak D type 4.0 in Tunisia. PMID:29193104

Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes in Tunisia.

PubMed

Ouchari, Mouna; Srivastava, Kshitij; Romdhane, Houda; Jemni Yacoub, Saloua; Flegel, Willy Albert

2018-02-01

With more than 460 RHD alleles, this gene is the most complex and polymorphic among all blood group systems. The Tunisian population has the largest known prevalence of weak D Type 4.0 alleles, occurring in one of 105 RH haplotypes. We aimed to establish a rationale for the transfusion strategy of weak D Type 4.0 in Tunisia. Donors were randomly screened for the serologic weak D phenotype. The RHD coding sequence and parts of the introns were sequenced. To establish the RH haplotype, the RHCE gene was tested for characteristic single-nucleotide positions. We determined all RHD alleles and the RH haplotypes coding for the serologic weak D phenotype among 13,431 Tunisian donations. A serologic weak D phenotype was found in 67 individuals (0.50%). Among them, 60 carried a weak D Type 4 allele: 53 weak D Type 4.0, six weak D Type 4.2.2 (DAR), and one weak D Type 4.1. An additional four donors had one variant allele each: DVII, weak D Type 1, weak D Type 3, and weak D type 100, while three donors showed a normal RHD sequence. The weak D Type 4.0 was most often linked to RHCE*ceVS.04.01, weak D Type 4.2.2 to RHCE*ceAR, and weak D Type 4.1 to RHCE*ceVS.02, while the other RHD alleles were linked to one of the common RHCE alleles. Among the weak D phenotypes in Tunisia, no novel RHD allele was found and almost 90% were caused by alleles of the weak D Type 4 cluster, of which 88% represented the weak D Type 4.0 allele. Based on established RH haplotypes for variant RHD and RHCE alleles and the lack of adverse clinical reports, we recommend D+ transfusions for patients with weak D Type 4.0 in Tunisia. © 2017 AABB.

(+)-Chlorido[(1,2,3,4-η;κP)-2'-diphenyl-phosphanyl-2-diphenyl-phosphoryl-1,1'-binaphth-yl]rhodium(I) methanol monosolvate.

PubMed

Meissner, Antje; Selle, Carmen; Drexler, Hans-Joachim; Heller, Detlef

2012-03-01

In the title complex, [RhCl(C(44)H(32)OP(2))]·CH(3)OH, the Rh(I) ion is coordinated by a naphthyl group of a partially oxidized 2,2'-bis-(diphenyl-phosphan-yl)-1,1'-binaphthyl (BINAP) ligand in a η(4) mode, one P atom of the diphenyl-phosphanyl group and one Cl atom. The P=O group does not inter-act with the Rh(I) ion but accepts an O-H⋯O hydrogen bond from the methanol solvent mol-ecule.

A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia

PubMed Central

Russell, A; Emmerson, A; Wilkinson, N; Chant, T; Sweet, D; Halliday, H; Holland, B; Davies, E

2001-01-01

OBJECTIVES—The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy.
DESIGN—Neonates (⩽ 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of ⩽ 5 × 109/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 µg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups.
RESULTS—Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p ⩽ 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001).
CONCLUSIONS—In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.
 PMID:11320043

Trends Analysis of rhBMP2 Utilization in Single-Level Anterior Lumbar Interbody Fusion in the United States

PubMed Central

Lao, Lifeng; Cohen, Jeremiah R.; Buser, Zorica; Brodke, Darrel S.; Yoon, S. Tim; Youssef, Jim A.; Park, Jong-Beom; Meisel, Hans-Joerg; Wang, Jeffrey C.

2017-01-01

Study Design: Retrospective case study. Objective: To evaluate the trends and demographics of recombinant human bone morphogenetic protein 2 (rhBMP2) utilization in single-level anterior lumbar interbody fusion (ALIF) in the United States. Methods: Patients who underwent single-level ALIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database (PearlDiver Technologies, Fort Wayne, IN), a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were analyzed for each patient. Results: A total of 921 patients were identified who underwent a single-level ALIF in this study. The average rate of single-level ALIF with rhBMP2 utilization increased (35%-48%) from 2005 to 2009, but sharply decreased to 16.7% in 2010 and 15.0% in 2011. The overall incidence of single-level ALIF without rhBMP2 (0.20 cases per 100 000 patients) was more than twice of the incidence of single-level ALIF with rhBMP2 (0.09 cases per 100 000 patients). The average rate of single-level ALIF with rhBMP2 utilization is highest in West (41.4%), followed by Midwest (33.3%), South (26.5%) and Northeast (22.2%). The highest incidence of single-level ALIF with rhBMP2 was observed in the group aged less than 65 years (compared with any other age groups, P < .001), with an incidence of 0.21 per 100 000 patients. Conclusions: The incidence of rhBMP2 utilization in single-level ALIF increased from 2006 to 2009, but decreased in 2010 and 2011. The Northeast region had the lowest incidence of rhBMP2 utilization. The group aged less than 65 years trended to have the higher incidence of single-level ALIF with rhBMP2 utilization. PMID:29662743

Trends Analysis of rhBMP2 Utilization in Single-Level Anterior Lumbar Interbody Fusion in the United States.

PubMed

Lao, Lifeng; Cohen, Jeremiah R; Buser, Zorica; Brodke, Darrel S; Yoon, S Tim; Youssef, Jim A; Park, Jong-Beom; Meisel, Hans-Joerg; Wang, Jeffrey C

2018-04-01

Retrospective case study. To evaluate the trends and demographics of recombinant human bone morphogenetic protein 2 (rhBMP2) utilization in single-level anterior lumbar interbody fusion (ALIF) in the United States. Patients who underwent single-level ALIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database (PearlDiver Technologies, Fort Wayne, IN), a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were analyzed for each patient. A total of 921 patients were identified who underwent a single-level ALIF in this study. The average rate of single-level ALIF with rhBMP2 utilization increased (35%-48%) from 2005 to 2009, but sharply decreased to 16.7% in 2010 and 15.0% in 2011. The overall incidence of single-level ALIF without rhBMP2 (0.20 cases per 100 000 patients) was more than twice of the incidence of single-level ALIF with rhBMP2 (0.09 cases per 100 000 patients). The average rate of single-level ALIF with rhBMP2 utilization is highest in West (41.4%), followed by Midwest (33.3%), South (26.5%) and Northeast (22.2%). The highest incidence of single-level ALIF with rhBMP2 was observed in the group aged less than 65 years (compared with any other age groups, P < .001), with an incidence of 0.21 per 100 000 patients. The incidence of rhBMP2 utilization in single-level ALIF increased from 2006 to 2009, but decreased in 2010 and 2011. The Northeast region had the lowest incidence of rhBMP2 utilization. The group aged less than 65 years trended to have the higher incidence of single-level ALIF with rhBMP2 utilization.

Pituitary response to repeated copulation and/or gonadotropin-releasing hormone administration in llamas and alpacas.

PubMed

Bravo, P W; Stabenfeldt, G H; Fowler, M E; Lasley, B L

1992-11-01

The response of the pituitary gland and ovary to repeated copulatory periods and/or gonadotropin-releasing hormone (GnRH, i.v. 1000 micrograms) administration was determined in llamas and alpacas. Eighty adult females (41 llamas and 39 alpacas with ovulatory follicles) were divided into three general groups for each species as follows: copulation (one or two copulations at either 6- or 24-h intervals) GnRH treatment (one or two treatments at either 6- or 24-h intervals), and combined treatment (copulation followed by GnRH treatment, or GnRH followed by copulation at either 6- or 24-h intervals). An additional control (nontreated) group was composed of 4 llamas and 4 alpacas. The first copulation or treatment with GnRH provoked LH release sufficient to cause ovulation in most of the females (alpacas, 89%; llamas, 92%); urinary pregnanediol glucuronide values, used to verify ovulation, were significantly elevated 48 h after copulation and/or GnRH treatment. A second stimulus, copulation or GnRH, provoked no LH response with concentrations similar to those in nontreated controls and in females not ovulating. Llamas and alpacas thus were refractory to a second copulatory or GnRH stimulus with regard to LH release for up to 24 h following an initial ovulatory release of LH.

Sensitive typing of reverse ABO blood groups with a waveguide-mode sensor.

PubMed

Uno, Shigeyuki; Tanaka, Torahiko; Ashiba, Hiroki; Fujimaki, Makoto; Tanaka, Mutsuo; Hatta, Yoshihiro; Takei, Masami; Awazu, Koichi; Makishima, Makoto

2018-07-01

Portable, on-site blood typing methods will help provide life-saving blood transfusions to patients during an emergency or natural calamity, such as significant earthquakes. We have previously developed waveguide-mode (WM) sensors for forward ABO and Rh(D) blood typing and detection of antibodies against hepatitis B virus and hepatitis C virus. In this study, we evaluated a WM-sensor for reverse ABO blood typing. Since reverse ABO blood typing is a method for detection of antibodies against type A and type B oligosaccharide antigens on the surface of red blood cells (RBCs), we fixed a synthetic type A or type B trisaccharide antigen on the sensor chip of the WM sensor. We obtained significant changes in the reflectance spectra from a WM sensor on type A antigen with type B plasma and type O plasma and on type B antigen with type A plasma and type O plasma, and no spectrum changes on type A antigen or type B antigen with type AB plasma. Signal enhancement with the addition of a peroxidase reaction failed to increase the sensitivity for detection on oligosaccharide chips. By utilizing hemagglutination detection using regent type A and type B RBCs, we successfully determined reverse ABO blood groups with higher sensitivity compared to a method using oligosaccharide antigens. Thus, functionality of a portable device utilizing a WM sensor can be expanded to include reverse ABO blood typing and, in combination with forward ABO typing and antivirus antibody detection, may be useful for on-site blood testing in emergency settings. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

NASA Technical Reports Server (NTRS)

Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

1996-01-01

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

High-versus low-dose erythropoietin in extremely low birth weight infants. The European Multicenter rhEPO Study Group.

PubMed

Maier, R F; Obladen, M; Kattner, E; Natzschka, J; Messer, J; Regazzoni, B M; Speer, C P; Fellman, V; Grauel, E L; Groneck, P; Wagner, M; Moriette, G; Salle, B L; Verellen, G; Scigalla, P

1998-05-01

To investigate whether a weekly 1500 IU/kg dose of recombinant human erythropoietin (rhEPO) is more effective than a dose of 750 IU/kg/week in preventing anemia and reducing the transfusion need in infants with birth weights less than 1000 gm. In a randomized, double-blind, multicenter trial, 184 infants with birth weights between 500 and 999 gm were treated with either rhEPO 750 (low-dose group) or 1500 IU/kg/week (high-dose group) from day 3 of life until 37 weeks' corrected age. Thirty-two percent of the infants in each group did not receive any transfusion during the treatment period. The total volume of erythrocytes received was similar in each group. The success rate, defined as no transfusion needed and hematocrit value 0.30 L/L or greater, was 27.6% in the low-dose and 29.5% in the high-dose group (p = 0.96). Doubling the rhEPO dose of 750 IU/kg/week is not indicated in infants with birth weights less than 1000 gm.

[Sustained release of recombinant human bone morphogenetic protein-2 combined with stromal vascular fraction cells in promoting posterolateral spinal fusion in rat model].

PubMed

Yuan, Wei; Zheng, Jun; Qian, Jinyu; Zhou, Xiaoxiao; Wang, Minghui; Wang, Xiuhui

2017-07-01

To observe the effect of stromal vascular fraction cells (SVFs) from rat fat tissue combined with sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the lumbar fusion in rat model. SVFs were harvested from subcutaneous fat of bilateral inguinal region of 4-month-old rat through the collagenase I digestion. The sustained release carrier was prepared via covalent bond of the rhBMP-2 and β-tricalcium phosphate (β-TCP) by the biominetic apatite coating process. The sustained release effect was measured by BCA method. Thirty-two rats were selected to establish the posterolateral lumbar fusion model and were divided into 4 groups, 8 rats each group. The decalcified bone matrix (DBX) scaffold+PBS, DBX scaffold+rhBMP-2/β-TCP sustained release carrier, DBX scaffold+SVFs, and DBX scaffold+rhBMP-2/β-TCP sustained release carrier+SVFs were implanted in groups A, B, C, and D respectively. X-ray films, manual spine palpation, and high-resolution micro-CT were used to evaluate spinal fusion at 8 weeks after operation; bone mineral density (BMD) and bone volume fraction were analyzed; the new bone formation was evaluated by HE staining and Masson's trichrome staining, osteocalcin (OCN) was detected by immunohistochemical staining. The cumulative release amount of rhBMP-2 was about 40% at 2 weeks, indicating sustained release effect of rhBMP-2; while the control group was almost released within 2 weeks. At 8 weeks, the combination of manual spine palpation, X-ray, and micro-CT evaluation showed that group D had the strongest bone formation (100%, 8/8), followed by group B (75%, 6/8), group C (37.5%, 3/8), and group A (12.5%, 1/8). Micro-CT analysis showed BMD and bone volume fraction were significantly higher in group D than groups A, B, and C ( P <0.05), and in group B than groups A and C ( P <0.05). HE staining, Masson's trichrome staining, and immunohistochemistry staining for OCN staining exhibited a large number of cartilage cells with bone matrix deposition, and an active osteogenic process similar to the mineralization of long bones in group D. The bone formation of group B was weaker than that of group D, and there was no effective new bone formation in groups A and C. The combination of sustained release of rhBMP-2 and freshly SVFs can significantly promote spinal fusion in rat model, providing a theoretical basis for further clinical applications.

Generation and phenotypic analysis of a transgenic line of rabbits secreting active recombinant human erythropoietin in the milk.

PubMed

Mikus, Tomás; Poplstein, Martin; Sedláková, Jirina; Landa, Vladimír; Jeníkova, Gabriela; Trefil, Pavel; Lidický, Jan; Malý, Petr

2004-10-01

Production of recombinant human erythropoietin (rhEPO) for therapeutic purposes relies on its expression in selected clones of transfected mammalian cells. Alternatively, this glycoprotein can be produced by targeted secretion into the body fluid of transgenic mammals. Here, we report on the generation of a transgenic rabbits producing rhEPO in the lactating mammary gland. Transgenic individuals are viable, fertile and transmit the rhEPO gene to the offspring. Northern blot data indicated that the expression of the transgene in the mammary gland is controlled by whey acidic protien (WAP) regulatory sequences during the period of lactation. While the hybridization with total RNA revealed the expression only in the lactating mammary gland, the highly sensitive combinatory approach using RT-PCR/hybridization technique detected a minor ectopic expression. The level of rhEPO secretion in the founder female, measured in the period of lactation, varied in the range of 60-178 and 60-162 mIU/ml in the milk and blood plasma, respectively. Biological activity of the milk rhEPO was confirmed by a standard [3H]-thymidine incorporation test. Thus, we describe the model of a rhEPO-transgenic rabbit, valuable for studies of rhEPO glycosylation and function, which can be useful for the development of transgenic approaches designed for the preparation of recombinant proteins by alternative biopharmaceutical production.

Recombinant human antithrombin expressed in the milk of non-transgenic goats exhibits high efficiency on rat DIC model.

PubMed

Yang, Hai; Li, Qing-Wang; Han, Zeng-Sheng; Hu, Jian-Hong; Li, Wen-Ye; Liu, Zhi-Bin

2009-11-01

Plasma-derived antithrombin (pAT) is often used for the treatments of disseminated intravascular coagulation (DIC) patients. In this paper, the recombinant adenovirus vector encoding human antithrombin (AT) cDNA was constructed and directly infused into the mammary gland of two goats. The recombinant human antithrombin (rhAT) was purified by heparin affinity chromatography from the goat milk, and then used in the treatment of thirty lipopolysaccharide (LPS) induced DIC rats. A high expression level of rhAT up to 2.8 g/l was obtained in the milk of goats. After purification, the recovery rate and the purity of the rhAT were up to 54.7 +/- 3.2% and 96.2 +/- 2.7%, respectively. In blood of the DIC rat model treated with rhAT, the levels of antithrombin and thrombin-antithrombin (TAT) were augmented significantly; meanwhile the consumption of fibrinogen and platelet was reduced significantly, and the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentration was restrained modest and non-significant. For the above DIC indexes, there were no differences between pAT and rhAT (P > 0.05). Our results demonstrated that the way we established is a pragmatic tool for large-scale production of rhAT, and the rhAT produced with this method has potential as a substitute for pAT in the therapy of DIC patients.

Comparison of two regimens of RhG-CSF in neutropenic neonatal septicemia: a randomized clinical trial.

PubMed

Nayeri, Fatemeh; Soheili, Habib; Kaveh, Mahbod; Oloomi Yazdi, Zohre; Shariat, Mamak; Dalili, Hosein

2011-01-01

Considering the 50% mortality rate of neonatal septicemia associated with neutropenia and increasing resistance to antibiotics, simultaneous antibiotic therapy strategies are becoming more important. However, few studies have been performed to evaluate effectiveness of RhG-CSF in the treatment of neutropenia in neonates. This randomized clinical trial was performed on 40 neutropenic neonates with septicemia who were hospitalized in Vali-e-Asr and Mirza Koochak Khan Hospitals (Tehran, Iran). The neonates were randomly divided into two equal groups RhG-CSF was administered as a subcutaneous single dose of 10 μg/kg/s.c. to neonates in group A and as 10 μg/kg/s.c./day once daily for 3 days to neonates in group B. CBC and differential count was checked 6, 24 and 48 hours after the last dose. There was no significant difference in mean birth weight, gender, age, and risk factors between two groups. Neutropenia was improved 48 hours after the last dose, whilst there was no significant statistical difference between two groups (P>0.05). The final outcome including death, duration of hospitalization and duration of antibiotics therapy after RhG-CSF administration did not differ between two groups (P>0.05). The results of this study showed that administration of a single dose of RhG-CSF (10 μg/kg) was effective in treating neonatal septicemic neutropenia.

Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

PubMed Central

2012-01-01

Background Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1) that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh) differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2), such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals. Methods ELISA was used to assess antibody responses (IgG, IgG1 and IgG3) against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140) and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5) in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37) or asymptomatic infection (N=8). Results Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control). IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody responses to defined P. falciparum invasion ligand proteins higher than those found in symptomatic (non-immune) patients. While these findings will have to be confirmed by larger studies, these results are consistent with a potential role for one or more of these invasion ligands as a component of an anti-P. falciparum vaccine in low-transmission malaria-endemic regions. PMID:23110555

Anti-D auto-immunization in a patient with weak D type 4.0.

PubMed

Ouchari, M; Chakroun, T; Abdelkefi, S; Romdhane, H; Houissa, B; Jemni Yacoub, S

2014-03-01

We report the case of a 56-year-old patient with blood group O+C-c+E-e+K-, followed for a myelodysplasic syndrome and treated by regular pheno-identical and compatible (RBCs) transfusion since December 2007. In June 2009, a positive crossmatch was found with 2 RBCs O+C-c+E-e+K-. A positive anti-body screening with a positive autocontrol was detected and anti-D was unidentified in the patient's serum. The DAT was positive (IgG) and elution identified an anti-D. The following assumptions were then made: it could be a partial D phenotype with anti-D alloantibodies or RH: 1 phenotype with an anti-D auto-antibodies. Molecular analysis by multiplex PCR and sequencing have depisted a weak D type 4.0 phenotype. In October 2009, over three months of RH:-1 RBC transfusion, the antibody screening and DAT (IgG) remained positive, and an eluate made from the patient's erythrocytes contained an anti-D. All these funding confirmed the autoimmune nature of the anti-D. This case report illustrates the importance of a well-conducted and immunohematological laboratories test in order to distinguish between auto- or allo-immune of anti-D in a RH: 1 poly-transfused patients. This distinction is of great importance for transfusion support. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Cost-Effectiveness of Screening for Primary Aldosteronism and Subtype Diagnosis in the Resistant Hypertensive Patients.

PubMed

Lubitz, Carrie C; Economopoulos, Konstantinos P; Sy, Stephen; Johanson, Colden; Kunzel, Heike E; Reincke, Martin; Gazelle, G Scott; Weinstein, Milton C; Gaziano, Thomas A

2015-11-01

Primary aldosteronism (PA) is a common and underdiagnosed disease with significant morbidity potentially cured by surgery. We aim to assess if the long-term cardiovascular benefits of identifying and treating surgically correctable PA outweigh the upfront increased costs in patients at the time patients are diagnosed with resistant hypertension (RH). A decision-analytic model compares aggregate costs and systolic blood pressure changes of 6 recommended or implemented diagnostic strategies for PA in a simulated population of at-risk RH patients. We also evaluate a 7th "treat all" strategy wherein all patients with RH are treated with a mineralocorticoid-receptor antagonist without further testing at RH diagnosis. Changes in systolic blood pressure are subsequently converted into gains in quality-adjusted life years (QALYs) by applying National Health and Nutrition Examination Survey data on concomitant risk factors to an existing cardiovascular disease simulation model. QALYs and lifetime costs were then used to calculate incremental cost-effectiveness ratios for the competing strategies. The incremental cost-effectiveness ratio for the strategy of computerized tomography (CT) followed by adrenal venous sampling (AVS) was $82,000/QALY compared with treat all. Incremental cost-effectiveness ratios for CT alone and AVS alone were $200,000/QALY and $492,000/QALY; the other strategies were more costly and less effective. Integrating differential patient-reported health-related quality of life adjustments for patients with PA, and incremental cost-effectiveness ratios for screening patients with CT followed by AVS, CT alone, and AVS alone were $52,000/QALY, $114,000/QALY, and $269,000/QALY gained. CT scanning followed by AVS was a cost-effective strategy to screen for PA among patients with RH. © 2015 American Heart Association, Inc.

Human thermal physiological and psychological responses under different heating environments.

PubMed

Wang, Zhaojun; Ning, Haoran; Ji, Yuchen; Hou, Juan; He, Yanan

2015-08-01

Anecdotal evidence suggests that many residents of severely cold areas of China who use floor heating (FH) systems feel warmer but drier compared to those using radiant heating (RH) systems. However, this phenomenon has not been verified experimentally. In order to validate the empirical hypothesis, and research the differences of human physiological and psychological responses in these two asymmetrical heating environments, an experiment was designed to mimic FH and RH systems. The subjects participating in the experiment were volunteer college-students. During the experiment, the indoor air temperature, air speed, relative humidity, globe temperature, and inner surface temperatures were measured, and subjects' heart rate, blood pressure and skin temperatures were recorded. The subjects were required to fill in questionnaires about their thermal responses during testing. The results showed that the subjects' skin temperatures, heart rate and blood pressure were significantly affected by the type of heating environment. Ankle temperature had greatest impact on overall thermal comfort relative to other body parts, and a slightly cool FH condition was the most pleasurable environment for sedentary subjects. The overall thermal sensation, comfort and acceptability of FH were higher than that of RH. However, the subjects of FH felt drier than that of RH, although the relative humidity in FH environments was higher than that of the RH environment. In future environmental design, the thermal comfort of the ankles should be scrutinized, and a FH cool condition is recommended as the most comfortable thermal environment for office workers. Consequently, large amounts of heating energy could be saved in this area in the winter. The results of this study may lead to more efficient energy use for office or home heating systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment.

PubMed

Park, Chan Woo; Choi, Min Hye; Yang, Kwang Moon; Song, In Ok

2016-09-01

To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozen-thawed embryo transfer (FET) cycles following GnRH agonist treatment. This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. GnRH agonist pretreatment increased the stimulation duration (11.5±2.1 days vs. 9.9±2.0 days) and total dose of gonadotropin (3,421±1,141 IU vs. 2,588±1,192 IU), which resulted in a significantly higher number of retrieved oocytes (10.0±8.2 vs. 7.9±6.8, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes (14.3±9.2 vs. 10.0±8.2, p=0.022) with a lower dose of gonadotropin (2,974±1,112 IU vs. 3,421±1,141 IU, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further large-scale prospective studies are required to confirm this result.

Comparison of day 3 and day 5 thyroglobulin results after thyrogen injection in differentiated thyroid cancer patients.

PubMed

Sager, Sait; Hatipoglu, Esra; Gunes, Burcak; Asa, Sertac; Uslu, Lebriz; Sönmezoğlu, Kerim

2018-06-01

It is necessary to stimulate serum thyroid-stimulating hormone (TSH) levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH) for radioactive iodine (RAI) therapy. Thyrotropin alfa (Thyrogen) has many advantages over THW. Radiation dose to laboratory staff while drawing blood for tests on the day 5 is one of the disadvantages of preferring Thyrogen. Our aim was to compare day 3 and day 5 blood test results after Thyrogen injections. In our study, Thyrogen was preferred in 32 differentiated thyroid cancer patients with a mean age of 50.5 ± 12.3 years. Thyrogen was injected on day 1 and day 2 intramuscularly in all patients before I-131 was given on day 3. A total of 22 patients received 5 mCi RAI for ablation control scintigraphy and 10 patients received 100-250 mCi RAI for ablation or therapy (high-dose group). Blood tests were performed on day 3 and day 5 after Thyrogen injections. Mean TSH level was 98.1 mg/dl for day 3 and 29.5 mg/dl for day 5. In the diagnostic group, thyroglobulin (Tg) and anti-Tg levels were nearly the same on day 3 and day 5. In the therapy group, day 5 Tg levels were higher than day 3. After Thyrogen injection of two consecutive days, blood sampling might be enough on day 3. Day 5 blood sampling may not be necessary routinely for radiation protection of laboratory staff. For the diagnostic group, if Tg and anti-Tg is normal then 5 mCi imaging may not be necessary.

[G-CSF administration following autologous peripheral blood stem cell transplantation--the effect of G-CSF level on neutrophil recovery].

PubMed

Saigo, K; Sugimoto, T; Matsuo, M; Narita, H; Ryo, R; Kumagai, S

2000-03-01

We studied the usefulness of rhG-CSF (filgrastim) administration in patients who received autologous peripheral blood stem cell transplantation (PBSCT) combined with super-high dose chemotherapy. Twenty patients received 0-8.3 micrograms/kg/day filgrastim after PBSCT. There was a significant relationship between G-CSF dose and the neutrophil recovery rate, and the highest levels of serum G-CSF tended to correlate with neutrophil recovery rate. The highest G-CSF level after 75 micrograms injection in normal volunteers is reported to be 1,500 pg/ml. On the other hand, as one patient in our series exhibited extremely high endogenous G-CSF of 11,500 pg/ml, measurements of G-CSF might reduce the over-administration of rhG-CSF.

Recombinant human thyrotropin stimulation prior to 131I therapy in toxic multinodular goitre with low radioactive iodine uptake.

PubMed

Azorín Belda, M J; Martínez Caballero, A; Figueroa Ardila, G C; Martínez Ramírez, M; Gómez Jaramillo, C A; Dolado Ardit, J I; Verdú Rico, J

Stimulation with recombinant human thyrotropin (rhTSH) increases thyroid radioiodine uptake, and is an aid to 131 I therapy in non-toxic multinodular goitre (MNG). However, there are not many studies using rhTSH prior to 131 I in toxic multinodular goitre to improve hyperthyroidism and compressive symptoms. A prospective study was conducted on patients with MNG and hyperthyroidism. Patients were recruited consecutively and divided into group I, stimulated with 0.3mg of rhTSH before radioiodine therapy, and a control group or group II, without stimulation. Thyroid function, radioiodine thyroid uptake, thyroid weight, and compressive symptoms were measured, and patients were followed-up for 9 months. Group I consisted of 16 patients (14 women), with a mean age 69.7 years, and group II with 16 patients (12 women), with a mean age 70.7 years. After stimulation with 0.3mg rhTSH in group I, 131 I uptake (RAIU) at 24h increased by 78.4%, and the estimated absorbed dose by 89.3%. In group II, the estimated absorbed dose was lower than group I after stimulation with rhTSH (29.8Gy vs. 56.4Gy; P=0.001). At 9 months of follow-up, hyperthyroidism was controlled in 87.5% of patients in group I, and 56.2% in group II (P=0.049). The mean reduction in thyroid weight was higher in group I than in group II (39.3% vs. 26.9%; P=0.017), with a tendency towards subjective improvement of compressive symptoms in group I, although non-significant. Only 2 patients described tachycardias after rhTSH administration, which were resolved with beta-blockers. Stimulation with 0.3mg of recombinant human thyrotropin prior to radioiodine therapy achieves a reduction in thyroid weight and functional improvement in patients with hyperthyroidism and multinodular goitre with low uptake, and with no need for hospital admission. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

INRA, a new high-frequency antigen in the INDIAN (IN023) blood group system

PubMed Central

Joshi, Sanmukh R.; Sheladiya, Ankita; Mendapara-Dobariya, Kinjal V.

2017-01-01

BACKGROUND: The INDIAN blood group system comprises 4 antigens sensitive to enzymes and 2-aminoethyl isothiouronium bromide (AET). AIM: The patient's antibody was investigated for its specificity to the high-frequency antigens (HFA) of this system. MATERIAL AND METHODS: Low ionic strength solution (LISS)-tube/LISS-indirect antiglobulin test (IAT) methods were used. The patient's red blood cells (RBCs) were tested with antisera to HFA. Her antibody was tested with RBCs lacking the HFA. Furthermore, it was tested with RBCs as untreated or treated with enzyme or AET. The genetic sequence was studied for mutation in CD44 gene that encodes INDIAN antigens. RESULTS: The patient was grouped A1B, RhD+, antibody screening test positive, direct antiglobulin test negative. A negative autocontrol test had suggested to the alloantibody being present. Antibody had agglutinated RBCs in LISS-tube at RT and by LISS-IAT at 37°C. The RBCs of the 11-cell panel, those lacking HFA and from 50 random donors, were agglutinated by her antibody indicating its specificity to the HFA, though the RBCs of Lu (a-b-)/In (Lu) type showed a weaker reaction. The patient's RBCs were agglutinated by antisera to a number of the enzyme-sensitive HFA, including those of INDIAN blood groups. The antibody showed reduced reactivity with the RBCs treated with papain, chymotrypsin, and AET but resistant to trypsin and dithiothreitol. The patient's genetic sequence revealed a novel homozygous mutation 449G>A in exon 5 of CD44. CONCLUSION: The antibody to enzyme sensitive HFA was tested for serological and molecular genetics studies and found to be directed to the novel HFA, named as INRA of the INDIAN blood group system and was assigned a numerical symbol IN: 005 by the International Society of Blood Transfusion (ISBT). PMID:28970678

Severe hypertriglyceridemia in Puerto Rico blood donors: a population study 2009-2011.

PubMed

Morales-Borges, Raúl H; Merced, Carmen

2012-01-01

Puerto Rico blood donor issues has been identified in cases of severe hypertriglyceridemia presenting as turbid. Blood donations resulting in milky serum must be discarded. They are discarded because we cannot properly test the donation. This is the first report where we correlate turbidity and cardiovascular risk factors in the Puerto Rico population as well as blood types O and A, Rh (+) with dyslipidemia. Blood donors should be screened in more details regarding cardiovascular and metabolic risks to avoid problems with recruitment and retention strategies.

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study

PubMed Central

Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Şatıroğlu, Hakan

2010-01-01

Objective To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). Material and Methods The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. Results There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Conclusion Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI. PMID:24591934

Recovery from adverse effects of heat stress on slow-growing chicks in the tropics 1: Effect of ascorbic acid and different levels of betaine.

PubMed

Attia, Y A; Hassan, R A; Qota, E M A

2009-06-01

Three hundreds, 21 d-old slow-growing chicks were randomly divided among 5 treatments, of 5 replicates each. Each replicate contained 12 unsexed chicks housed in (1 x 1) a floor pen. A group was kept under thermoneutral condition at 28 +/- 4 degrees C and RH was 55 +/- 3% during 21-84 d of age (positive control) and fed corn-soybean meal diet. The other four groups were kept for three successive days per week under heat stress (HS) at 38 +/- 1.4 degrees C and 49 +/- 2% RH from 12.00 to 16.00 pm. Chicks in HS treatments were fed corn-soybean meal diet without (negative control) or with 250 mg AA/kg diet and Bet at 0.5 and 1 g/kg diet. HS decreased productive performance, increased (P < 0.05) meat dry matter, plasma triglyceride and serum calcium whereas decreased (P > 0.05) plasma glucose, serum total protein and water holding capacity (WHC) of meat. AA and 1 g of Bet/kg diet was equally potent for partial relief (P < 0.05) of the negative effect of HS on growth, increased (P < 0.05) feed intake, protein digestibility (P < 0.05), dressing out percentage, liver and giblets, whilst improved (P < 0.05) feed conversion ratio (FCR). Also, a complete recovery from the negative effect (P < 0.05) of HS shown on plasma glucose and partial recovery (P < 0.05) observed in total protein, triglyceride, blood pH, packed cell volume (PCV), hemoglobin (Hgb), rectal temperature (RT) and respiration rate (RR) and improved humoral immune competence to sheep red blood cell (SBRCs) test.

Ghrelin suppresses the GnRH-induced preovulatory gonadotropin surge in dairy heifers.

PubMed

Chouzouris, T M; Dovolou, E; Dafopoulos, K; Georgoulias, P; Vasileiou, N G; Fthenakis, G C; Anifandis, G; Amiridis, G S

2016-10-01

Ghrelin, a known growth hormone (GH) secretagogue, alters gonadotropin secretion in many species. Our objectives were to study the effects of ghrelin, on GH, LH, FSH secretion, and on luteal function of the ensuing estrous cycle in cattle. The estrous cycles of eight heifers were synchronized with progesteron releasing intravaginal device, and ovulation was induced with GnRH. Eight animals were treated with 1.5 μg kg(-1) bovine ghrelin (group Ghr, n = 4) or saline (group C, n = 4). Starting with the first ghrelin injection, 13 blood samples were collected over a 4-hour period for the determination of ghrelin, GH, LH, and FSH concentration. Progesterone levels were measured in samples collected every other day after estrus expression. Data were analyzed by repeated measures of ANOVA followed by Bonferroni post hoc testing and t test. In group Ghr, ghrelin concentration increased significantly 15 minutes after the first injection and remained in elevated levels until the 90th minute after the last injection. At the time of third ghrelin injection, GH was significantly higher in the Ghr group compared with C (17.1 ± 1.3 vs. 2.6 ± 0.3 ng mL(-1), P < 0.0001). Similar differences were found for the next three samples collected 15, 30, and 60 minutes later; no difference was evident after 90 minutes. In group Ghr, the area under the curve for LH and FSH were significantly reduced compared with the ones of group C (266 ± 10.3 vs. 331.9 ± 7.3, P = 0.007 and 102.3 ± 2.0 vs. 134.9 ± 5.5, P < 0.005 for LH and FSH respectively). At particular time points the concentration of the two gonadotrophins in group Ghr was significantly lower than those of group C (15, 30, 45, 75, and 90 and 60, 75, 90, 120, and 150 minutes after GnRH administration for LH and FSH respectively). The duration of the following estrous cycle was shorter (P = 0.004) in group Ghr (19.0 ± 0.4 days) compared with C (21.8 ± 0.5 days). In days 4, 6, 8, 10, and 14, progesterone concentration was lower (P < 0.05) in group Ghr compared with C; similarly the progesterone area under the curve for group Ghr (113.1 ± 4.8) was suppressed (P = 0.007) compared with that of C (141 ± 4.8). These results imply that ghrelin acts on pituitary causing impaired response to the GnRH stimulus, and it is likely to affect luteinization of the cellular compartment of the preovulatory follicle, and/or to suppress steroidogenetic activity of the luteal cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose-response characteristics of neonatal exposure to genistein on pituitary responsiveness to gonadotropin releasing hormone and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in postpubertal castrated female rats.

PubMed

Faber, K A; Hughes, C L

1993-01-01

Estrogen exposure during critical periods of development promotes androgenization of the brain, which is reflected in altered morphology, behavior, and cyclic hormone secretion in females. Previous work in our laboratory demonstrated that neonatal female rats injected with pharmaceutical or naturally occurring estrogens had decreased GnRH-induced LH secretion and increased volume of the SDN-POA as 42 day castrates. The current experiment defines the dose-response characteristics of neonatal exposure to the isoflavonoid phytoestrogen genistein (G) on pituitary sensitivity to GnRH and SDN-POA volume. Litters of rat pups received subcutaneous injections of either corn oil, 1, 10, 100, 200, 400, 500, or 1000 micrograms of G on days 1 to 10 of life. The litters were ovariectomized and weaned on day 21. On day 42 blood was drawn from right atrial catheters immediately prior to, 5, 10, 15, and 30 min following a single injection of 50 ng/kg of GnRH. Only the 10 micrograms dose of G was associated with increased pituitary response to GnRH, while progressive increases in exposure levels of G were associated with decreasing LH secretion. The SDN-POA volume was increased in only the 500 micrograms and 1000 micrograms exposure groups compared to controls. The results confirm that low doses of G have nonandrogenizing, pituitary-sensitizing effects, while higher doses of G mimic the more typical effects of estrogens. The use of both morphologic and physiologic end points more completely defines the reproductive consequences of environmental estrogen exposure during critical periods of CNS development.

Evaluation of the Potential for Secondary Kill for Ingested Insecticides in the Common Bed Bug (Hemiptera: Cimicidae).

PubMed

Matos, Yvonne K; Sierras, Angela; Schal, Coby

2017-06-01

Baits are a preferred method of urban pest management. Baits enable more targeted insecticide applications with a fraction of the active ingredient used in residual sprays. Bait translocation by foragers, and consequent secondary kill of nonforagers, enhances bait effectiveness in social insects, and in other group-living species like German cockroaches (Blattella germanica L.). We investigated the potential for secondary kill in bed bugs (Cimex lectularius L.), another gregarious species, using a liquid bait. We first investigated whether blood-fed adults enhance nymph survivorship within aggregations by increasing the local relative humidity (RH) and providing fecal nutrients. Higher RH (50% and 95%) resulted in greater survivorship of first instars compared with 0% RH. Therefore, in subsequent experiments, we controlled RH to decouple its effect on nymph survivorship from effects of fecal nutrients. The presence of fed or unfed adults did not increase unfed first instar survivorship, suggesting that if nymphs ingested feces, its nutritional benefits were minimal. Nymph survivorship was unaffected by the presence of adult males fed fipronil or clothianidin, suggesting that unlike in cockroaches, highly effective insecticides might not be effective as secondary kill toxicants in bed bugs. To directly compare secondary kill in first-instar bed bugs and B. germanica, we exposed both to insecticide-laden adult B. germanica feces. Whereas first-instar B. germanica died in the presence of insecticide-laden feces, bed bugs did not. We, therefore, conclude that secondary kill with neuroactive insecticides will likely not be a significant factor in bed bug population suppression. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Silver nanoparticles synthesized with Rumex hymenosepalus extracts: effective broad-spectrum microbicidal agents and cytotoxicity study.

PubMed

Rodríguez-León, Ericka; Íñiguez-Palomares, Ramón A; Navarro, Rosa Elena; Rodríguez-Beas, César; Larios-Rodríguez, Eduardo; Alvarez-Cirerol, Francisco J; Íñiguez-Palomares, Claudia; Ramírez-Saldaña, Maricela; Hernández Martínez, Javier; Martínez-Higuera, Aarón; Galván-Moroyoqui, José Manuel; Martínez-Soto, Juan Manuel

2017-08-21

We synthesized silver nanoparticles using Rumex hymenosepalus root extract (Rh). Nanoparticles were subjected to a purification process and final product is a composite of Rh and silver nanoparticles (AgNPsC). Transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were used to perform a microstructure study. Additionally, two fractions (RhA and RhB) were obtained from the original extract by filtration with tetrahydrofuran (THF); both fractions were analyzed using UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FT-IR), and 2,2-diphenyl-1-picrylhydrazyl (DPPH); total polyphenol content was also determined. Separate inhibition tests for AgNPsC and RhA and RhB were applied to Gram-positive bacteria, Gram-negative bacteria, and yeast (Candida albicans) using the well diffusion method. Extract fractions were found to have inhibitory effects only over Gram-positive bacteria, and silver nanoparticles showed inhibitory effects over all the evaluated microorganisms. Cytotoxicity was evaluated using the tetrazolium dye (MTT) assay in mononuclear peripheral blood cells. In addition, we assessment AgNPsC in THP-1 monocyte cell line, using the cell viability estimation by trypan blue dye exclusion test (TB) and Live/Dead (LD) cell viability assays by confocal microscopy.

Reduced bleeding events with subcutaneous administration of recombinant human factor IX in immune-tolerant hemophilia B dogs.

PubMed

Russell, Karen E; Olsen, Eva H N; Raymer, Robin A; Merricks, Elizabeth P; Bellinger, Dwight A; Read, Marjorie S; Rup, Bonita J; Keith, James C; McCarthy, Kyle P; Schaub, Robert G; Nichols, Timothy C

2003-12-15

Intravenous administration of recombinant human factor IX (rhFIX) acutely corrects the coagulopathy in hemophilia B dogs. To date, 20 of 20 dogs developed inhibitory antibodies to the xenoprotein, making it impossible to determine if new human FIX products, formulations, or methods of chronic administration can reduce bleeding frequency. Our goal was to determine whether hemophilia B dogs rendered tolerant to rhFIX would have reduced bleeding episodes while on sustained prophylactic rhFIX administered subcutaneously. Reproducible methods were developed for inducing tolerance to rhFIX in this strain of hemophilia B dogs, resulting in a significant reduction in the development of inhibitors relative to historical controls (5 of 12 versus 20 or 20, P <.001). The 7 of 12 tolerized hemophilia B dogs exhibited shortened whole blood clotting times (WBCTs), sustained detectable FIX antigen, undetectable Bethesda inhibitors, transient or no detectable antihuman FIX antibody titers by enzyme-linked immunosorbent assay (ELISA), and normal clearance of infused rhFIX. Tolerized hemophilia B dogs had 69% reduction in bleeding frequency in year 1 compared with nontolerized hemophilia B dogs (P =.0007). If proven safe in human clinical trials, subcutaneous rhFIX may provide an alternate approach to prophylactic therapy in selected patients with hemophilia B.

A Novel Low-Molecular-Weight Compound Enhances Ectopic Bone Formation and Fracture Repair

PubMed Central

Wong, Eugene; Sangadala, Sreedhara; Boden, Scott D.; Yoshioka, Katsuhito; Hutton, William C.; Oliver, Colleen; Titus, Louisa

2013-01-01

Background: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is expensive and may cause local side effects. A small synthetic molecule, SVAK-12, has recently been shown in vitro to potentiate rhBMP-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. The aims of this study were to test the ability of SVAK-12 to enhance bone formation in a rodent ectopic model and to test whether a single percutaneous injection of SVAK-12 can accelerate callus formation in a rodent femoral fracture model. Methods: Collagen disks with rhBMP-2 alone or with rhBMP-2 and SVAK-12 were implanted in a standard athymic rat chest ectopic model, and radiographic analysis was performed at four weeks. In a second set of rats (Sprague-Dawley), SVAK-12 was percutaneously injected into the site of a closed femoral fracture. The fractures were analyzed radiographically and biomechanically (with torsional testing) five weeks after surgery. Results: In the ectopic model, there was dose-dependent enhancement of rhBMP-2 activity with use of SVAK-12 at doses of 100 to 500 μg. In the fracture model, the SVAK-12-treated group had significantly higher radiographic healing scores than the untreated group (p = 0.028). Biomechanical testing revealed that the fractured femora in the 200 to 250-μg SVAK-12 group were 43% stronger (p = 0.008) and 93% stiffer (p = 0.014) than those in the control group. In summary, at five weeks the femoral fracture group injected with SVAK-12 showed significantly improved radiographic and biomechanical evidence of healing compared with the controls. Conclusions: A single local dose of a low-molecular-weight compound, SVAK-12, enhanced bone-healing in the presence of low-dose exogenous rhBMP-2 (in the ectopic model) and endogenous rhBMPs (in the femoral fracture model). Clinical Relevance: This study demonstrates that rhBMP-2 responsiveness can be enhanced by a novel small molecule, SVAK-12. Local application of anabolic small molecules has the potential for potentiating and accelerating fracture-healing. Use of this small molecule to lower required doses of rhBMPs might both decrease their cost and improve their safety profile. PMID:23467869

Immunosafety of recombinant human C1-inhibitor in hereditary angioedema: evaluation of ige antibodies.

PubMed

Hack, C Erik; Relan, Anurag; Baboeram, Aartie; Oortwijn, Beatrijs; Versteeg, Serge; van Ree, Ronald; Pijpstra, Rienk

2013-04-01

Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency. The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions. In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow's milk by the ImmunoCAP(®) Specific IgE blood test system. 130 HAE patients and 14 healthy subjects received 300 administrations of rhC1INH, 65 subjects (47.4 %) on one occasion; 72 (52.6 %) on at least two occasions (range 2-12; median 2). Five subjects had pre-existing anti-rabbit epithelium IgE; the subject with the highest levels and a previously undisclosed rabbit allergy developed an anaphylactic reaction upon first exposure to rhC1INH, whereas the other four subjects with lower pre-existing IgE levels (Class 1-3), did not. No other anaphylactic reactions were identified in any of the subjects exposed to rhC1INH. Analysis of post-exposure samples revealed that the risk of inducing new or boosting existing IgE responses to rabbit or cow's milk allergens was negligible. The propensity of rhC1INH to induce IgE antibodies following repeated administration of rhC1INH is low. Subjects with substantially elevated anti-rabbit epithelium IgE antibodies and/or clinical allergy to rabbits may have an increased risk for an allergic reaction. No other risk factors for allergic reactions to rhC1INH have been identified.

Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.

PubMed

Yin, Weiqin; Xu, Shiqing; Wang, Zai; Liu, Honglin; Peng, Liang; Fang, Qing; Deng, Tingting; Zhang, Wenjian; Lou, Jinning

2018-01-01

GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, α-SMA, fibronectin, and inflammation factors MCP-1 and TNFα in tubular tissue and human proximal tubular cells (HK-2 cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-κB, MAPK in both diabetic tubular tissue and HK-2 cells. The inhibition of the expression of TNFα, MCP-1, collagen I and α-SMA in HK-2 cells by GLP-1 could be mimicked by blocking NF-κB or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injury via inhibiting phosphorylation of MAPK and NF-κB. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Rectal hyposensitivity and functional anorectal outlet obstruction are common entities in patients with functional constipation but are not significantly associated.

PubMed

Lee, Tae Hee; Lee, Joon Seong; Hong, Su Jin; Jeon, Seong Ran; Kwon, Soon Ha; Kim, Wan Jung; Kim, Hyun Gun; Cho, Won Young; Cho, Joo Young; Kim, Jin-Oh; Lee, Ji Sung

2013-01-01

The causes of functional anorectal outlet obstruction (outlet obstruction) include functional defecation disorder (FDD), rectocele, and rectal intussusception (RI). It is unclear whether outlet obstruction is associated with rectal hyposensitivity (RH) in patients with functional constipation (FC). The aim of this study was to determine the association between RH and outlet obstruction in patients with FC. This was a retrospective study using a prospectively collected constipation database, and the population comprised 107 patients with FC (100 females; median age, 49 years). We performed anorectal manometry, defecography, rectal barostat, and at least two tests (balloon expulsion test, electromyography, or colon transit time study). RH was defined as one or more sensory threshold pressures raised beyond the normal range on rectal barostat. We investigated the association between the presence of RH and an outlet obstruction such as large rectocele (> 2 cm in size), RI, or FDD. Forty patients (37.4%) had RH. No significant difference was observed in RH between patients with small and large rectoceles (22 [44.9%] vs. 18 [31%], respectively; p = 0.140). No significant difference was observed in RH between the non-RI and RI groups (36 [36.7%] vs. 4 [30.8%], respectively; p = 0.599). Furthermore, no significant difference in RH was observed between the non-FDD and FDD groups (19 [35.8%] vs. 21 [38.9%], respectively; p = 0.745). RH and outlet obstruction are common entities but appear not to be significantly associated.

Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Augmented Sheep Spinal Fusion.

PubMed

Pan, Hsin Chuan; Lee, Soonchul; Ting, Kang; Shen, Jia; Wang, Chenchao; Nguyen, Alan; Berthiaume, Emily A; Zara, Janette N; Turner, A Simon; Seim, Howard B; Kwak, Jin Hee; Zhang, Xinli; Soo, Chia

2017-07-01

Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Organization for the coverage of the transfusional needs of patients with hemoglobinopathy at the Établissement français du sang Bretagne].

PubMed

Thibert, J-B; Danic, B; Delamaire, M; Delugin, L; Dugor, C; Le Vacon, F; Nimubona, S; Treussard, D; Vasse, J; Semana, G

2015-03-01

Brittany is a low prevalence region for hemoglobinopathies. Despite of that, the number of patients is increasing each year. In 2013, 140 patients were known at the EFS Bretagne, and medical consultations are growing for 50% each year since 2011. The consequence is an increase of needs of 22% of compatible packed red blood cells. To anticipate the announced progress, various actions were implemented as study groups, creation of a new informatic prescription for red blood cells phenotyping, promotion of donation, transfusion organisation. Fifthty-nine percent of the 400 ABO RH-KELL, FY, JK, MNS 3, 4, red blood cells were realised on the basis of this new informatic prescription, as the 99% of the packed red blood cells identified Fy (a- b-). So, 92% of the compatible transfused packed red blood cells were already in stock when the patients needed them. In Brittany, that organisation leads to assume qualitative and quantitative transfusion for sickle cell disease in more than 90% of cases, with fast distribution. In the same time promotion of donation is done to increase the diversity of donors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A high-resolution map of the Nile tilapia genome: a resource for studying cichlids and other percomorphs

PubMed Central

2012-01-01

Background The Nile tilapia (Oreochromis niloticus) is the second most farmed fish species worldwide. It is also an important model for studies of fish physiology, particularly because of its broad tolerance to an array of environments. It is a good model to study evolutionary mechanisms in vertebrates, because of its close relationship to haplochromine cichlids, which have undergone rapid speciation in East Africa. The existing genomic resources for Nile tilapia include a genetic map, BAC end sequences and ESTs, but comparative genome analysis and maps of quantitative trait loci (QTL) are still limited. Results We have constructed a high-resolution radiation hybrid (RH) panel for the Nile tilapia and genotyped 1358 markers consisting of 850 genes, 82 markers corresponding to BAC end sequences, 154 microsatellites and 272 single nucleotide polymorphisms (SNPs). From these, 1296 markers could be associated in 81 RH groups, while 62 were not linked. The total size of the RH map is 34,084 cR3500 and 937,310 kb. It covers 88% of the entire genome with an estimated inter-marker distance of 742 Kb. Mapping of microsatellites enabled integration to the genetic map. We have merged LG8 and LG24 into a single linkage group, and confirmed that LG16-LG21 are also merged. The orientation and association of RH groups to each chromosome and LG was confirmed by chromosomal in situ hybridizations (FISH) of 55 BACs. Fifty RH groups were localized on the 22 chromosomes while 31 remained small orphan groups. Synteny relationships were determined between Nile tilapia, stickleback, medaka and pufferfish. Conclusion The RH map and associated FISH map provide a valuable gene-ordered resource for gene mapping and QTL studies. All genetic linkage groups with their corresponding RH groups now have a corresponding chromosome which can be identified in the karyotype. Placement of conserved segments indicated that multiple inter-chromosomal rearrangements have occurred between Nile tilapia and the other model fishes. These maps represent a valuable resource for organizing the forthcoming genome sequence of Nile tilapia, and provide a foundation for evolutionary studies of East African cichlid fishes. PMID:22672252

Efficacy of rhBMP-2 Loaded PCL/β-TCP/bdECM Scaffold Fabricated by 3D Printing Technology on Bone Regeneration.

PubMed

Bae, Eun-Bin; Park, Keun-Ho; Shim, Jin-Hyung; Chung, Ho-Yun; Choi, Jae-Won; Lee, Jin-Ju; Kim, Chang-Hwan; Jeon, Ho-Jun; Kang, Seong-Soo; Huh, Jung-Bo

2018-01-01

This study was undertaken to evaluate the effect of 3D printed polycaprolactone (PCL)/ β -tricalcium phosphate ( β -TCP) scaffold containing bone demineralized and decellularized extracellular matrix (bdECM) and human recombinant bone morphogenetic protein-2 (rhBMP-2) on bone regeneration. Scaffolds were divided into PCL/ β -TCP, PCL/ β -TCP/bdECM, and PCL/ β -TCP/bdECM/BMP groups. In vitro release kinetics of rhBMP-2 were determined with respect to cell proliferation and osteogenic differentiation. These three reconstructive materials were implanted into 8 mm diameter calvarial bone defect in male Sprague-Dawley rats. Animals were sacrificed four weeks after implantation for micro-CT, histologic, and histomorphometric analyses. The findings obtained were used to calculate new bone volumes (mm 3 ) and new bone areas (%). Excellent cell bioactivity was observed in the PCL/ β -TCP/bdECM and PCL/ β -TCP/bdECM/BMP groups, and new bone volume and area were significantly higher in the PCL/ β -TCP/bdECM/BMP group than in the other groups ( p < .05). Within the limitations of this study, bdECM printed PCL/ β -TCP scaffolds can reproduce microenvironment for cells and promote adhering and proliferating the cells onto scaffolds. Furthermore, in the rat calvarial defect model, the scaffold which printed rhBMP-2 loaded bdECM stably carries rhBMP-2 and enhances bone regeneration confirming the possibility of bdECM as rhBMP-2 carrier.

Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure

PubMed Central

Wang, Guogan; Wang, Pengbo; Li, Yishi; Liu, Wenxian; Bai, Shugong; Zhen, Yang; Li, Dongye; Yang, Ping; Chen, Yu; Hong, Lang; Sun, Jianhui; Chen, Junzhu; Wang, Xian; Zhu, Jihong; Hu, Dayi; Li, Huimin; Wu, Tongguo; Huang, Jie; Tan, Huiqiong; Zhang, Jian; Liao, Zhongkai; Yu, Litian; Mao, Yi; Ye, Shaodong; Feng, Lei; Hua, Yihong; Ni, Xinhai; Zhang, Yuhui; Wang, Yang; Li, Wei; Luan, Xiaojun; Sun, Xiaolu; Wang, Sijia

2016-01-01

Abstract The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863–2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (−7.74 ± 5.95 vs −1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34–4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.) PMID:26945407

Dynamics of progesterone, TNF-a and a metabolite of PGF2a in blood plasma of beef cows following embryo transfer

USDA-ARS?s Scientific Manuscript database

Lactating beef cows received an embryo along with no treatment (control; n = 16), controlled internal drug releasing device (CIDR; n = 16), human chorionic gonadotropin (hCG; n = 15), or gonadotropin releasing hormone (GnRH; n = 15) to assess the effectiveness of these treatments in increasing blood...

Effect of varying light intensity on blood physiological reactions of broiler chickens grown to heavy weights

USDA-ARS?s Scientific Manuscript database

This study investigated effects of varying levels of light intensities (25, 10, 5, 2.5, and 0.2 lx) from 22 to 56 d of age at 50% RH on blood acid-base balance, metabolites, and electrolytes of heavy broilers reared under environmentally controlled conditions. Four identical trials were conducted wi...

Radioiodine remnant ablation in differentiated thyroid cancer after combined endogenous and exogenous TSH stimulation.

PubMed

Vrachimis, A; Schober, O; Riemann, B

2012-01-01

Radioiodine remnant ablation (RRA) after (near-)total thyroidectomy (TE) is a key element in patients with differentiated thyroid cancer (DTC). The use of exogenous TSH stimulation (rhTSH) prior to RRA has shown promising results as compared to conventional thyroid hormone withdrawal (THW). As yet, the efficacy of RRA after brief THW and single rhTSH administration has not been assessed. The study sample comprised 147 patients with DTC referred to our center between May 2008 and September 2010. All patients received TE with subsequent RRA. None of these 147 patients had evidence of distant metastasis. 93 patients had endogenous TSH stimulation 4-5 weeks after surgery (group I) and twenty-six received two rhTSH injections (group II). 28 patients were treated with a single rhTSH injection after a brief THW (group III). RRA-Efficacy was assessed three months after therapy by diagnostic whole-body scan and measurement of the tumour marker thyroglobulin (Tg) under TSH stimulation. Three categories of success were defined for remnant ablation. Based on the definition of successful remnant ablation no visible uptake and a Tg ≤ 2.0 ng/ml (category 1) was seen in 62/93 patients in group I, in 17/26 patients in group II (p = n.s.) and in 12/28 patients in group III (p < 0.05). Visible radioiodine uptake and a Tg ≤ 2.0 ng/ml (category 2) was seen in 16/28 patients of group III and thus significantly more frequent than in group I (28/93 patients) (p < 0.01). However, patients in group III (16/28 patients) and group II (8/26 patients) showed no significant difference in this category (p = n.s.). Visible radioiodine uptake and a Tg > 2.0 ng/ml (category 3) was found in 3/93 patients in group I and 1/26 patients in group II but in no patient in group III. The third strategy of remnant ablation using a single injection of rhTSH after a brief THW period resulted in a significant higher rate of patients with residual uptake in the thyroid bed and a Tg level below 2 ng/ml three months after remnant ablation in comparison to THW. However, the overall efficacy of the third protocol was not significantly different as compared to two rhTSH injections. Under the aspect of the supply shortage of rhTSH the combined endogenous and exogenous TSH stimulation may be an attractive alternative for remnant ablation in differentiated thyroid cancer.

A prospective, randomized pilot study on the safety and efficacy of recombinant human growth and differentiation factor-5 coated onto β-tricalcium phosphate for sinus lift augmentation.

PubMed

Koch, Felix P; Becker, Jürgen; Terheyden, Hendrik; Capsius, Björn; Wagner, Wilfried

2010-11-01

The aim of this prospective, randomized clinical trial was to investigate the potential of recombinant human growth and differentiation factor-5 (rhGDF-5) coated onto β-tricalcium phosphate (β-TCP) (rhGDF-5/β-TCP) to support bone formation after sinus lift augmentation. In total, 31 patients participated in this multicenter clinical trial. They required a two-stage unilateral maxillary sinus floor augmentation (residual bone height <5 mm). According to a parallel-group design, the patients were randomized to three treatment groups: (a) augmentation with rhGDF-5/β-TCP and a 3-month healing period, (b) augmentation with rhGDF-5/β-TCP and a 4-month healing period and (c) medical device β-TCP mixed with autologous bone and a 4-month healing period. The primary study objective was the area of newly formed bone within the augmented area as assessed by histomorphometric evaluation of trephine bur biopsies. The osseous regeneration was similar in each treatment group; the amount of newly formed bone ranged between 28% (± 15.5%) and 31.8% (± 17.9%). Detailed analysis of histological data will be published elsewhere. As secondary efficacy variables, the augmentation height at the surgery site was measured by radiography. The largest augmentation was radiologically achieved in the rhGDF-5/β-TCP - 3-month and the rhGDF-5/β-TCP - 4-month treatment groups. As safety parameters, adverse events were recorded and anti-drug antibody levels were evaluated. Most of the adverse events were judged as unrelated to the study medication. Four out of 47 (8.5%) implants failed in patients treated with rhGDF-5/β-TCP, a result that is in agreement with the general implant failure rate of 5-15%. Transiently very low amounts of anti-rhGDF-5 antibodies were detected in some patients who received rhGDF-5, which was not related to the bone formation outcome. rhGDF-5/β-TCP was found to be effective and safe as the control treatment with autologous bone mixed β-TCP in sinus floor augmentation. Thus, further investigation regarding efficacy and safety will be carried out in larger patient populations. © 2010 John Wiley & Sons A/S.

Does polycystic ovarian morphology influence the response to treatment with pulsatile GnRH in functional hypothalamic amenorrhea?

PubMed

Dumont, Agathe; Dewailly, Didier; Plouvier, Pauline; Catteau-Jonard, Sophie; Robin, Geoffroy

2016-04-29

Pulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called "FHA-PCOM", has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and "FHA-PCOM" patients in order to search for an eventual impact of PCOM. Retrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 "FHA-PCOM" patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation. The two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with "FHA-PCOM". There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates. Pulsatile GnRH seems to be a successful and safe method for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM.

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model

PubMed Central

Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

2015-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration. PMID:26376304

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

PubMed

Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

2015-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

The nervus terminalis in the mouse: light and electron microscopic immunocytochemical studies.

PubMed

Jennes, L

1987-01-01

The distribution of gonadotropin-releasing hormone (GnRH)-containing neurons and fibers in the olfactory bulb was studied with light and electron microscopic immunohistochemistry in combination with retrograde transport of "True Blue" and horseradish peroxidase and lesion experiments. GnRH-positive neurons are found in the septal roots of the nervus terminalis, in the ganglion terminale, intrafascicularly throughout the nervus terminalis, in a dorso-ventral band in the caudal olfactory bulb, in various layers of the main and accessory olfactory bulb, and in the basal aspects of the nasal epithelium. Electron microscopic studies show that the nerve fibers in the nervus terminalis are not myelinated and are not surrounded by Schwann cell sheaths. In the ganglion terminale, "smooth" GnRH neurons are seen in juxtaposition to immunonegative neurons. Occasionally, axosomatic specializations are found in the ganglion terminale, but such synaptic contacts are not seen intrafascicularly in the nervus terminalis. Retrograde transport studies indicate that certain GnRH neurons in the septal roots of the nervus terminalis were linked to the amygdala. In addition, a subpopulation of nervus terminalis-related GnRH neurons has access to fenestrated capillaries whereas other GnRH neurons terminate at the nasal epithelium. Lesions of the nervus terminalis caudal to the ganglion terminale result in sprouting of GnRH fibers at both sites of the knife cut. The results suggest that GnRH in the olfactory system of the mouse can influence a variety of target sites either via the blood stream, via the external cerebrospinal fluid or via synaptic/asynaptic contacts with, for example, the receptor cells in the nasal mucosa.

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies

PubMed Central

2011-01-01

Background Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains. Results The plant-codon-optimized hIGF-I was introduced into rice via Agrobacterium-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. In vitro functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats. Conclusion Our findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I. PMID:21486461

Radiographic comparison of different concentrations of recombinant human bone morphogenetic protein with allogenic bone compared with the use of 100% mineralized cancellous bone allograft in maxillary sinus grafting.

PubMed

Froum, Stuart J; Wallace, Stephen; Cho, Sang-Choon; Khouly, Ismael; Rosenberg, Edwin; Corby, Patricia; Froum, Scott; Mascarenhas, Patrick; Tarnow, Dennis P

2014-01-01

The purpose of this study was to radiographically evaluate, then analyze, bone height, volume, and density with reference to percentage of vital bone after maxillary sinuses were grafted using two different doses of recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ACS) combined with mineralized cancellous bone allograft (MCBA) and a control sinus grafted with MCBA only. A total of 18 patients (36 sinuses) were used for analysis of height and volume measurements, having two of three graft combinations (one in each sinus): (1) control, MCBA only; (2) test 1, MCBA + 5.6 mL of rhBMP-2/ACS (containing 8.4 mg of rhBMP-2); and (3) test 2, MCBA + 2.8 mL of rhBMP-2/ACS (containing 4.2 mg of rhBMP-2). The study was completed with 16 patients who also had bilateral cores removed 6 to 9 months following sinus augmentation. A computer software system was used to evaluate 36 computed tomography scans. Two time points where selected for measurements of height: The results indicated that height of the grafted sinus was significantly greater in the treatment groups compared with the control. However, by the second time point, there were no statistically significant differences. Three weeks post-surgery bone volume measurements showed similar statistically significant differences between test and controls. However, prior to core removal, test group 1 with the greater dose of rhBMP-2 showed a statistically significant greater increase compared with test group 2 and the control. There was no statistically significant difference between the latter two groups. All three groups had similar volume and shrinkage. Density measurements varied from the above results, with the control showing statistically significant greater density at both time points. By contrast, the density increase over time in both rhBMP groups was similar and statistically higher than in the control group. There were strong associations between height and volume in all groups and between volume and new vital bone only in the control group. There were no statistically significant relationships observed between height and bone density or between volume and bone density for any parameter measured. More cases and monitoring of the future survival of implants placed in these augmented sinuses are needed to verify these results.

Gonadotropin-releasing hormone agonist trigger increases the number of oocytes and embryos available for cryopreservation in cancer patients undergoing ovarian stimulation for fertility preservation.

PubMed

Pereira, Nigel; Kelly, Amelia G; Stone, Logan D; Witzke, Justine D; Lekovich, Jovana P; Elias, Rony T; Schattman, Glenn L; Rosenwaks, Zev

2017-09-01

To compare the oocyte and embryo yield associated with GnRH-agonist triggers vs. hCG triggers in cancer patients undergoing controlled ovarian stimulation (COS) for fertilization preservation. Retrospective cohort study. Academic center. Cancer patients undergoing COS with letrozole and gonadotropins or gonadotropin-only protocols for oocyte or embryo cryopreservation. Gonadotropin-releasing hormone agonist or hCG trigger. Number of metaphase II (MII) oocytes or two-pronuclei (2PN) embryos available for cryopreservation were primary outcomes. Separate multivariate linear regression models were used to assess the effect of trigger type on the primary outcomes, after controlling for confounders of interest. A total of 341 patients were included, 99 (29.0%) in the GnRH-agonist group and 242 (71%) in the hCG group. There was no difference in the baseline demographics of patients receiving GnRH-agonist or hCG triggers. Within the letrozole and gonadotropins group (n = 269), the number (mean ± SD, 11.8 ± 5.8 vs. 9.9 ± 6.0) and percentage of MII oocytes (89.6% vs. 73.0%) available for cryopreservation was higher with GnRH-agonist triggers compared with hCG triggers. Similar results were noted with GnRH-agonist triggers in the gonadotropin-only group (n = 72) (i.e., a higher number [13.3 ± 7.9 vs. 9.3 ± 6.0] and percentage of MII oocytes [85.7% vs. 72.8%] available for cryopreservation). Multivariate linear regression demonstrated approximately three more MII oocytes and 2PN embryos available for cryopreservation in the GnRH-agonist trigger group, irrespective of cancer and COS protocol type. Utilization of a GnRH-agonist trigger increases the number of MII oocytes and 2PN embryos available for cryopreservation in cancer patients undergoing COS for fertility preservation. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertility following CIDR based synchronization regimens in anoestrous Nili-Ravi buffaloes.

PubMed

Naseer, Z; Ahmad, E; Singh, J; Ahmad, N

2011-10-01

The objective of this study was to compare oestrus expression and fertility rate in used and new controlled internal drug releasing (CIDR) device treated anoestrous buffaloes. Furthermore, to determine the timing of ovulation, and fertility rate in estradiol benzoate (EB) and GnRH-administered CIDR-treated anoestrous Nili-Ravi buffaloes. In experiment 1, buffaloes received either a used CIDR (UCIDR, n = 35) or a new CIDR (NCIDR, n = 36) for 7 day and PGF2α on day 6. Oestrous expression was similar (p > 0.05) between UCIDR (88.5%) and NCIDR (96.6%) buffaloes. The pregnancy rate did not differ (p > 0.05) because of treatment (37.1% in UCIDR vs 36.6% in NCIDR). In experiment 2, buffaloes (n = 55) received CIDR device for 7 days and PGF2α, on day 6 and randomly assigned into three treatment groups: (i) CIDR-EB (n = 17) received EB on day 8, (ii) CIDR-GnRH (n = 18) received GnRH on day 9 and (iii) control (n = 20) received no further treatment. Mean interval from CIDR removal to ovulation in CIDR-EB, CIDR-GnRH and CIDR group were 61.3 ± 0.8, 64.9 ± 1.8 and 65.1 ± 16.7 h, respectively. However, the buffaloes in the CIDR-EB and CIDR-GnRH group had lesser variability in the timing of ovulation compared to control. The pregnancy rate of both CIDR-EB group (58%) and CIDR-GnRH group (61%) were tended to be higher (p < 0.1) than control (30%). In conclusion, compared to NCIDR devices, previously UCIDR devices are equally effective to induce oestrus in anoestrous buffaloes resulting optimal pregnancy rate. Administration of EB and GnRH after CIDR removal results in tighter synchrony (less variability) and improved fertility in anoestrous buffaloes. CIDR based synchronization regimens have great potential in fertility improvement in anoestrous buffaloes. © 2011 Blackwell Verlag GmbH.

Conformational space comparison of GnRH and lGnRH-III using molecular dynamics, cluster analysis and Monte Carlo thermodynamic integration.

PubMed

Watts, C R; Mezei, M; Murphy, R F; Lovas, S

2001-04-01

The conformational space available to GnRH and lGnRH-III was compared using 5.2 ns constant temperature and pressure molecular dynamics simulations with explicit TIP3P solvation and the AMBER v. 5.0 force field. Cluster analysis of both trajectories resulted in two groups of conformations. Results of free energy calculations, in agreement with previous experimental data, indicate that a conformation with a turn from residues 5 through 8 is preferred for GnRH in an aqueous environment. By contrast, a conformation with a helix from residues 2 through 7 with a bend from residues 6 through 10 is preferred for lGnRH-III in an aqueous environment. The side chains of His2 and Trp3 in lGnRH-III occupy different regions of phase space and participate in weakly polar interactions different from those in GnRH. The unique conformational properties of lGnRH-III may account for its specific anti cancer activity.

Effect of nano-hydroxyapatite on bone morphogenetic protein-2-induced hard tissue formation and dentin resorption on a dentin surface

NASA Astrophysics Data System (ADS)

Tamagawa, Hiroki; Tenkumo, Taichi; Sugaya, Tsutomu; Kawanami, Masamitsu

2012-12-01

AimThe purpose of this study was to evaluate the effects of the addition of nano-hydroxyapatite to a collagen membrane-carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) on hard tissue formation and dentin resorption on dentin surfaces in vivo. Materials and methodsNano-hydroxyapatite collagen composite (nHAC) membranes or collagen (C) membranes were each immersed in either 100 or 400 μg/ml rhBMP-2 and placed on dentin chips that were implanted into rat thigh muscle. The implants were analyzed at 2 or 4 weeks after surgery by histological observation and histomorphometric analysis. ResultsThe percentage of the hard tissue formed by each nHAC group was significantly higher than that formed by any of the C groups, except for that formed by the group loaded with 400 μg/ml rhBMP-2 at 4 weeks after implantation. No significant differences were observed in the percentage of dentin resorption between the nHAC groups and C groups at any stage or at any rhBMP-2 concentration. ConclusionThese findings showed that addition of nano-hydroxyapatite to a collagen membrane accelerated the formation of hard tissue induced by a low dose of rhBMP-2 on dentin surfaces at an early stage after implantation into rat thigh muscle, without increasing dentin resorption.

Dual suppression with oral contraceptive pills in GnRH antagonist cycles for patients with polycystic ovary syndrome undergoing intracytoplasmic sperm injection.

PubMed

Ozmen, B; Sükür, Y E; Seval, M M; Ateş, C; Atabekoğlu, C S; Sönmezer, M; Berker, B

2014-12-01

To evaluate the effects of a gonadotropin-releasing hormone (GnRH) antagonist protocol, with or without oral contraceptive pill (OCP) pretreatment, in patients with polycystic ovary syndrome (PCOS) undergoing intracytoplasmic sperm injection (ICSI). In this retrospective cohort study, 410 infertile patients with PCOS were assessed in their first ICSI cycles between January 2006 and June 2013. In Group A (n=208), patients underwent a long luteal GnRH agonist protocol, and in Groups B (n=143) and C (n=59), patients underwent a GnRH antagonist protocol. The patients in Group C also received OCPs containing 30mg of ethinyl oestradiol and 3mg of drospirenone prior to treatment. The main outcome measures were pregnancy and ovarian hyperstimulation syndrome (OHSS) rates. Demographic features, body mass index, duration of infertility, serum baseline hormone levels, cycle outcomes, multiple pregnancy rates, miscarriage rates, OHSS rates, total number of Grade A embryos and total number of transferred embryos were comparable between the groups. Clinical pregnancy rates were 27.4%, 26.6% and 23.7% in Groups A, B and C, respectively (p=0.853). OCP pretreatment was found to have no beneficial or adverse effects in patients with PCOS undergoing a GnRH antagonist protocol for ICSI, but can be used for cycle scheduling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Gonadotrophin-releasing hormone antagonists for assisted conception.

PubMed

Al-Inany, H G; Abou-Setta, A M; Aboulghar, M

2006-07-19

Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This has resulted in dramatic reduction in the duration of treatment cycle. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day six to seven of stimulation, or when the leading follicle is 14 to15 mm, until human chorionic gonadotrophin (HCG) administration and the single-dose protocol involves the single administration of 3 mg cetrorelix on day seven to eight of stimulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens. To evaluate the evidence regarding the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception. We searched Cochrane Menstrual Disorders and Subfertility Group's Specialised Register, MEDLINE and EMBASE databases from 1987 to February 2006, and handsearched bibliographies of relevant publications and reviews, and abstracts of scientific meetings. We also contacted manufacturers in the field. Randomized controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review. Two authors independently assessed trial quality and extracted data. If relevant data were missing or unclear, the authors have been consulted Twenty seven RCTs comparing the GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria. Clinical pregnancy rate was significantly lower in the antagonist group. (OR = 0.84, 95% CI = 0.72 - 0.97). The ongoing pregnancy/ live-birth rate showed the same significant lower pregnancy in the antagonist group (P = 0.03; OR 0.82, 95% CI 0.69 to 0.98).However, there was statistically significant reduction in incidence of severe OHSS with antagonist protocol. The relative risk ratio was (P = 0.01; RR 0.61, 95% CI 0.42 to 0.89). In addition, interventions to prevent OHSS (e.g. coasting, cycle cancellation) were administered more frequently in the agonist group (P = 0.03; OR 0.44, 95% CI 0.21 to 0.93). GnRH antagonist protocol is a short and simple protocol with good clinical outcome with significant reduction in incidence of severe ovarian hyperstimulation syndrome and amount of gonadotrophins but the lower pregnancy rate compared to the GnRH agonist long protocol necessitates counseling subfertile couples before recommending change from GnRH agonist to antagonist..

Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertension.

PubMed

Hermida, Ramón C; Ríos, María T; Crespo, Juan J; Moyá, Ana; Domínguez-Sardiña, Manuel; Otero, Alfonso; Sánchez, Juan J; Mojón, Artemio; Fernández, José R; Ayala, Diana E

2013-03-01

Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p < .001), resulting in significantly higher prevalence of non-dipping in these two treatment-time regimen groups (80.5% and 77.3%, respectively) than in the bedtime regimen (54.4%; p < .001 between groups). Additionally, the prevalence of the riser BP pattern, associated with highest CVD risk, was much greater, 31.0% and 29.8%, respectively, among patients of the upon-awakening and BID-treatment regimens, compared with the bedtime regimen (17.6%; p < .001 between groups). Patients of the bedtime regimen also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) as a result of a greater proportion of them showing complete control of asleep SBP and DBP means. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of blunted nighttime BP decline, i.e., lower prevalence of CVD risk markers, in RH patients ingesting the full daily dose of ≥1 hypertension medications at bedtime than in those ingesting all of them upon awakening or ≥1 of them as split doses BID. In RH, ingesting the same medications BID neither improves ambulatory BP control nor reduces the prevalence of non-dipping, and cannot be considered chronotherapy. Collectively, findings of this study indicate that a bedtime hypertension medication regimen, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of true RH and avoid treatment-induced nocturnal hypotension, should be the therapeutic scheme of choice for patients who, by conventional cuff methods (and in the absence of ABPM) and the morning-treatment regimen, have been mistakenly judged to be resistant to therapy.

The evolving science of detection of ‘blood doping’

PubMed Central

Lundby, Carsten; Robach, Paul; Saltin, Bengt

2012-01-01

Blood doping practices in sports have been around for at least half a century and will likely remain for several years to come. The main reason for the various forms of blood doping to be common is that they are easy to perform, and the effects on exercise performance are gigantic. Yet another reason for blood doping to be a popular illicit practice is that detection is difficult. For autologous blood transfusions, for example, no direct test exists, and the direct testing of misuse with recombinant human erythropoietin (rhEpo) has proven very difficult despite a test exists. Future blood doping practice will likely include the stabilization of the transcription factor hypoxia-inducible factor which leads to an increased endogenous erythropoietin synthesis. It seems unrealistic to develop specific test against such drugs (and the copies hereof originating from illegal laboratories). In an attempt to detect and limit blood doping, the World Anti-Doping Agency (WADA) has launched the Athlete Biological Passport where indirect markers for all types of blood doping are evaluated on an individual level. The approach seemed promising, but a recent publication demonstrates the system to be incapable of detecting even a single subject as ‘suspicious’ while treated with rhEpo for 10–12 weeks. Sad to say, the hope that the 2012 London Olympics should be cleaner in regard to blood doping seems faint. We propose that WADA strengthens the quality and capacities of the National Anti-Doping Agencies and that they work more efficiently with the international sports federations in an attempt to limit blood doping. PMID:22225538

Evaluation of a new automated instrument for pretransfusion testing.

PubMed

Morelati, F; Revelli, N; Maffei, L M; Poretti, M; Santoro, C; Parravicini, A; Rebulla, P; Cole, R; Sirchia, G

1998-10-01

A number of automated devices for pretransfusion testing have recently become available. This study evaluated a fully automated device based on column agglutination technology (AutoVue System, Ortho, Raritan, NJ). Some 6747 tests including forward and reverse ABO group, Rh type and phenotype, antibody screen, autocontrol, and crossmatch were performed on random samples from 1069 blood donors, 2063 patients, and 98 newborns and cord blood. Also tested were samples from 168 immunized patients and 53 donors expressing weak or variant A and D antigens. Test results and technician times required for their performance were compared with those obtained by standard methods (manual column agglutination technology, slide, semiautomatic handler). No erroneous conclusions were found in regard to the 5028 ABO group and Rh type or phenotype determinations carried out with the device. The device rejected 1.53 percent of tests for sample inadequacy. Of the remaining 18 tests with discrepant results found with the device and not confirmed with the standard methods, 6 gave such results because of mixed-field reactions, 10 gave negative results with A2 RBCs in reverse ABO grouping, and 2 gave very weak positive reactions in antibody screening and crossmatching. In the samples from immunized patients, the device missed one weak anti-K, whereas standard methods missed five weak antibodies. In addition, 48, 34, and 31 of the 53 weak or variant antigens were detected by the device, the slide method, and the semiautomated handler, respectively. Technician time with the standard methods was 1.6 to 7 times higher than that with the device. The technical performance of the device compared favorably with that of standard methods, with a number of advantages, including in particular the saving of technician time. Sample inadequacy was the most common cause of discrepancy, which suggests that standardization of sample collection can further improve the performance of the device.

[Resistant hypertension: An update].

PubMed

Renna, N F

2018-02-04

An estimated 10% to 20% of hypertensive patients could be considered resistant to treatment (RH). These are patients who are not controlled using three drugs, at the maximum tolerated doses, including a diuretic, as well as those with high blood pressure controlled using four or more drugs. The term is used to identify patients that might benefit from special diagnostic and/or therapeutic consideration. The term 'refractory hypertension' has recently been proposed as a novel phenotype of antihypertensive failure. It refers to patients whose blood pressure cannot be controlled with maximum treatment. The first studies of this phenotype indicate that it is rare and affects less than 5% of patients with RH. Adherence to or compliance with medical treatment is key to defining resistant hypertension. Closer attention has been paid to clinical and experimental research since the first scientific statement for the diagnosis, assessment and treatment of RH from the American Heart Association, and in the European guidelines, was published in 2008. This review will set out the concepts relating to prevalence, prognosis and compliance and cover the latest developments on this subject. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Influence of rhBMP-2 on Guided Bone Regeneration for Placement and Functional Loading of Dental Implants: A Radiographic and Histologic Study in Dogs.

PubMed

Ben Amara, Heithem; Lee, Jung-Won; Kim, Jung-Ju; Kang, Yun-Mi; Kang, Eun-Jung; Koo, Ki-Tae

Evidence on the outcomes of functional loading placed in recombinant human bone morphogenetic protein 2 (rhBMP-2)/acellular collagen sponge (ACS)-induced bone is lacking. The aim of this study was to verify whether guided bone regeneration (GBR) with rhBMP-2/ACS enhances regeneration of missing bone and osseointegration of dental implants subject to functional loading. Two bilateral standardized large saddle-type defects (≈10 × 10 × 6 mm) were surgically created in each mandible of seven beagle dogs 2 months after tooth extraction. Defects were immediately reconstructed randomly using rhBMP-2 (O-BMP or InFuse) soaked in ACS, deproteinized bovine bone mineral (DBBM) granules, or ACS alone as surgical control and subsequently covered with collagen membrane. Screw-type sand-blasted, acid-etched dental implants were placed 3 months later into the reconstructed defects and into adjacent bone. Osseointegration was allowed to progress for 3 months before functional loading of 3 months until sacrifice. Significantly more bone fill was radiographically observed for GBR with rhBMP-2/ACS (O-BMP: 92.5%, InFuse: 79%) in comparison to the DBBM (52%) and ACS alone groups (56.6%). Osseointegration was achieved and maintained in all experimental defects challenged by prostheses-driven functional load. The bone density ranged from 37.49% in the ACS group to 64.9% in the rhBMP-2/ACS (InFuse) group with no significance. The highest mean percentage of BIC was found in rhBMP-2/ACS (InFuse: 52.98%) with no statistical difference. Crestal bone resorption was observed around implants placed in reconstructed areas without any significant difference. GBR with rhBMP-2/ACS provided the greatest bone fill among the three treatment procedures. GBR with rhBMP-2/ACS showed efficacy for placement, osseointegration, and functional loading of titanium implants in alveolar ridge defects.

Mentoring Interventions and the Impact of Protective Assets on the Reproductive Health of Adolescent Girls and Young Women.

PubMed

Plourde, Kate F; Ippoliti, Nicole B; Nanda, Geeta; McCarraher, Donna R

2017-08-01

Adolescent girls and young women (AGYW) are disproportionately affected by HIV and AIDS and other negative reproductive health (RH) outcomes. Emerging evidence suggests that programs to build AGYW's assets can help reduce their vulnerability to poor RH. Mentoring interventions have demonstrated a positive impact on a variety of youth development outcomes, including the protective assets needed to circumvent poor RH outcomes. The purpose of this review was to understand the types of mentoring programs for AGYW that have demonstrated effectiveness in improving protective assets, and/or, RH knowledge, intentions, behaviors, or outcomes themselves. Interventions were identified through an electronic search of the peer-reviewed and the gray literature. Studies were excluded in stages based on reviews of titles, abstracts, and full text. A review of 491 publications yielded a total of 19 articles that were included in the final review. The majority of the publications examined the impact of the one-to-one mentoring model in the United States. However, a good proportion examined the impact of both one-on-one and group-based interventions globally. The few interventions that followed a group-based model demonstrated more promise; evaluations of this model demonstrated a positive impact on RH knowledge and behavior, academic achievement, financial behavior, and social networks, as well as reductions in the experience of violence. Group-based mentoring programs demonstrated the most promise in building AGYW's protective assets and improving their RH outcomes. The most successful interventions consisted of multiple components, including mentoring, that sought to directly improve AGYW's protective assets and met with more frequency over a longer duration. Despite the promising evidence, more research is needed to better understand the relationship between assets and RH; the characteristics of successful mentoring programs; and the influence mentoring alone has on RH outcomes, versus mentoring as part of a larger RH program. Copyright © 2017 Society for Adolescent Health and Medicine. All rights reserved.

Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.

PubMed

Altuntas, Yuksel; Bilir, Muammer; Ucak, Sema; Gundogdu, Sadi

2005-04-01

Reactive hypoglycemia (RH), which is a postprandial hypoglycemic state, occurs within 2-5 h after food intake. It is classified as idiopathic, alimentary, or diabetic reactive hypoglycemia. We studied the incidence of reactive hypoglycemia and looked for any correlations between it and the presence of insulin sensitivity and/or beta cell function in young lean polycystic ovary syndrome (PCOS) patients. This study was designed as a cross-sectional study in 64 lean young women with PCOS (BMI < or = 25 kg/m2). Various indices of insulin sensitivity and beta cell function derived from the oral glucose tolerance test (OGTT) results were used. We found the rate of RH to be 50% in lean young women with PCOS. DHEA-S and PRL levels were found to be lower in subjects with RH (P < 0.05 and P > 0.05, respectively). Beta cell function indices such as the insulinogenic index (at 120 min), CIR (at 120 min) and HOMA beta cell index were found to be insignificantly higher in the RH group than the nonreactive hypoglycemia (NRH) group. The 4 h glucose level, but not the 3 h glucose level, was significantly correlated with insulin resistance indices, such as fasting insulin level, HOMA-IR, Quicky index, and FIRI in the RH group. Significantly decreased DHEA-S levels were an interesting finding. In conclusion, there is an urgent need to investigate RH in lean young women with PCOS. Our results indicate that more definite insulin resistance occurs in subjects with RH in the fourth hour of the OGTT than those with RH in the third hour. In addition, RH in the fourth hour together with a low DHEA-S level may be predictive of future diabetes in young women with PCOS even when they are not obese.

Effect of rhBMP-2 on tibial plateau fractures in a canine model.

PubMed

Schaefer, Susan L; Lu, Yan; Seeherman, Howard; Li, X Jian; Lopez, Mandi J; Markel, Mark D

2009-04-01

This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model.

[Clinical outcomes and economic analysis of two ovulation induction protocols in patients undergoing repeated IVF/ICSI cycles].

PubMed

Chen, Xiao; Geng, Ling; Li, Hong

2014-04-01

To compare the clinical outcomes and cost-effectiveness of luteal phase down-regulation with gonadotrophin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol in patients undergoing repeated in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI) cycles. A retrospective analysis of clinical outcomes and costs was conducted among 198 patients undergoing repeated IVF-ICSI cycles, including 109 receiving luteal phase down-regulation with GnRH agonist protocol (group A) and 89 receiving GnRH antagonist protocol (group B). The numbers of oocytes retrieved and good embryos, clinical pregnancy rate, abortion rate, the live birth rate, mean total cost, and the cost-effective ratio were compared between the two groups. In patients undergoing repeated IVF-ICSI cycles, the two protocols produced no significant differences in the number of good embryos, clinical pregnancy rate, abortion rate, or twin pregnancy rate. Compared with group B, group A had better clinical outcomes though this difference was not statistically significant. The number of retrieved oocytes was significantly greater and live birth rate significantly higher in group A than in group B (9.13=4.98 vs 7.11=4.74, and 20.2% vs 9.0%, respectively). Compared with group B, group A had higher mean total cost per cycle but lower costs for each oocyte retrieved (2729.11 vs 3038.60 RMB yuan), each good embryo (8867.19 vs 9644.85 RMB yuan), each clinical pregnancy (77598.06 vs 96139.85 RMB yuan). For patients undergoing repeated IVF/ICSI cycle, luteal phase down-regulation with GnRH agonist protocol produces good clinical outcomes with also good cost-effectiveness in spite an unsatisfactory ovarian reserve.

In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, A.M.; Zsebo, K.M.; Inoue, H.

1987-04-01

Osmotic pumps containing Escherichia coli-derived recombinant human granulocyte colony-stimulating factor (rhG-CSF) were attached to indwelling jugular vein catheters and implanted subcutaneously into Golden Syrian hamsters. Within 3 days, peripheral granulocyte counts had increased > 10-fold with a concomitant 4-fold increase in total leukocytes. Microscopic examination of Wright-Giemsa-stained blood smears from rhG-CSF hamsters showed that only the neutrophil subpopulation of granulocytes had increased. After subcutaneous injection at /sup 35/S-labeled rhG-CSF doses of up to 10 ..mu..g x kg/sup -1/ x day/sup -1/ only granulocyte counts were affected. However, at higher dose levels, a transient thrombocytopenia was noted. Erythrocyte and lymphocyte/monocyte countsmore » remained unaffected by rhG-CSF over the entire dose range studied. Total leukocyte counts increased 3-fold within 12 hr after a single s.c. injection of rhG-CSF. This early effect was associated with an increase in the total number of colony-forming cells and the percent of active cycling cells in the marrow. A sustained elevation of peripheral leukocyte and marrow progenitor counts was observed following seven daily s.c. injections of rhG-CSF. The ability of rhG-CSF to increase the production and release of granulocytes from the marrow may underlie the beneficial effect it produced on the restoration of peripheral leukocyte counts in hamsters made leukopenic by treatment with 5-fluorouracil.« less

Mutation of Surface Residues to Promote Crystallization of Activated Factor XI as a Complex with Benzamidine: an Essential Step for the Iterative Structure-Based Design of Factor XI Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin,L.; Pandey, P.; Babine, R.

Activated factor XI (FXIa) is a key enzyme in the amplification phase of the blood-coagulation cascade. Thus, a selective FXIa inhibitor may have lesser bleeding liabilities and provide a safe alternative for antithrombosis therapy to available drugs on the market. In a previous report, the crystal structures of the catalytic domain of FXIa (rhFXI370-607) in complex with various ecotin mutants have been described [Jin et al. (2005), Journal of Biological Chemistry 280, 4704-4712]. However, ecotin forms a matrix-like interaction with rhFXI370-607 and is impossible to displace with small-molecule inhibitors; ecotin crystals are therefore not suitable for iterative structure-based ligand design.more » In addition, rhFXI370-607 did not crystallize in the presence of small-molecule ligands. In order to obtain the crystal structure of rhFXI370-607 with a weak small-molecule ligand, namely benzamidine, several rounds of surface-residue mutation were implemented to promote crystal formation of rhFXI370-607. A quadruple mutant of rhFXI370-607 (rhFXI370-607-S434A, T475A, C482S, K437A) readily crystallized in the presence of benzamidine. The benzamidine in the preformed crystals was easily exchanged with other FXIa small-molecule inhibitors. These crystals have facilitated the structure-based design of small-molecule FXIa inhibitors.« less

Maternal red blood cell alloimmunisation in south western Uganda.

PubMed

Natukunda, B; Mugyenyi, G; Brand, A; Schonewille, H

2011-08-01

To identify the frequency and nature of maternal red blood cell (RBC) alloimmunisation in Uganda and to determine the prevalence of RhD negativity and the rate of RBC alloimmunisation in Ugandan pregnant women. Haemolytic disease of the foetus and newborn (HDFN) results from maternal alloimmunisation following exposure to allogeneic RBCs during pregnancy or blood transfusion. The prevalence of maternal RBC alloimmunisation in Ugandans is not known. Pregnant women at Mbarara Hospital, South Western Uganda, were investigated in a cross-sectional study. Demographics, transfusion and obstetric histories were recorded. Maternal RBC alloimmunisation was demonstrated using immunohaematological techniques. A total of 2001 pregnant women were recruited; 3.6% of them being RhD negative. Forty-five women (2.2%; 95% CI: 1.6-2.9) were found to be alloimmunised to RBC antigens. There were 38 RBC alloantibodies of known specificity including anti-S, 12; anti-M, 11; anti-Le(a) , 6; anti-D, 4 and 1 each of anti-K, anti-Fy(b) , anti-Jk(a) , anti-Lu(a) and anti-Kp(a) . In two women (4.4%), there were antibody combinations (anti-M+S and anti-K+Kp(a) ). Obstetric history, gestational age and previous immunising events were not significantly associated with the rate of alloimmunisation. This study revealed a maternal RBC alloimmunisation rate of 2.2% which was comparable with findings from a Zimbabwean study where the prevalence was 1.7%. Given the 6·0% prevalence of anti-D among RhD-negative women in our study and the high immunogenicity of the D antigen, programmes for preventing anti-D alloimmunisation and HDFN in Uganda should be considered seriously. © 2011 The Authors. Transfusion Medicine © 2011 British Blood Transfusion Society.

Growth and maturational changes in dense fibrous connective tissue following 14 days of rhGH supplementation in the dwarf rat

NASA Technical Reports Server (NTRS)

Kyparos, Antonios; Orth, Michael W.; Vailas, Arthur C.; Martinez, Daniel A.

2002-01-01

The purpose of this study was to investigate the impact of recombinant human growth hormone (rhGH) on patella tendon (PT), medial collateral ligament (MCL), and lateral collateral ligament (LCL) on collagen growth and maturational changes in dwarf GH-deficient rats. Twenty male Lewis mutant dwarf rats, 37 days of age, were randomly assigned to Dwarf + rhGH (n = 10) and Dwarf + vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt twice daily for 14 days. rhGH administration stimulated dense fibrous connective tissue growth, as demonstrated by significant increases in hydroxyproline specific activity and significant decreases in the non-reducible hydroxylysylpyridinoline (HP) collagen cross-link contents. The increase in the accumulation of newly accreted collagen was 114, 67, and 117% for PT, MCL, and LCL, respectively, in 72 h. These findings suggest that a short course rhGH treatment can affect the rate of new collagen production. However, the maturation of the tendon and ligament tissues decreased 18-25% during the rapid accumulation of de novo collagen. We conclude that acute rhGH administration in a dwarf rat can up-regulate new collagen accretion in dense fibrous connective tissues, while causing a reduction in collagen maturation. Copyright 2002 Elsevier Science Ltd.

A dual task priming investigation of right hemisphere inhibition for people with left hemisphere lesions

PubMed Central

2012-01-01

Background During normal semantic processing, the left hemisphere (LH) is suggested to restrict right hemisphere (RH) performance via interhemispheric suppression. However, a lesion in the LH or the use of concurrent tasks to overload the LH's attentional resource balance has been reported to result in RH disinhibition with subsequent improvements in RH performance. The current study examines variations in RH semantic processing in the context of unilateral LH lesions and the manipulation of the interhemispheric processing resource balance, in order to explore the relevance of RH disinhibition to hemispheric contributions to semantic processing following a unilateral LH lesion. Methods RH disinhibition was examined for nine participants with a single LH lesion and 13 matched controls using the dual task paradigm. Hemispheric performance on a divided visual field lexical decision semantic priming task was compared over three verbal memory load conditions, of zero-, two- and six-words. Related stimuli consisted of categorically related, associatively related, and categorically and associatively related prime-target pairs. Response time and accuracy data were recorded and analyzed using linear mixed model analysis, and planned contrasts were performed to compare priming effects in both visual fields, for each of the memory load conditions. Results Control participants exhibited significant bilateral visual field priming for all related conditions (p < .05), and a LH advantage over all three memory load conditions. Participants with LH lesions exhibited an improvement in RH priming performance as memory load increased, with priming for the categorically related condition occurring only in the 2- and 6-word memory conditions. RH disinhibition was also reflected for the LH damage (LHD) group by the removal of the LH performance advantage following the introduction of the memory load conditions. Conclusions The results from the control group are consistent with suggestions of an age related hemispheric asymmetry reduction and indicate that in healthy aging compensatory bilateral activation may reduce the impact of inhibition. In comparison, the results for the LHD group indicate that following a LH lesion RH semantic processing can be manipulated and enhanced by the introduction of a verbal memory task designed to engage LH resources and allow disinhibition of RH processing. PMID:22429687

Apheresis product identification in the transplant center: development of point-of-care protocols for extended blood typing of stem cell apheresis products.

PubMed

Cummerow, C; Schwind, P; Spicher, M; Spohn, G; Geisen, C; Seifried, E; Bönig, H

2012-06-01

Transfusion of the 'wrong' stem cell product would almost inevitably be lethal, yet assays to confirm the contents of the product bag, except by checking labels and paperwork, are lacking. To increase the likelihood that a product mix-up would be detected in the transplant center, we developed a simple protocol for extended blood typing and hence, for confirmation of donor/product identity, on a tube segment. Apheresis samples were applied, directly or after erythrocyte enrichment, to commercially available blood typing assays, including lateral flow cards and gel agglutination cards. Without sample modification, low hematocrit and high leukocyte count obviated definitive blood typing. Using the most simple erythrocyte enrichment protocol, that is, centrifugation, reliable blood group analysis became possible with either assay. Other, more cumbersome pre-analytical protocols were also successful but provided no advantage. The preferred method was validated on 100 samples; ABD was correctly identified in 100% of cases. Of the other Rh Ags, all except two 'small e', in both cases in heterozygous individuals, were detected; there were no false positives. A simple, inexpensive point-of-care assay for extended blood typing of apheresis products is available, which can reduce the fatal risk of administering the wrong stem cell product.

Reverse the diastereoselectivity of the Rh(I)-catalyzed Pauson-Khand cycloaddition.

PubMed

Turlington, Mark; Pu, Lin

2011-08-19

It is discovered that the diastereoselectivity of the Rh(I)-catalyzed Pauson-Khand cycloaddition of chiral enynes can be reversed to generate the trans diastereomer as the major product in the absence of a chelate phosphine ligand when the substrate contains an appropriate functional group capable of chelate coordination to the Rh(I) center. This expands the application of the Rh(I)-based catalytic processes to prepare both the cis and trans stereoisomers. © 2011 American Chemical Society

Experimental infection with the Toxoplasma gondii ME-49 strain in the Brazilian BR-1 mini pig is a suitable animal model for human toxoplasmosis.

PubMed

Miranda, Farlen José Bebber; Souza, Diogo Benchimol de; Frazão-Teixeira, Edwards; Oliveira, Fábio Conceição de; Melo, João Cardoso de; Mariano, Carlos Magno Anselmo; Albernaz, Antonio Peixoto; Carvalho, Eulógio Carlos Queiróz de; Oliveira, Francisco Carlos Rodrigues de; Souza, Wanderley de; DaMatta, Renato Augusto

2015-02-01

Toxoplasma gondii causes toxoplasmosis, a worldwide disease. Experimentation with pigs is necessary for the development of new therapeutic approaches to human diseases. BR-1 mini pigs were intramuscularly infected with T. gondii with tachyzoites (RH strain) or orally infected with cysts (ME-49 strain). Haematology and serum biochemistry were analysed and buffy coat cells were inoculated in mice to determine tachyzoite circulation. No alterations were observed in erythrocyte and platelet values; however, band neutrophils increased seven days after infection with ME-49. Serology of the mice inoculated with pig blood leucocytes revealed circulating ME-49 or RH strain tachyzoites in the pigs' peripheral blood at two and seven or nine days post-infection. The tachyzoites were also directly observed in blood smears from the infected pigs outside and inside leucocytes for longer periods. Alanine-aminotransferase was high at days 21 and 32 in the RH infected pigs. After 90 days, the pigs were euthanised and their tissue samples were processed and inoculated into mice. The mice serology revealed the presence of parasites in the hearts, ileums and mesenteric lymph nodes of the pigs. Additionally, cysts in the mice were only observed after pig heart tissue inoculation. The infected pigs presented similar human outcomes with relatively low pathogenicity and the BR-1 mini pig model infected with ME-49 is suitable to monitor experimental toxoplasmosis.

Experimental infection with the Toxoplasma gondii ME-49 strain in the Brazilian BR-1 mini pig is a suitable animal model for human toxoplasmosis

PubMed Central

Miranda, Farlen José Bebber; de Souza, Diogo Benchimol; Frazão-Teixeira, Edwards; de Oliveira, Fábio Conceição; de Melo, João Cardoso; Mariano, Carlos Magno Anselmo; Albernaz, Antonio Peixoto; de Carvalho, Eulógio Carlos Queiróz; de Oliveira, Francisco Carlos Rodrigues; de Souza, Wanderley; DaMatta, Renato Augusto

2015-01-01

Toxoplasma gondii causes toxoplasmosis, a worldwide disease. Experimentation with pigs is necessary for the development of new therapeutic approaches to human diseases. BR-1 mini pigs were intramuscularly infected with T. gondii with tachyzoites (RH strain) or orally infected with cysts (ME-49 strain). Haematology and serum biochemistry were analysed and buffy coat cells were inoculated in mice to determine tachyzoite circulation. No alterations were observed in erythrocyte and platelet values; however, band neutrophils increased seven days after infection with ME-49. Serology of the mice inoculated with pig blood leucocytes revealed circulating ME-49 or RH strain tachyzoites in the pigs' peripheral blood at two and seven or nine days post-infection. The tachyzoites were also directly observed in blood smears from the infected pigs outside and inside leucocytes for longer periods. Alanine-aminotransferase was high at days 21 and 32 in the RH infected pigs. After 90 days, the pigs were euthanised and their tissue samples were processed and inoculated into mice. The mice serology revealed the presence of parasites in the hearts, ileums and mesenteric lymph nodes of the pigs. Additionally, cysts in the mice were only observed after pig heart tissue inoculation. The infected pigs presented similar human outcomes with relatively low pathogenicity and the BR-1 mini pig model infected with ME-49 is suitable to monitor experimental toxoplasmosis. PMID:25742268

Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease

PubMed Central

Nakagawa, Naoki; Gomez, Ivan G.; Johnson, Bryce G.; Kameoka, Sei; Jack, Richard M.; Lupher, Mark L.; Gharib, Sina A.; Duffield, Jeremy S.

2016-01-01

Pentraxin-2 (PTX-2), also known as serum amyloid P component (SAP/APCS), is a constitutive, antiinflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Here we show that recombinant human PTX-2 (rhPTX-2) retards progression of chronic kidney disease in Col4a3 mutant mice with Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously delivered rhPTX-2 was detected in macrophages but also in tubular epithelial cells, where it counteracted macrophage activation and was cytoprotective for the epithelium. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun along with its activator protein–1 (AP-1) binding partners as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun and AP-1 activity, and reduces expression of AP-1–dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting. PMID:27942582

A Critical Point of Male Gonad Development: Neuroendocrine Correlates of Accelerated Testicular Growth in Rats during Early Life

PubMed Central

Dygalo, Nikolay N.; Shemenkova, Tatjana V.; Kalinina, Tatjana S.; Shishkina, Galina T.

2014-01-01

Testis growth during early life is important for future male fertility and shows acceleration during the first months of life in humans. This acceleration coincides with the peak in gonadotropic hormones in the blood, while the role of hypothalamic factors remains vague. Using neonatal rats to assess this issue, we found that day 9 of life is likely critical for testis development in rats. Before this day, testicular growth was proportional to body weight gain, but after that the testes showed accelerated growth. Hypothalamic kisspeptin and its receptor mRNA levels begin to elevate 2 days later, at day 11. A significant increase in the mRNA levels for gonadotropin-releasing hormone (GnRH) receptors in the hypothalamus between days 5 and 7 was followed by a 3-fold decrease in GnRH mRNA levels in this brain region during the next 2 days. Starting from day 9, hypothalamic GnRH mRNA levels increased significantly and positively correlated with accelerated testicular growth. Triptorelin, an agonist of GnRH, at a dose that had no effect on testicular growth during “proportional” period, increased testis weights during the period of accelerated growth. The insensitivity of testicular growth to GnRH during “proportional” period was supported by inability of a 2.5-fold siRNA knockdown of GnRH expression in the hypothalamus of the 7-day-old animals to produce any effect on their testis weights. GnRH receptor blockade with cetrorelix was also without effect on testis weights during “proportional” period but the same doses of this GnRH antagonist significantly inhibited “accelerated” testicular growth. GnRH receptor mRNA levels in the pituitary as well as plasma LH concentrations were higher during “accelerated” period of testicular growth than during “proportional” period. In general, our data defined two distinct periods in rat testicular development that are primarily characterized by different responses to GnRH signaling. PMID:24695464

Mobilization of primitive and committed hematopoietic progenitors in nonhuman primates treated with defibrotide and recombinant human granulocyte colony-stimulating factor.

PubMed

Carlo-Stella, Carmelo; Di Nicola, Massimo; Longoni, Paolo; Milani, Raffaella; Milanesi, Marco; Guidetti, Anna; Haanstra, Krista; Jonker, Margaret; Cleris, Loredana; Magni, Michele; Formelli, Franca; Gianni, Alesssandro M

2004-01-01

The aim of this study was to evaluate the capacity of defibrotide in enhancing cytokine-induced hematopoietic mobilization in rhesus monkeys. Animals received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 100 microg/kg/day SC for 5 days) and, after a 4- to 6-week washout period, were remobilized with defibrotide (15 mg/kg/hour continuous intravenous for 5 days) plus rhG-CSF. Hematopoietic mobilization was evaluated by complete blood counts, differential counts, as well as frequency and absolute numbers of colony-forming cells (CFCs), high-proliferative potential CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). Compared to baseline values, rhG-CSF increased circulating CFCs, HPP-CFCs, and LTC-ICs by 158-, 125-, and 67-fold, respectively; the same figures for defibrotide/rhG-CSF were 299-, 1452-, and 295-fold, respectively. Defibrotide/rhG-CSF treatment compared to rhG-CSF alone increased CFCs, HPP-CFCs, and LTC-ICs by 1.4- (35,089 vs 25,825, p< or =0.02), 6- (4358 vs 748, p< or =0.02), and 5-fold (884 vs 168, p< or =0.04), respectively. We then evaluated the effects of a 2-day defibrotide treatment associated with a 5-day rhG-CSF treatment. Compared to rhG-CSF, defibrotide/rhG-CSF increased the mobilization of CFCs, HPP-CFCs, and LTC-ICs by 2- (31,128 vs 15,527, p< or =0.05), 8- (5361 vs 660, p< or =0.01), and 8-fold (954 vs 119, p< or =0.01), respectively. Our data demonstrate that in nonhuman primates: 1) defibrotide enhances rhG-CSF-elicited mobilization of primitive and committed progenitors; and 2) a 2-day defibrotide injection is as effective as a 5-day injection.

Evaluation of rhBMP-2/collagen/TCP-HA bone graft with and without bone marrow cells in the canine femoral multi defect model.

PubMed

Luangphakdy, V; Shinohara, K; Pan, H; Boehm, C; Samaranska, A; Muschler, G F

2015-01-12

Recombinant human bone morphogenetic protein-2, when applied to an absorbable type 1 bovine collagen sponge (rhBMP-2/ACS) is an effective therapy in many bone grafting settings. Bone marrow aspirate (BMA) has also been used as a source of transplantable osteogenic connective tissue progenitors. This study was designed to characterize the performance of a scaffold comprising rhBMP-2/ACS in which the sponge wraps around tri-calcium phosphate hydroxyapatite granules (rhBMP-2/ACS/TCP-HA) and to test the hypothesis that addition of BMA will improve the performance of this construct in the Canine Femoral Multi Defect Model. In each subject, two sites were grafted with rhBMP-2/ACS/TCP-HA scaffold loaded with BMA clot and two other sites with rhBMP-2/ACS/TCP-HA scaffold loaded with wound blood (WB). After correction for unresorbed TCP-HA granules, sites grafted with rhBMP-2/ACS/TCP-HA+BMA and rhBMP-2/ACS/TCP-HA+WB were similar, with mean percent bone volumes of 10.9 %±1.2 and 11.2 %±1.2, respectively. No differences were seen in quantitative histomorphometry. While bone formation using both constructs was robust, this study did not support the hypothesis that the addition of unprocessed bone marrow aspirate clot improved bone regeneration in a site engrafted with rhBMP-2/ACS/TCP-HA+BMA. In contrast to prior studies using this model, new bone formation was greater at the center of the defect where TCP-HA was distributed. This finding suggests a potential synergy between rhBMP-2 and the centrally placed ceramic and cellular components of the graft construct. Further optimization may also require more uniform distribution of TCP-HA, alternative cell delivery strategies, and a more rigorous large animal segmental defect model.

Rectal hyposensitivity and functional anorectal outlet obstruction are common entities in patients with functional constipation but are not significantly associated

PubMed Central

Lee, Tae Hee; Hong, Su Jin; Jeon, Seong Ran; Kwon, Soon Ha; Kim, Wan Jung; Kim, Hyun Gun; Cho, Won Young; Cho, Joo Young; Kim, Jin-Oh; Lee, Ji Sung

2013-01-01

Background/Aims The causes of functional anorectal outlet obstruction (outlet obstruction) include functional defecation disorder (FDD), rectocele, and rectal intussusception (RI). It is unclear whether outlet obstruction is associated with rectal hyposensitivity (RH) in patients with functional constipation (FC). The aim of this study was to determine the association between RH and outlet obstruction in patients with FC. Methods This was a retrospective study using a prospectively collected constipation database, and the population comprised 107 patients with FC (100 females; median age, 49 years). We performed anorectal manometry, defecography, rectal barostat, and at least two tests (balloon expulsion test, electromyography, or colon transit time study). RH was defined as one or more sensory threshold pressures raised beyond the normal range on rectal barostat. We investigated the association between the presence of RH and an outlet obstruction such as large rectocele (> 2 cm in size), RI, or FDD. Results Forty patients (37.4%) had RH. No significant difference was observed in RH between patients with small and large rectoceles (22 [44.9%] vs. 18 [31%], respectively; p = 0.140). No significant difference was observed in RH between the non-RI and RI groups (36 [36.7%] vs. 4 [30.8%], respectively; p = 0.599). Furthermore, no significant difference in RH was observed between the non-FDD and FDD groups (19 [35.8%] vs. 21 [38.9%], respectively; p = 0.745). Conclusions RH and outlet obstruction are common entities but appear not to be significantly associated. PMID:23345997

Hyperbilirubinemia in Neonates: Types, Causes, Clinical Examinations, Preventive Measures and Treatments: A Narrative Review Article

PubMed Central

ULLAH, Sana; RAHMAN, Khaista; HEDAYATI, Mehdi

2016-01-01

Background: Hyperbilirubinemia, or jaundice, is a life threatening disorder in newborns. It is a multifactorial disorder with many symptoms. Generally, the physiological jaundice is the most prevalent type however in some regions pathological jaundice is also common. This review article focuses on a brief introduction to jaundice, its types and causes, measuring the bilirubin level, clinical approaches towards hyperbilirubinemia, different precautionary measures for the parents of babies suffering from hyperbilirubinemia and different remedial therapeutic measures for its treatment. Methods: The main databases including Scopus, Pubmed, MEDLINE, Google scholar and Science Direct were researched to obtain the original papers related to the newborns’ hyperbilirubinemia. The main terms used to literature search were “newborns’ hyperbilirubinemia”, “newborns’ jaundice”, “Physiological Jaundice” and “Patholigical Jaundice”. The timeframe included the obtained articles was from 1952 to 2015. Results: Neonatal jaundice due to breast milk feeding is also sometimes observed. Hemolytic jaundice occurs because of the incompatibility of blood groups with ABO and Rh factors, when the fetus and mother blood groups are not compatible and the fetus blood crosses the barrier of the umbilical cord before birth causing fetus blood hemolysis owing to severe immune response. Conclusion: Jaundice is easily diagnosable however require quick and on the spot treatment. If not treated properly, it leads to many complications. Currently the treatment options for jaundice include photo therapy, chemotherapy, and vaccinations. PMID:27398328

Effects of ractopamine hydrochloride and dietary protein content on performance, carcass traits and meat quality of Nellore bulls.

PubMed

Cônsolo, N R B; Mesquita, B S; Rodriguez, F D; Rizzi, V G; Silva, L F P

2016-03-01

Ractopamine hydrochloride (RH) alters protein metabolism and improves growth performance in Bos taurus cattle with high carcass fat. Our objective was to evaluate the effects of RH, dietary CP and RH×CP interaction on performance, blood metabolites, carcass characteristics and meat quality of young Nellore bulls. A total of 48 bulls were randomly assigned to four treatments in a 2×2 factorial arrangement. The factors were two levels of dietary CP (100% and 120% of metabolizable protein requirement, defined as CP100 and CP120, respectively), and two levels of RH (0 and 300 mg/animal·per day). Treated animal received RH for the final 35 days before slaughter. Animals were weighed at the beginning of the feedlot period (day 63), at the beginning of ractopamine supplementation (day 0), after 18 days of supplementation (day 18) and before slaughter (day 34). Animals were slaughtered and hot carcass weights recorded. After chilling, carcass data was collected and longissimus samples were obtained for determination of meat quality. The 9-11th rib section was removed for carcass composition analysis. Supplementation with RH increased ADG independently of dietary CP. There was a RH×CP interaction on dry matter intake (DMI), where RH reduced DMI at CP120, with no effect at CP100. Ractopamine improved feed efficiency, without RH×CP interaction. Ractopamine had no effect on plasma creatinine and urea concentration. Greater dietary CP tended to increase blood urea, and there was a RH×CP interaction for plasma total protein. Ractopamine supplementation increased plasma total protein at CP120, and had no effect at CP100. Ractopamine also decreased plasma glucose concentration at CP100, but had no effect at CP120. Ractopamine increased alkaline phosphatase activity at CP120 and had no effect at CP100. There was a tendency for RH to increase longissimus muscle area, independently of dietary CP. Ractopamine did not alter fat thickness; however, fat thickness was reduced by greater CP in the diet. Supplementation with RH decreased meat shear force, but only at day 0 of aging, having no effect after 7, 14 or 21 days. Greater dietary protein increased meat shear force after 0 and 7 days of aging, with no effect after 14 or 21 days. These results demonstrate for the first time the efficacy of ractopamine supplementation to improve gain and feed efficiency of intact Bos indicus males, with relatively low carcass fat content. Ractopamine effects were not further improved by increasing dietary protein content above requirements.

(+)-Chlorido[(1,2,3,4-η;κP 2′)-2′-diphenyl­phosphanyl-2-diphenyl­phosphoryl-1,1′-binaphth­yl]rhodium(I) methanol monosolvate

PubMed Central

Meissner, Antje; Selle, Carmen; Drexler, Hans-Joachim; Heller, Detlef

2012-01-01

In the title complex, [RhCl(C44H32OP2)]·CH3OH, the RhI ion is coordinated by a naphthyl group of a partially oxidized 2,2′-bis­(diphenyl­phosphan­yl)-1,1′-binaphthyl (BINAP) ligand in a η4 mode, one P atom of the diphenyl­phosphanyl group and one Cl atom. The P=O group does not inter­act with the RhI ion but accepts an O—H⋯O hydrogen bond from the methanol solvent mol­ecule. PMID:22412414

Determination of boron in blood, urine and bone by electrothermal atomic absorption spectrometry using zirconium and citric acid as modifiers

NASA Astrophysics Data System (ADS)

Burguera, Marcela; Burguera, José Luis; Rondón, Carlos; Carrero, Pablo

2001-10-01

A comparative study of various potential chemical modifiers (Au, Ba, Be, Ca, Cr, Ir, La, Lu, Mg, Ni, Pd, Pt, Rh, Ru, Sr, V, W, and Zr), and different 'coating' treatments (Zr, W, and W+Rh) of the pyrolytic graphite platform of a longitudinally heated graphite tube atomizer for thermal stabilization and determination of boron was undertaken. The use of Au, Ba, Be, Cr, Ir, Pt, Rh, Ru, Sr and V as modifiers, and of W+Rh coating produced erratic, and noisy signals, while the addition of La, Ni and Pd as modifiers, and the W coating had positive effects, but with too high background absorption signals, rendering their use unsuitable for boron determination even in aqueous solutions. The atomic absorption signal for boron was increased and stabilized when the platform was coated with Zr, and by the addition of Ca, Mg, Lu, W or Zr as modifiers. Only the addition of 10 μg of Zr as a modifier onto Zr-treated platforms allowed the use of a higher pyrolysis temperature without analyte losses. The memory effect was minimized by incorporating a cleaning step with 10 μl of 50 g l -1 NH 4F HF after every three boron measurements. The addition of 10 μl of 15 g l -1 citric acid together with Zr onto Zr-treated platforms significantly improved the characteristic mass to m0=282 pg, which is adequate for biological samples such as urine and bone, although the sensitivity was still inadequate for the determination of boron in blood of subjects without supplementary diet. Under optimized conditions, the detection limit (3σ) was 60 μg l -1. The amount of boron found in whole blood, urine and femur head samples from patients with osteoporosis was in agreement with values previously reported in the literature.

Effects and mechanism of recombinant human erythropoietin on the growth of human breast cancer MDA-MB-231 cells in nude mice.

PubMed

Jin, Wen; Lin, Zhiwu; Zhang, Xiaorong; Kong, Lingying; Yang, Li

2015-08-01

This study aimed to explore the effects of recombinant human erythropoietin (rhEPO) on the growth of human breast cancer MDA-MB-231 cells in nude mice, and investigate its functions in regulating tumor growth, angiogenesis and apoptosis. A tumor-bearing nude mice model was established by subcutaneous injection of human breast cancer MDA-MB-231 cells. Two weeks later, the mice were randomly divided into four groups (n=6 for each group): negative control group, rhEPO group, EPO antibody group and EPO+EPO antibody group. Drugs were administered to the corresponding mice once every 3 days for five times. The size and weight of tumors were measured after the mice were sacrificed by cervical dislocation. The expression levels of EPO/EPOR, TNF-α, IL-10, and Bcl-2 in the tumor tissues were determined using RT-PCR and Western blot. The microvessel density (MVD) and expression of VEGF in the tumors were detected using immunohistochemistry. TUNEL assay was used to determine apoptosis in tumors. Results show that rhEPO significantly promoted the growth of MDA-MB-231 cells in nude mice (P<0.05). Compared with the negative control group, the expression levels of EPO, EPOR, TNF-α, IL-10, and VEGF, as well as the MVD values, were significantly elevated in the rhEPO group. However, the apoptotic index was significantly reduced (P<0.05). The ability of rhEPO to promote tumor growth may be associated with its functions in promoting microvessel formation and inhibiting tumor cell apoptosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Impact of blood hypercoagulability on in vitro fertilization outcomes: a prospective longitudinal observational study.

PubMed

Gerotziafas, Grigoris T; Van Dreden, Patrick; Mathieu d'Argent, Emmanuelle; Lefkou, Eleftheria; Grusse, Matthieu; Comtet, Marjorie; Sangare, Rabiatou; Ketatni, Hela; Larsen, Annette K; Elalamy, Ismail

2017-01-01

Blood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome. Thirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included. In the IVF-group, blood was collected at baseline, 5-8 days after administration of gonadotropin-releasing hormone agonist (GnRH), before and two weeks after administration of human follicular stimulating hormone (FSH). Pregnancy was monitored by measurement of β HCG performed 15 days after embryo transfer. Thrombin generation (TG), minimal tissue factor-triggered whole blood thromboelastometry (ROTEM®), procoagulant phospholipid clotting time (Procoag-PPL®), thrombomodulin (TMa), tissue factor activity (TFa), factor VIII (FVIII), factor von Willebrand (FvW), D-Dimers and fibrinogen were assessed at each time point. Positive IVF occurred in 15 women (40%). At baseline, the IVF-group showed significantly increased TG, TFa and TMa and significantly shorter Procoag-PPL versus the control group. After initiation of hormone treatment TG was significantly higher in the IVF-positive as compared to the IVF-negative group. At all studied points, the Procoag-PPL was significantly shorter and the levels of TFa were significantly higher in the IVF-negative group compared to the IVF-positive one. The D-Dimers were higher in the IVF negative as compared to IVF positive group. Multivariate analysis retained the Procoag-PPL and TG as predictors for the IVF outcome. Diagnosis of women with hypercoagulability and their stratification to risk of IVF failure using a model based on the Procoag-PPL and TG is a feasible strategy for the optimization of IVF efficiency that needs to be validated in prospective trials.

Comparison of a Novel Oxysterol Molecule and rhBMP2 Fusion Rates in a Rabbit Posterolateral Lumbar Spine Model

PubMed Central

Scott, Trevor P.; Phan, Kevin H.; Tian, Haijun; Suzuki, Akinobu; Montgomery, Scott R.; Johnson, Jared S.; Atti, Elisa; Tetratis, Sotirios; Pereira, Renata C.; Wang, Jeffrey C.; Daubs, Michael D.; Stappenbeck, Frank; Parhami, Farhad

2015-01-01

Background Context The non-union rate following lumbar spinal fusion is as high as 25%. Bone morphogenetic protein-2 (rhBMP2) has been used as a biological adjunct to promote bony fusion. However, recently there have been concerns about BMP2. Oxysterol 133 (Oxy133) has been shown to promote excellent fusion rates in rodent lumbar spine models and offers a potential alternative to rhBMP2. Purpose The purpose of this study was to compare the fusion rate of rhBMP2 and Oxy133 in a randomized controlled trial using a posterolateral lumbar rabbit spinal fusion model. Study Design This was a randomized control animal study. Methods Twenty-four male adult white New Zealand rabbits (3–3.5kg) underwent bilateral posterolateral lumbar spinal fusion at L4–L5. Rabbits were divided into 4 groups: control (A), 30 µg rhBMP2 (B), 20 mg Oxy133 (C), and 60 mg Oxy133 (D). At 4 weeks, fusion was evaluated by fluoroscopy, and at 8 weeks the rabbits were sacrificed and fusion was evaluated radiographically, by manual palpation, and with microCT. Dr. Parhami is a founder and Dr. Stappenbeck is the Director of Chemistry at MAX BioPharma, which has licensed the rights to Oxy133 from UCLA, both have financial interests in the technology presented here. UCLA holds equity in MAX BioPharma. All other authors have no conflicts of interest. Studies reported here were supported in part by the NIH/NIAMS grant RO1AR059794 and in part by MAX BioPharma that purchased the rabbits and provided Oxy133. Results Fusion rates by radiographic analysis at 8 weeks were: group A 40.0%, group B 91.7%, group C 91.7%, and group D 100%. Evaluation of fusion masses by manual palpation of excised spines after sacrifice showed the following fusion rates: group A 0%, group B 83.3%, group C 83.3%, and group D 90%. MicroCT scanning confirmed these findings. Conclusions These findings in a rabbit model demonstrate that both 20 mg dose and 60 mg dose Oxy133 promote fusion that is equivalent to fusion induced by 30 µg rhBMP2 and significantly greater than the control group. The present findings confirm that Oxy133 is a promising candidate for therapeutic development as an alternative to rhBMP2 to promote spinal fusion. PMID:25450659

rhBMP-2 (ACS and CRM formulations) overcomes pseudarthrosis in a New Zealand white rabbit posterolateral fusion model.

PubMed

Lawrence, James P; Waked, Walid; Gillon, Thomas J; White, Andrew P; Spock, Christopher R; Biswas, Debdut; Rosenberger, Patricia; Troiano, Nancy; Albert, Todd J; Grauer, Jonathan N

2007-05-15

The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.

The effects of GnRH analogue (buserelin) or hCG (Chorulon) on Day 12 of pregnancy on ovarian function, plasma hormone concentrations, conceptus growth and placentation in ewes and ewe lambs.

PubMed

Khan, T H; Beck, N F G; Khalid, M

2007-12-01

The objectives of this study were to determine the effect of GnRH analogue (buserelin) or human chorionic gonadotrophin (hCG, Chorulon) treatment on Day 12 of pregnancy on ovarian function, plasma hormone concentrations, conceptus growth and placentation in ewes and ewe lambs. After oestrus synchronization with progestagen sponges and eCG, all the animals were mated with fertile rams. Both ewes and ewe lambs (20 per treatment group) were given either normal saline or 4 microg GnRH or 200 IU hCG on Day 12 post-mating. Pre- and post-treatment plasma hormone concentrations were determined in seven pregnant animals per treatment group in samples collected 1h before and 0, 2, 4, 6, 8, 24, 48 and 72 h after treatment. Overall mean progesterone concentrations were higher (P<0.001) in ewes as compared with ewe lambs in saline-treated controls. GnRH or hCG treatment increased (P<0.001) mean plasma progesterone concentrations in both age groups, however, post-treatment concentrations were significantly (P<0.05) higher in ewes than in ewe lambs. Oestradiol concentrations were similar in the two control groups. In ewes, but not in ewe lambs, both GnRH and hCG treatments significantly (P<0.05) increased the mean oestradiol concentrations above pre-treatment levels. Moreover, post-treatment oestradiol concentrations in GnRH- and hCG-treated animals were significantly (P<0.05) higher than those in the saline-treated controls. LH release in response to GnRH treatment was greater (P<0.05) in ewes than in ewe lambs, whereas FSH release in ewes was less (P<0.05) than that of ewe lambs. The effects of GnRH or hCG on conceptus growth and placentation was determined at slaughter on Day 25. In ewes, GnRH treatment increased (P<0.05) luteal weight, amniotic sac width and length, and crown-rump length compared with controls, but had no effect on these parameters in ewe lambs. In ewes, hCG treatment also enhanced (P<0.05) luteal weight, amniotic sac width and length, crown-rump length, embryo weight and number of placentomes as compared with controls. In ewe lambs, there was no difference (P<0.05) between hCG and control groups in luteal weight, embryo weight and amniotic sac width but crown-rump length, amniotic sac length and the number of placentomes forming the placenta were greater (P<0.05). In conclusion, GnRH or hCG treatment on Day 12 of pregnancy can increase ovarian function, conceptus growth and placental attachment in ewes. However, these treatments were less effective in ewe lambs.

HLA A/B recombination in a white woman with the S-s-phenotype of the MNS system.

PubMed

Salaru, N N

1995-01-01

In cases of disputed parentage, the possibility of simultaneous occurrence of rare events in the population must be considered. PURPOSE--To report a case in which HLA-A/B recombination and homozygosity of a silent allele, typical of Negroes, in an individual apparently without this miscegenation were coexistent. METHODS--Alleged father, mother and dizygotic twin children were racially classified according to their apparent somatic characters. Blood group genetic markers of ABO, Rh, MNS, Kell, Duffy, HLA-A, -B systems were phenotyped; mother's HLA genotyping was performed by her parents test. RESULTS--The phenotype of the White mother, in the MNS system, was M+; N-; S-; s-. Alleged father and both twins were phenotipically compatible. The assumed maternity relating to both children was possible if mother presented an HLA-A/B recombination. CONCLUSION--In miscegenated populations, the breakup between ethnical appearance and blood group markers is foreseeable. Allele/haplotypic frequencies of these populations should be estimated. Casuistically, the association of events with low frequency in the population can be the cause of apparent exclusions of parentage.

Rare problems with RhD immunoglobulin for postnatal prophylaxis after large fetomaternal haemorrhage

PubMed Central

Kidson-Gerber, Giselle

2015-01-01

We report a case of unusually large fetomaternal haemorrhage in a RhD- patient; of symptomatic non-sustained haemolysis of fetal red cells in the maternal circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a failure to prevent RhD alloimmunisation. The haemolytic reaction is not previously reported in this patient group and we suggest would be limited to patients where the number of fetal red cells in the circulation is high. We advocate caution in treatment and spaced dosing of RhD immunoglobulin where the required dose is high, and refer readers to the WinRhoSDF™ RhD immunoglobulin product information for their updated dosing recommendations. There is a need for better understanding of pathophysiology and RhD immunoglobulin effects, to further reduce alloimmunisation rates, and we support the reporting of prophylaxis failures to haemovigilance programmes as is in place in the United Kingdom. PMID:27512480

Synthesis, crystal structure and electronic structure of the binary phase Rh2Cd5

NASA Astrophysics Data System (ADS)

Koley, Biplab; Chatterjee, S.; Jana, Partha P.

2017-02-01

A new phase in the Rh-Cd binary system - Rh2Cd5 has been identified and characterized by single crystal X-ray diffraction and Energy dispersive X-ray analysis. The stoichiometric compound Rh2Cd5 crystallizes with a unit cell containing 14 atoms, in the orthorhombic space group Pbam (55). The crystal structure of Rh2Cd5 can be described as a defect form of the In3Pd5 structure with ordered vacancies, formed of two 2D atomic layers with the stacking sequence: ABAB. The A type layers consist of (3.6.3.6)-Kagomé nets of Cd atoms while the B type layers consist of (35) (37)- nets of both Cd and Rh atoms. The stability of this line phase is investigated by first principle electronic structure calculations on the model of ordered Rh2Cd5.

Sex differences in the pharmacokinetics of recombinant human granulocyte colony-stimulating factor in the rat.

PubMed

Tanaka, H; Kaneko, T

1991-01-01

The pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) were studied in male and female rats. The serum concentration of rhG-CSF after iv and sc administration to male and female Sprague-Dawley rats at a dose of 5 and 100 micrograms/kg was investigated by a sandwich enzyme-linked immunosorbent assay. After iv administration, AUC and half-lives of rhG-CSF in female rats were smaller than those for male rats. The volume of distribution of rhG-CSF in female rats was not significantly different from that in male rats. After sc administration, AUC, mean residence time, and half-lives of elimination phase in female rats were smaller than those for male rats. The in vitro biological activities of rhG-CSF were investigated using [3H]thymidine uptake assay in cultures of bone marrow cells obtained from male and female rat femur. Female rat bone marrow cells showed a similar dose-response profile to rhG-CSF to that of male rat bone marrow cells. The effect of rhG-CSF administration in rats was a specific activity on the neutrophil lineage with an increase of neutrophils in peripheral blood. The in vivo effects of rhG-CSF after iv and sc administration to male and female rats at 5 and 100 micrograms/kg doses were determined. After 100 micrograms/kg administration, the neutrophil count in female rats was similar to that in male rats in the early period; however, the neutrophil count in female rats was lower than that in male rats 24 hr after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

LH response to GnRH blood test

MedlinePlus

... to tell the difference between primary and secondary hypogonadism . Hypogonadism is a condition in which the sex glands ... are the ovaries. Depending on the type of hypogonadism: Primary hypogonadism starts in the testicle or ovary ...

Recombinant human SDF-1α administration accelerates aneurysm neck reendothelialization in rabbit saccular aneurysm after flow diverter treatment.

PubMed

Li, Zifu; Zhao, Rui; Fang, Xinggen; Huang, Qinghai; Liu, Jianmin

2017-03-01

Reendothelialization in the aneurysm neck is pivotal to vascular repair for intracranial aneurysm after flow diverter (FD) implantation. Recombinant human stromal cell-derived factor 1α (rhSDF-1α) is a vital chemoattractant to stem cells and potentially facilitates reendothelialization. Here, we sought to investigate the therapeutic effects of intravenous administration of rhSDF-1α and uncover its potential mechanism for promoting aneurysm neck reendothelialization. Recombinant pET32a-186 plasmid was transformed into Escherichia coli to produce the rhSDF-1α protein with biological activity. FD was implanted into the elastase-induced saccular aneurysm in New Zealand white rabbits. rhSDF-1α (50 μg/kg/day) was intravenously administrated for consecutive 7 days after FD implantation. After these procedures, aneurysms were harvested after 2 or 4 weeks. Scanning electron microscopy was used to measure the neointima thickness and count the endothelial-like cells at aneurysm neck. Four weeks later, the mRNA levels of endothelial markers in the neointima at aneurysm neck were examined. Migration assay showed that rhSDF-1α could induce migration of endothelial progenitor cells in a dose-dependent manner. Two weeks after stent implantation, follow-up angiography showed partial aneurysm occlusion in one of each group and total aneurysm occlusion in 17 saccular aneurysm rabbits (9 of the rhSDF-1α group and 8 of the control group). No significant change of neointima thickness at aneurysm neck was observed. Intriguingly, more endothelial-like cells were observed at aneurysm neck in the rhSDF-1α group at 2 weeks (55 vs 13 cells per high-power field) and 4 weeks (104 vs 60 cells per high-power field). The mRNA levels of Tie-2, VE-cadherin, KDR and E-selectin were significantly enhanced compared with those of the control group. These results showed that intravenous administration of rhSDF-1α can accelerate reendothelialization in the aneurysm neck after FD implantation. Our study reveals an important role of rhSDF-1α in inducing aneurysm occlusion and suggests that it achieves its function through modulating the reendothelialization. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.