Evaluation of the repair of diaphyseal fracture of femoral bone using bone marrow mesenchymal stem cells in nicotine-bearing rat.

OBJECTIVE: Following bone fractures during accidents, some patients suffer from poor repair of bone fractures and subsequent aesthetic and psychological problems. One of the treatments is based on transplantation of stem cells (seeded on scaffolds) to the lesion site. Bone marrow stromal cells (BMSCs) are multivalent stem cells which are able to reproduce and differentiate into osteogenic cells. The objective of this study was to evaluate the treatment of bone fractures by means of transplantation of the latter cells in rats. METHODS: In this study, the therapeutic effect of mesenchymal stem cells from bone marrow adipocytes was evaluated in bone fractures. BMSCs were isolated from rat femur. Two sources of differentiated and non-differentiated osteocyte cells were provided and mixed with collagen in order to be transferred to animals divided in three main groups of model: nicotine, non-nicotine and control groups. After four weeks, the repair of the fracture that had been inflicted by a 2­mm drill into the diaphyseal region of the femoral bone was investigated by radiographic tests and histopathologic staining. RESULTS: The radiographic results as well as those of histopathologic staining showed that osteogenesis was more intensive in the non-nicotine group than in the nicotine group with differentiated and non-differentiated osteocyte cells. CONCLUSION: The transplantation of differentiated BMSCs to a bone lesion affected the repair of bone fractures while the nicotine agent played an important role in delaying the bone regeneration (Tab. 1, Fig. 8, Ref. 31).

Stable and sustained release liposomal formulations of celecoxib: In vitro and in vivo anti-tumor evaluation.

Celecoxib (CLX) is a selective COX-2 inhibitor with anticancer potential in a COX-2 dependent and independent manner. CLX's low water solubility has a dose limiting effect on its utilization in cancer treatment. Here, we developed liposomal drug delivery systems to allow a systemic administration and increase tumor accumulation of CLX based on the enhanced permeability and retention (EPR) mechanism. Nine liposomal formulations has been prepared with different phospholipid compositions; among them three sets of liposomal formulations were selected based on characterization and stability for further studies. Anti-tumor effects of CLX-entrapped liposomal formulations were tested in vitro by cytotoxicity test and in vivo in BALB/c mice bearing C26 colon carcinoma. Biodistribution of liposomal-CLX has been studied by radiolabeling of CLX with I125.The selected formulations had average size of about 100 nm, a narrow monomodal distribution with storage stability of at least one year at 4 °C. The HSPC/DSPG/cholesterol/DSPE-PEG2000/CLX (65/10/10/5/10 M ratio) liposomal formulation had slowest release profile and greatest antitumor effects in vivo. This liposomal I125CLX formulation had a three times more accumulation in tumor site in comparison to the free I125CLX. Liposomal CLX may serve as a safe, slow release and effective anti-tumor agent and merits further investigation.

Longitudinal sequential biventricular assessment in adults with transposition of the great arteries and relationship with adverse outcomes.

BACKGROUND: In a cohort of congenitally corrected transposition of the great arteries (cc-TGA) and transposition of the great arteries after atrial switch procedure (d-TGA) the study objectives were: 1) to assess the change of quantitative systemic right ventricle (sRV) parameters over time and; 2) to examine the relationship of quantitative sRV parameters with adverse clinical outcomes. METHODS AND RESULTS: Single-center cohort study that included 49 (39%) cc-TGA and 76 (61%) d-TGA patients >18years who had at least one MUGA sRV assessment, 18/39 had more than one respectively. The primary clinical endpoint was all-cause mortality, heart transplantation and/or heart failure hospitalization. At a median clinical follow-up of 7years following the first MUGA, the primary endpoint occurred more often in cc-TGA versus d-TGA patients (18 (36.7%) vs. 9 (11.8%), p=0.03). Median time between the MUGA assessments was 5.8 (cc-TGA) and 4.9years (d-TGA). At last MUGA follow-up: 6 (33%) cc-TGA/14 (36%) d-TGA patients showed a significant decline in sRVEF (>5%); 6 (33%) cc-TGA/17 (44%) d-TGA patients had a significant increase in sRVEDVi; and 7 (39%) cc-TGA/19 (49%) PA-TGA patients had a significant increase in sRVESVi. Baseline sRV parameters were not associated with the primary end point or sRV changes over time. CONCLUSIONS: An important proportion of both patient cohorts demonstrated a significant change in sRV parameters over time and these are likely related to multiple factors that vary between individuals given population heterogeneity. The TGA patients have distinct clinical trajectories with increased adverse heart failure outcomes in the cc-TGA population and sRV parameters were not related to adverse heart failure events in either group.

Correlation of Gankyrin oncoprotein overexpression with histopathological grade in prostate cancer.

Prostate cancer is the second most commonly diagnosed cancer among men worldwide. Identifying new prognostic and predictive biomarkers will help stratification of prostate cancer patients for a better treatment. Gankyrin is a novel oncoprotein which regulates cell cycle and protein degradation. Gankyrin overexpression correlated with the malignant phenotypes and promotes the tumorigenicity and metastasis in many cancers. However, there are not any reports on the role of Gankyrin in prostate cancer. Therefore, this study was designed to investigate the expression of Gankyrin in prostate cancer and analyze its correlation with some clinicopathological characteristics. We characterized the expression of gankyrin in fifty five prostate cancer specimens and twenty non-cancerous tissues by immunohistochemical staining and the results were correlated with clinical characteristics and pathological parameters.Results showed that Gankyrin was expressed in 41 of 55 (74%) prostate cancer patients and its expression was significantly higher than corresponding adjacent normal tissues (p<0.001). Gankyrin overexpression was significantly correlated with histopathological tumor grade, Gleason score and tumor differentiation (P=0.002). These findings showed that Gankyrin is mainly overexpressed in high grade prostate tumors so it may have a significant role in prostate cancer progress and it May serve as a useful biomarker for the identification of aggressive prostate cancers.

Subclinical hypothyroidism and diabetic nephropathy in Iranian patients with type 2 diabetes.

PURPOSE: Association of subclinical hypothyroidism with type 2 diabetes and its complications has been previously documented. These reports were, however, inconclusive and mainly gathered from Chinese and East Asian populations. In this study, we aimed to determine the prevalence of subclinical hypothyroidism and its relationship with diabetic nephropathy in Iranian individuals with type 2 diabetes, drawn from a white Middle Eastern population with an increasing prevalence of diabetes. METHODS: In this cross-sectional study, 255 Iranian participants with type 2 diabetes and without history of thyroid disorders were included. Patients with TSH > 4.2 mIU/L and normal T4 were classified as having subclinical hypothyroidism. Diabetic nephropathy was diagnosed based on abnormal 24-h urinary albumin or protein measurements (24-h urinary albumin ≥30 mg/day or 24-h urinary protein ≥150 mg/day). Multivariate logistic regression was employed to obtain the OR for the relationship between subclinical hypothyroidism and diabetic nephropathy. RESULTS: We found that subclinical hypothyroidism and diabetic nephropathy were as prevalent as 18.1 and 41.2 %, respectively, among the participants. We also found that subclinical hypothyroidism was independently associated with higher rates of diabetic nephropathy, after multivariable adjustment (OR [95 % CI] 3.23 [1.42-7.37], p = 0.005). CONCLUSIONS: We found that the prevalence of subclinical hypothyroidism in Iranian diabetic population was among the highest rates reported to date. Our data supported the independent association of subclinical hypothyroidism with diabetic nephropathy, calling for further investigations to evaluate their longitudinal associations.

An inexpensive and rapid method for extracting papilionoid genomic DNA from herbarium specimens.

Three DNA extraction protocols were compared for their ability to yield DNA from the leaves of herbarium specimens of nine species from nine genera of the Papilionoideae. We tested two protocols that use classic procedures for lysis and purification with cetyl trimethylammonium bromide (CTAB); a third protocol used a Nucleospin Plant kit. DNA obtained from all three procedures was quantified and tested by PCR. Test results indicated the superiority of one of the CTAB protocols. We made some modifications, developing a protocol that produced high-quality DNA from all nine species. The modification involved the use of a lower EDTA concentration (20 mM instead of 50 mM) and a higher beta-mercaptoethanol concentration (1% instead of 0.4%) in the extraction buffer. The modified protocol avoids the necessity for a second DNA precipitation step. This new CTAB protocol includes the use of 1.4 M NaCl, 20 mM EDTA and 1% beta-mercaptoethanol in the extraction; DNA precipitation time is reduced. A reduction in contaminating metabolites (such as PCR inhibitors) in the sample mixtures and lower costs for reagents are characteristics of this modified protocol; the cost of analysis per sample was lowered, compared to previous options. The quality of DNA was suitable for PCR amplification. This is a practical alternative to more difficult, time-consuming and expensive protocols.

A model describing Debaryomyces hansenii growth and substrate consumption during a smear soft cheese deacidification and ripening.

A mechanistic model for Debaryomyces hansenii growth and substrate consumption, lactose conversion into lactate by lactic acid bacteria, as well as lactose and lactate transfer from the core toward the rind was established. The model described the first step (14 d) of the ripening of a smear soft cheese and included the effects of temperature and relative humidity of the ripening chamber on the kinetic parameters. Experimental data were collected from experiments carried out in an aseptic pilot scale ripening chamber under 9 different combinations of temperature (8, 12, and 16 degrees C) and relative humidity (85, 93, and 99%) according to a complete experimental design. The model considered the cheese as a system with 2 compartments (rind and core) and included 5 state evolution equations and 16 parameters. The model succeeded in predicting D. hansenii growth and lactose and lactate concentrations during the first step of ripening (curd deacidification) in core and rind. The nonlinear data-fitting method allowed the determination of tight confidence intervals for the model parameters. The residual standard error (RSE) between model predictions and experimental data was close to the experimental standard deviation between repeated experiments.

Prophylaxie de l'endocardite infectieuse en chirurgie dentaire

Chez les sujets porteurs de cardiopathies; une antibioprophylaxie bien adaptee et appliquee lors des situations ou gestes invasifs dentaires devrait diminuer le taux des greffes osleriennes qui sont grevees d'une morbi- mortalite importante. La sphere bucco-dentaire reste le site le plus pourvoyeur de bacteriemies. La prescription de l'antibioprophylaxie depend de la cardiopathie sous-jacente et du type de geste bucco-dentaire a realiser. Son efficacite a ete clairement prouvee par de nombreux auteurs qui ont demontre une reduction extremement variable mais significative du risque d'endocardite infectieuse. Le succes de cette prevention est etroitement lie a la diffusion et a l'application des recommandations sur l'antibioprophylaxie et a une meilleure collaboration Medecins- Chirurgiens dentistes

Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders.

A prospective study was undertaken in 87 healthy pregnant women with thyroid antibodies and normal thyroid function at initial presentation [asymptomatic autoimmune thyroid disorders (AITD)]. The aims of the study were to assess whether women with AITD constitute a group at risk of developing subclinical hypothyroidism during pregnancy, and whether a mild thyroid function impairment may be associated with obstetrical repercussions. The women investigated were selected among a cohort of 1660 consecutive pregnancies on the basis of 1) no previous history of thyroid disease, 2) euthyroidism at initial presentation, and 3) positive thyroglobulin antibodies and/or thyroid peroxidase antibodies (TPO-Ab). Women with AITD had a basal TSH value significantly higher, albeit still normal, in the first trimester (1.6 vs. 0.9 mU/L; P < 0.001) than that in women with healthy pregnancies used as controls. Despite a 60% average reduction in TPO-Ab titers during gestation, serum TSH remained higher in women with AITD than in controls throughout gestation: at delivery, 40% of the cases had serum TSH levels above 3 mU/L, and 16% had serum TSH levels above 4 mU/L. A TRH test carried out in the days after parturition showed an exaggerated response in 50% of the cases. Furthermore, free T4 concentrations were in the range of hypothyroid values in 42% of the women. Obstetrical repercussions were observed, namely increased rates of spontaneous miscarriage and premature deliveries. In conclusion, women with asymptomatic AITD who are euthyroid in early pregnancy carry a significant risk of developing hypothyroidism progressively during gestation, despite a marked reduction in antibody titers. Hypothyroidism results from the reduced ability of the gland to adjust to the changes in thyroidal economy associated with pregnancy. At the individual level, progression to subclinical hypothyroidism was broadly predictable on the basis of serum TSH levels and TPO-Ab titers in the first trimester. Hence, these parameters provide useful markers to identify women who carry a higher risk, allowing for a close monitoring of thyroid function during pregnancy and the administration of L-T4 in specific cases. Taken together with the known incidences of postpartum thyroiditis and hypothyroidism in women with AITD, the present observations in our opinion justify systematic screening of thyroid autoimmunity during pregnancy.

Inflammatory symptoms in breast cancer. Correlations with growth rate, clinicopathologic variables, and evolution.

Based on two pretreatment evaluations, doubling time (DT) was calculated in 75 cases of invasive breast cancer (BC). The cases studied were more or less equally distributed between three DT groups: fast-growing tumors (DT less than 90 days), intermediate cases (DT between 90 and 180 days), and slow-growing tumors (DT greater than 180 days. A correlation was found to exist between DT and patient age and, to an even greater extent, between DT and pathologic prognostic indicators such as histologic grading and nuclear grade. Inflammatory symptoms were not associated with DT, but were closely related to the size of the tumor and regional lymph node involvement. The date of detection of distant metastases depended heavily on the DT of the BC:BC with shorter DT = earlier metastatic spread. The presence of inflammatory signs was also decisive: within each DT category, inflammatory BC metastases were both more frequent and precocious.

Right ventricular--saphenous vein graft fistula. Unusual complication of aorta-coronary bypass grafting.

A fistula between the right ventricle and a saphenous vein graft aneurysm developed 10 years following aorta-coronary bypass. Surgical repair was attempted, but the autopsy finding of a large myocardial infarction raised the possibility of a "coronary steal" phenomenon.

Massive arterial air embolism due to rupture of pulsatile assist device: successful treatment in the hyperbaric chamber.

We present the case of a patient who had rupture of a pulsatile assist device (PAD) accompanied by massive air embolism, and the treatment that brought it to a successful outcome. After rupture of the skin of the PAD balloon, a massive amount of air was injected into the ascending aorta. The patient was placed in Trendelenburg position and cooled in deep hypothermia with cardiopulmonary bypass. He was given 1 gm of methylprednisolone intravenously, and the aortic valve replacement and double vein bypass graft were performed. After completion of the operation, the patient was partially rewarmed to 30 degrees C central temperature and transported by ambulance to a hyperbaric chamber where he was compressed to 6 atmospheres absolute 9 hours after the accident with clinical signs of severe brain dysfunction. The patient recovered completely and was discharged from the hospital on the tenth postoperative day.

Androgen receptor in human skin cytosol.

Human skin, an accessible tissue, is an androgen target organ. We have measured the androgen-binding capacity of human skin cytosol using either 5 alpha[3H]dihydrotestosterone ([3H]DHT) or [3H]methyltrienolone ([3H]R-1881) as ligand. Samples were incubated for 20 h at 0 C, and dextran-coated charcoal was used to separate bound from free steroids. The androgen receptor has a high affinity for both ligands (0.23 +/- 0.04 nM for [3H]DHT; 0.32 +/- 0.16 nM for [3H]R-1881). Testosterone, cyproterone acetate, and, to a lesser extent, estradiol also bind this protein. Progesterone displaces R-1881 from its binding sites, whereas its 5 alpha-reduced metabolite somewhat inhibits DHT binding. The highest binding capacity is measured in cytosol of skin from external genitalia (129.14 +/- 58.0 fmol/g skin; n = 34); it is lower in pubic skin (21.8 +/- 13 fmol/g skin; n = 6). There is no variation as a function of age or sex in genital skin; the higher concentrations observed in the cytosol of pubic skin of women compared to that of men are probably related to lower levels of endogenous steroids. Whereas most patients with the complete form of the testicular feminization syndrome do not have detectable concentrations of androgen receptor, one patient with apparent complete clinical androgen insensitivity had a normal androgen-binding capacity. The parity of values in genital skin from men and women, the absence of variation with age, and the presence of a cytosolic androgen receptor in some androgen-insensitive patients suggest that the androgen receptor in human skin cytosol is not regulated by androgens.

Cost containment via expense rationalization in open-heart surgery.

Hospital costs and the fees of the surgeon, assistant, anesthesiologist, and cardiologist were reviewed in a community hospital doing 425 cardiac operations in the year 1977. Each item of the bill was analyzed and discussed with each department of the hospital. Changes made in the routine saved approximately $1000 per patient--16% for patients having mitral valves replacement (MVR), 15% for those having aortic valve replacement (AVR), 21% for those having saphenous vein bypass grafts (SVBG), and 23% for pediatric cases. The areas most likely to yield economic reductions without alteration of the quality of care are operating room, patient room, respiratory therapy, and pharmacy. Making the nurses, scrub technicians, surgical assistants, residents, and staff surgeons aware of the cost of each item and periodically discussing the alternatives could yield surprisingly large savings.

Aneurysm of saphenous vein bypass graft to coronary artery.

A few cases of aneurysmal dilatation of autogenous vein grafts to peripheral arteries have been reported. However, to our knowledge, no case of this complication in coronary artery vein bypass grafts have been found. We are presenting a case of a vein graft aneurysm which appeared 6 months postoperatively. The patient had had an aortic valve replacement and a vein bypass graft to the right coronary artery.