Biomedical subjects

T Pehlivan

Publications and source records attributed to T Pehlivan.

12 recordsLinked to original sources

PubMed2004

Proliferation of ovarian theca-interstitial cells is modulated by antioxidants and oxidative stress.

BACKGROUND: Maintenance of ovarian homeostasis requires precise regulation of proliferation of thecal- interstitial (T-I) cells. Recent evidence indicates that oxidative stress and antioxidants modulate proliferation of various tissues under both physiological and pathological conditions. This study evaluated the effects of oxidative stress and antioxidants on T-I proliferation. METHODS: Rat T-I cells were cultured in serum-free medium and proliferation was assessed by determination of DNA synthesis using the thymidine incorporation assay, by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and by direct counting of steroidogenically active cells and steroidogenically inactive cells. RESULTS: Antioxidants and reactive oxygen scavengers induced a dose-dependent decrease of T-I proliferation. Vitamin E succinate was inhibitory at 10-100 micro mol/l, ebselen was inhibitory at 0.3-30 micro mol/l, and superoxide dismutase was inhibitory at 300-1000 IU/ml. In contrast, oxidative stress resulted in a biphasic effect. Modest oxidative stress induced by 1 mmol/l hypoxanthine and xanthine oxidase (3-30 micro U/ml) stimulated proliferation of T-I cells, while greater oxidative stress induced by xanthine oxidase (1 mU/ml) profoundly inhibited proliferation. Direct cell counting demonstrated comparable effects on steroidogenically active and inactive cells. CONCLUSIONS: Reactive oxygen species may play a role in the regulation of growth of ovarian mesenchyme. Under pathological conditions, such as those encountered in polycystic ovary syndrome, excessive oxidative stress and depletion of antioxidants may contribute to ovarian mesenchymal hyperplasia.

Animals↗

PubMed2003

Impact of preimplantation genetic diagnosis on IVF outcome in implantation failure patients.

Implantation failure (IF) is defined as three or more failed IVF attempts, and preimplantation genetic diagnosis (PGD) is being used in these patients to improve IVF outcome. PGD was performed in 49 implantation failure patients with a mean number of 4.2 +/- 1.6 previous IVF failures, and in nine fertile controls. Fluorescence in-situ hybridization (FISH) on blastomeres from biopsied day 3 embryos was performed for chromosomes 13, 16, 18, 21, 22, X and Y. There was a significantly higher rate of chromosomal abnormalities (67.4%) compared with controls (36.3%). In 57 cycles, a pregnancy rate of 34.0% and an implantation rate of 19.8% was observed in implantation failure patients compared with controls (33.3 and 24.1% respectively), with all the pregnancies in the implantation failure group coming from the transfer of at least one chromosomally normal blastocyst on day 5. It is concluded that in IVF patients, use of PGD along with blastocyst transfer improves IVF outcome.

Adult↗

PubMed2003

Chromosomal abnormalities and embryo development in recurrent miscarriage couples.

BACKGROUND: Chromosomal abnormalities are an important cause of spontaneous abortion and recurrent miscarriage (RM). Therefore, we have analysed the incidence of chromosomal abnormalities and embryo development in patients with RM. METHODS: Preimplantation genetic diagnosis (PGD) was performed on 71 couples with RM and 28 couples undergoing PGD for sex-linked diseases (control group). Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by fluorescence in-situ hybridization. RESULTS: The implantation rate in RM patients was 28% and three patients (13%) miscarried. The percentage of abnormal embryos was significantly increased (P < 0.0001) in RM patients compared with controls (70.7 versus 45.1%). All of the embryos were abnormal in 19 cycles (22.1%) and repeated PGD cycles yielded similar rates of chromosomal abnormalities in 14 couples. Anomalies for chromosomes 16 and 22 were significantly higher (P < 0.01) in RM cases. In the RM population, euploid embryos reached the blastocyst stage more frequently than abnormal embryos (61.7 versus 24.9%; P < 0.0001). CONCLUSIONS: RM is associated with a higher incidence of chromosomally abnormal embryos, of which some are able to develop to the blastocyst stage. IVF plus PGD is an important step in the management of these couples, but the technique has to move towards a full chromosome analysis.

Abortion, Habitual↗

PubMed2001

Measles seroprevalence in Izmir with special emphasis on measles vaccination policy for Turkey.

BACKGROUND: Measles outbreaks seem to occur every 2- to 3-year intervals in Turkey. However, sero-epidemiological studies are limited. Knowing the prevalence of measles susceptibility as measured either by serologic markers of immunity or surveys of vaccination coverage is an important tool to assess the risk for measles outbreaks. METHODS: In order to determine the seroprevalence of measles antibodies among a 1 to 29-year-old population in Izmir (Turkey) and to develop the best vaccination policy for measles, a total of 600 people aged from 1 to 29 were selected for the study with cluster sampling. The information on sociodemographic characteristics, vaccination status and measles history was gathered for each participant. Measles-specific IgG antibodies were screened qualitatively by using microenzyme immune assay for 595 subjects. RESULTS: Of the 595 participants screened for the measles antibodies, 56 (9.4%) were seronegative. The proportion of the susceptible individuals in the age groups of 1-4, 5-9, 10-14, 15-19 and 20-29 was 20.0, 10.4, 6.0, 10.3 and 3.0%, respectively. The logistic regression analysis showed that none of the independent characteristics (sex, socioeconomic status, past measles history, vaccination status) with the exception of age group, was significantly associated with measles seronegativity. CONCLUSION: The optimal measles vaccination policy for Turkey may be to increase vaccination coverage above 90%, to conduct a catch-up campaign covering persons aged 1-19, regardless of previous vaccination status. Another factor to consider is to adopt a routine two-dose vaccination, giving the first dose at 12-15 months of age and the second dose at school entry.

Adolescent↗

PubMed2001

Activin stimulates proliferation of rat ovarian thecal-interstitial cells.

There is growing evidence that the function of ovarian theca-interstitial (T-I) cells may be modulated by paracrine actions of activin, inhibin, and follistatin. Furthermore, either dysregulation, dysfunction, or both, of these peptides may play a role in conditions associated with T-I hyperplasia, such as polycystic ovary syndrome (PCOS) and hyperthecosis. This study was designed to evaluate the role of activin, inhibin, and follistatin in the modulation of T-I cell proliferation. Interaction of these peptides with insulin-like growth factor-I (IGF-I), a known stimulator of T-I cell proliferation, was also assessed. Purified rat T-I cells were cultured for 48 h in chemically defined media and with or without activin (3-30 ng/ml), inhibin (3-30 ng/ml), follistatin (100 ng/ml), and/or IGF-I (10 nM). T-I cell proliferation was assessed using radiolabeled thymidine incorporation assay. Activin alone stimulated proliferation of T-I cells in a dose-dependent fashion (by up to 320% above control; P < 0.001), whereas inhibin alone or follistatin alone had no significant effect. Inhibin had also no effect on activin-induced proliferation. Follistatin significantly reduced the stimulatory effects of activin and decreased proliferation by up to 46% (P < 0.01) below the level attained in the presence of activin alone. IGF-I (10 nM), at a dose producing a near-maximal effect, increased proliferation by 175% above control (P < 0.001); insulin (10 nM) increased proliferation by 52% above control (P < 0.03). A combination of IGF-I (10 nM) and activin (30 ng/ml) resulted in a 1090% increase of proliferation above control (P < 0.001); this stimulatory effect was significantly greater than that achieved in the presence of either activin alone or IGF-I alone (P < 0.001). Similarly, a combination of insulin (10 nM) and activin (30 ng/ml) increased proliferation by 506% above control levels. Flow cytometry evaluation revealed that activin increased the proportion of actively dividing cells (in S or G2/M phase of the cell cycle) by 42% (P < 0.02), whereas IGF-I had no effect on the proportion of actively dividing cells. The present findings indicate that an activin-follistatin system may be involved in the regulation of the size of ovarian thecal-stromal compartment. In view of the synergy between activin and IGF-I, and the difference in the effects on the cell cycle distribution, stimulation of T-I proliferation by these agents is likely to be mediated via separate transduction pathways. Excess activin or insufficient follistatin may contribute to T-I hyperplasia.

Activins↗

PubMed2001

Effects of transforming growth factors-alpha and -beta on proliferation and apoptosis of rat theca-interstitial cells.

Ovarian development, follicular growth and atresia require mechanisms regulating proliferation and death of ovarian cells including theca-interstitial (T-I) cells. Transforming growth factors-alpha and -beta (TGF-alpha and TGF-beta) are well recognized local modulators of T-I function. This study was performed to evaluate the effects of TGF-alpha and TGF-beta on ovarian T-I cell proliferation, differentiation and apoptosis. T-I cells from immature Sprague-Dawley rats were purified and incubated in chemically defined media. Proliferation was assessed by [3H]thymidine incorporation assay and by cell counting. Steroidogenically active cells were identified histochemically by detection of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity. DNA was extracted and apoptosis was identified by detection of internucleosomal DNA cleavage producing the characteristic 'ladder pattern' of low-molecular weight (LMW) DNA following agarose gel electrophoresis. Quantification of apoptosis was carried out with the aid of 3'-end labeling of DNA fragments with [32P]-dideoxy-ATP. TGF-alpha and TGF-beta stimulated [3H]thymidine incorporation by 2.2- to 3.1-fold and 1.7- to 3.4-fold respectively (P<0.005). A combination of TGF-alpha and TGF-beta produced a synergistic increase in DNA synthesis by 6.7-fold (at 1 ng/ml of each TGF-alpha and TGF-beta; P<0.001) and tenfold (at 10 ng/ml of each TGF-alpha and TGF-beta; P<0.001). Cell counting revealed that TGF-alpha increased the total number of cells 2.8-fold and TGF-beta 2.8-fold. The combination of TGF-alpha and TGF-beta increased the total cell count 3.2-fold, compared with control (P<0.05). The percentage of the steroidogenically active cells was 37+/-9% (mean+/-s.e.m. ) in the control cultures, 50+/-5% in the presence of TGF-alpha, 42+/-8% in the presence of TGF-beta, and 47+/-13% in the presence of both TGF-alpha and TGF-beta. TGF-alpha decreased apoptosis by 63+/-14% (P=0.02) while TGF-beta had no statistically significant effect. TGF-alpha in combination with TGF-beta produced the greatest inhibition of apoptosis by 73+/-8% (P=0.01). These findings demonstrate that TGF-alpha and -beta stimulate proliferation of both steroidogenically active and inactive T-I cells. Furthermore, TGF-alpha alone and in combination with TGF-beta protects T-I cells from apoptotic death. These effects of TGFs may be important in physiologic maintenance of ovarian mesenchymal growth and homeostasis as well as in pathophysiologic conditions associated with excessive growth of the T-I compartment, such as polycystic ovary syndrome.

3-Hydroxysteroid Dehydrogenases↗

PubMed1999

Immunogenicity study of a combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis vaccine used to reconstitute a freeze-dried Haemophilus influenzae type b vaccine (DTaP-IPV//PRP-T) administered simultaneously with a hepatitis B vaccine at two, three and four months of life.

This study was designed to assess the immunogenicity of a vaccine combining diphtheria and tetanus toxoids, acellular pertussis vaccine, and inactivated poliovirus vaccine reconstituting Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (DTaP-IPV//PRP-T; Pasteur Mérieux Connaught, Lyon, France) administered simultaneously in association with hepatitis B vaccine (RECOMBIVAX (¿trade mark omitted¿) Merck, Sharp & Dohme, West Point, PA, USA) for the primary immunization of infants. The vaccines were administered at two, three and four months of age. One hundred and sixty-two healthy infants, aged 8-10 weeks, were enrolled in the study. Blood samples were taken before the first dose and 4 weeks after the third dose. The infants were observed for 15 minutes after vaccination for any immediate reaction. Adverse events requiring a medical consultation were recorded by the parents in a diary over the 7 days following vaccination. Four weeks after the third immunization, the percentages of infants fulfilling seroconversion criteria were 98.9% for pertussis toxin, 95.9% for filamentous haemagglutinin, 100.0% for tetanus, 100.0% for diphtheria, 99.3% for poliovirus type 1, 100.0% for both poliovirus types 2 and 3, 98.0% for Haemophilus influenzae type b, and 100% for hepatitis B surface antigen. No vaccine-related serious adverse event was reported. The simultaneous administration of DTaP-IPV//PRP-T and hepatitis B vaccines at two, three and four months of age yielded clinically satisfactory immune responses to all antigens compared with historical controls and gave a good safety profile.

Diphtheria-Tetanus-Pertussis Vaccine↗

PubMed1999

GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease.

Previous studies have shown that patients with deletion of distal human chromosome arm 8p may have congenital heart disease and other physical anomalies. The gene encoding GATA-4, a zinc finger transcription factor implicated in cardiac gene expression and development, localizes to chromosome region 8p23.1. To examine whether GATA-4 deficiency is present in patients with monosomy of 8p23.1 with congenital heart disease, we performed fluorescence in situ hybridization (FISH) with a GATA4 probe on cells from a series of patients with interstitial deletion of 8p23.1. Four individuals with del(8)(p23.1) and congenital heart disease were found to be haploinsufficient at the GATA4 locus by FISH. The GATA4 gene was not deleted in a fifth patient with del(8)(p23.1) who lacked cardiac anomalies. FISH analysis on cells from 48 individuals with congenital heart disease and normal karyotypes failed to detect any submicroscopic deletions at the GATA4 locus. We conclude that haploinsufficiency at the GATA4 locus is often seen in patients with del(8)(p23.1) and congenital heart disease. Based on these findings and recent studies showing that haploinsufficiency for other cardiac transcription factor genes (e.g., TBX5, NKX2-5) causes congenital heart disease, we postulate that GATA-4 deficiency may contribute to the phenotype of patients with monosomy of 8p23.1.

Adult↗

PubMed1999

Priming effect, immunogenicity and safety of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey.

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular (two component) pertussis (DTaP) combination vaccine, a randomized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule group (As-S). The third group (N = 137) also received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are referred to as the associated, long schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. The immune response to Hib capsular polysaccharide, however, was significantly lower after combined administration (Co-S group) than after associated (As-S group) administration (P < 0.0001), with a similar trend among both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02 microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population, possibly due to differences in reporting practice. Our results indicate (1) that the combination vaccine, DTaP//PRP-T, represents an important improvement over the existing uncombined vaccines; (2) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines; and (3) that it is feasible and valuable to co-randomize combination vaccine studies in sufficiently different geographical areas and child populations.

Belgium↗

PubMed1997

Immunogenicity and safety of Haemophilus influenzae type b capsular polysaccharide tetanus conjugate vaccine (PRP-T) presented in a dual-chamber syringe with DTP.

Separate injections of Haemophilus influenzae type b capsular polysaccharide-tetanus conjugate (PRP-T) vaccine and diphtheria-tetanus-pertussis (DTP) reconstitution of freeze-dried PRP-T vaccine with liquid DTP vaccine have been shown to be safe and immunogenic in infants. The present study was conducted to test the safety and immunogenicity of the liquid combination vaccine administered to young infants in the dual-chamber syringe. The study was a monocenter, open clinical trial of 3 month-old infants receiving PRP-T and DTP vaccines in the dual-chamber syringe reconstituted prior to injection. Healthy infants were immunized according to a 3, 4 and 5 months-of-age schedule. The vaccine was administered in a dual-chamber syringe, ready to use with two chambers. The proximal chamber contained freeze-dried PRP-T and the distal chamber contained liquid combination-vaccine DTP. The freeze-dried PRP-T vaccine was reconstituted with the liquid DTP vaccine in the same unidose dual-chamber syringe (0.5 mL) and was injected intramuscularly into the deltoid region. Blood sampling was performed prior to vaccination at 3 months of age and after the third vaccination at 6 months. The primary end-point was the serological response to PRP-T vaccine as expressed by the percentage of infants with an antibody titer greater than or equal to 1 microgram/mL. The reactogenicity was expressed as the percentage of reported local and systemic reactions. A total of 108 infants were included in the study and received the dual-chamber syringe vaccine. After the third injection, all the infants had a PRP antibody titer greater than or equal to 0.15 microgram/mL and 94.4% of infants had a PRP antibody titer greater than or equal to 1 microgram/mL; the pertussis agglutinin titers were over the threshold 40 and 80 in all infants and 98.1% were over the threshold 320. After the third injection, all the infants had diphtheria antibody titers greater than 0.1 IU/mL and 83.3% had titers greater than 1 IU/mL; all the infants had tetanus antibody titers greater than 0.1 IU/mL and 97.2% had results over 1 IU/mL. Thirty-seven infants (34.6%) had local reactions and 64.5% had systemic reactions. The dual-chamber syringe may reduce the cost of vaccine delivery, as well as the workload, and increase the vaccine acceptability and coverage rate of vaccines.

Antibodies, Viral↗

PubMedDate not supplied

Estradiol regulates monocyte chemotactic protein-1 in human coronary artery smooth muscle cells: a mechanism for its antiatherogenic effect.

OBJECTIVE: The protective effect of estrogen against early atherosclerosis in animal models is well documented, but the mechanisms responsible for this effect are not well understood. The earliest recognizable event in the pathogenesis of atherosclerosis is an increased recruitment of macrophages into the arterial subendothelium. Macrophages first play a protective role by removing low-density lipoproteins, but when the cholesterol is in excess, macrophages are converted into foam cells and form atheromas. Recent human and animal data indicate that the recruitment of macrophages to the arterial wall is mediated by monocyte chemotactic protein-1 (MCP-1). We hypothesized that one of the mechanisms of estrogen's protective effect against atherosclerosis may be the down-regulation of MCP-1 expression in the arterial wall. DESIGN: Human coronary artery smooth muscle cells were replicated to confluence in smooth muscle cell basal medium supplemented with growth factors and 5% fetal bovine serum. Before each experiment, cells were incubated for 24 h with phenol red-free medium containing 5% charcoal-stripped calf serum, and then they were treated with various concentrations of 17beta-estradiol as well as selective estrogen receptor (ER) modulators, raloxifene and tamoxifen. MCP-1 messenger ribonucleic acid (mRNA) levels were quantified by Northern blots. MCP-1 protein was quantified using an enzyme-linked immunosorbent assay. ER expression was evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: Human coronary artery smooth muscle cells expressed MCP-1 mRNA and produced MCP-1 protein. Estradiol induced up to 40% inhibition in mRNA expression at concentrations 10-9 M and higher. Raloxifene and tamoxifen also resulted in an inhibition, but the inhibition was less than when induced by estradiol. Estradiol also inhibited the MCP-1 protein production in a concentration-dependent manner (p < 0.05). Coronary smooth muscle cells expressed both ERalpha and ERbeta. CONCLUSION: Our findings suggest that one of the mechanisms by which estrogen prevents atherosclerosis is by down-regulating MCP-1 expression, thus decreasing macrophage recruitment to the arterial wall.

Animals↗

PubMedDate not supplied

Perioperative immunonutrition ameliorates the postoperative immune depression in patients with gastrointestinal system cancer (prospective clinical study in 42 patients).

Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.

Colorectal Neoplasms↗