The effects of N-acetylcysteine on cisplatin induced cardiotoxicity.

OBJECTIVES: Recent studies reported that oxidative stress is an important mechanism that contributes to cisplatin induced cardiotoxicity. In the present study, the effects of N-acetylcysteine (NAC), which is an antioxidant, on cisplatin induced cardiotoxicity were investigated in a rat model. METHODS: Thirty two rats were separated into 4 equal groups: Control, NAC-250, CP (cisplatin), CP+NAC. Rats in the experimental groups were treated with a single dose of cisplatin intraperitoneally (ip) (10 mg/kg) and NAC (ip, 250 mg/kg) for 3 consecutive days. At the end of the experiment, cardiotoxicity was determined from plasma CK-MB, LDH, cTnI and cardiac myosin light chain-1 (CMLC-1) levels. In the tissue samples, total oxidant capacity (TOC), total antioxidant capacity (TAC), lipid hydroperoxide (ROOH) and thiol levels were measured. The hearts were also analyzed histopathologically. RESULTS: It was determined that cisplatin increased the tissue TOC, ROOH levels and decreased TAC and thiol levels. NAC administration after cisplatin treatment was observed to have ameliorated histological and functional changes in heart. CONCLUSIONS: In conclusion, the results of this experimental study suggested that oxidative stress had a serious effect on cisplatin cardiotoxicity, and NAC could be used as a therapeutic agent in addition to standard cisplatin treatment protocols (Tab. 3, Fig. 1, Ref. 35).

Peri-operative delineation of non-melanoma skin cancer margins in vivo with handheld reflectance confocal microscopy and video-mosaicking.

BACKGROUND: The surgical removal of non-melanoma skin cancers (NMSCs) is guided by the pathologic examination of margins. However, the preparation of histopathology is time consuming, labour-intensive and requires separate laboratory infrastructure. Furthermore, when histopathology indicates positive margins, patients must return for re-excisions. Reflectance confocal microscopy (RCM) with a new video-mosaicking approach can noninvasively delineate margins directly on patients and potentially guide surgery in real-time, augmenting the traditional approaches of histopathology. OBJECTIVE: To assess a new peri-operative RCM video-mosaicking approach for comprehensive delineation of NMSC margins on patients in vivo. METHODS: Thirty-five patients undergoing Mohs micrographic surgery (MMS) in the Mohs surgery unit at Memorial Sloan Kettering Cancer Center, New York, NY were included in the study. RCM imaging was performed before and after the first staged excision by acquiring videos along the surgical margins (epidermal, peripheral and deep dermal) of each wound, which were subsequently processed into video-mosaics. Two RCM evaluators read and assessed video-mosaics, and subsequently compared to the corresponding Mohs frozen histopathology. RESULTS: Reflectance confocal microscopy videos and video-mosaics displayed acceptable imaging quality (resolution and contrast), pre-operatively in 32/35 (91%) NMSC lesions and intra-operatively in 29/35 lesions (83%). Pre-operative delineation of margins correlated with the histopathology in 32/35 (91%) lesions. Intra-operative delineation correlated in 10/14 (71%) lesions for the presence of residual tumour and in 18/21 (86%) lesions for absence. Sensitivity/specificity were 71%/86% and 86%/81% for two RCM video-mosaic evaluators, and overall agreement was 80% and 83% with histopathology, with moderate inter-evaluator agreement (k = 0.59, P ≤ 0.0002). CONCLUSIONS: Peri-operative RCM video-mosaicking of NMSC margins directly on patients may potentially guide surgery in real-time, serve as an adjunct to histopathology, reduce time spent in clinic and reduce the need for re-excisions. Further testing in larger studies is needed.

Thyroid Hormone Withdrawal Further Exacerbates Oxidative Stress in Patients with Thyroid Carcinoma.

PURPOSE: Hypothyroidism has profound effects on multiple organs and systems including cellular oxidative damage. Thus, we aimed to investigate the effects of acute hypothyroidism on oxidative stress in patients with differentiated thyroid carcinoma (DTC). PATIENTS: 33 patients with DTC were involved in the study. 23 healthy subjects matched for age and body mass index (BMI) served as control group. Fasting blood sample was obtained for the determination of blood chemistry, lipids, myeloperoxidase (MPO) activity, total lipid hydroperoxide (LHP), pyrrolized protein, protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP) and thiol levels before and after thyroid hormone withdrawal (THW) in patients with DTC. RESULTS: MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels were significantly higher, but thiol levels were significantly lower in patients with DTC while on L-thyroxine treatment than those of healthy subjects. At acute hypothyroid status after THW, MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels further increased, thiol levels further decreased in patients with DTC as compared to healthy subjects and to their on L-thyroxine treatment period. CONCLUSIONS: This study showed an increased oxidative stress in patients with DTC which is further exacerbated with acute hypothyroidism upon THW. This situation may have treatment implications such as antioxidant therapy, at least during THW.

Demographical, laboratory and associated findings in patients with perniosis.

BACKGROUND: Perniosis is a cold-induced inflammatory disorder of the acral areas. The objective of this study was to investigate the demographic characteristics, associated factors, clinical and laboratory findings in patients with perniosis and to compare those findings between patients who had recurrent and acute disease. METHODS: Thirty-four patients with perniosis were investigated retrospectively for age, gender, occupation, smoking and diet histories, associated diseases, family history of perniosis, precipitating factors, the month of onset and the duration of perniosis, the distribution of the lesions and the results of laboratory investigations. RESULTS: Fifteen patients were male and 19 were female. The ages of the patients ranged from 15 to 57 years. Thirteen patients were working as sales people, which was the most common occupation. Sixteen patients were smokers. While 25 of the patients had encountered perniosis for the first time, in 9 of the patients, there were recurrent lesions. Diseases other than perniosis were recorded in 6 of the patients. The laboratory tests revealed mild leukopenia in 2, antinuclear antibody (ANA) positivity in 3, mild rise in albumin level in serum protein electrophoresis in 1 patient. ANA positivity was significantly higher in patients with recurrent disease. CONCLUSION: Perniosis was more common in women and below 40 years. We found no significant laboratory findings except ANA positivity in patients with recurrent perniosis.

The major complications of transpedicular vertebroplasty.

OBJECT: Vertebroplasty is a well-known technique used to treat pain associated with vertebral compression fractures. Despite a success rate of up to 90% in different series, the procedure is often associated with major complications such as cord and root compression, epidural and subdural hematomas (SDHs), and pulmonary emboli, as well as other minor complications. In this study, the authors discuss the major complications of transpedicular vertebroplasty and their clinical implications during the postoperative course. METHODS: Vertebroplasty was performed in 12 vertebrae of 7 patients. Five patients had osteoporotic compression fractures, 1 had tumoral compression fractures, and 1 had a traumatic fracture. Two patients had foraminal leakage, 1 had epidural leakage, 1 had subdural cement leakage, 2 had a spinal SDH, and the last had a split fracture after the procedure. RESULTS: Three patients had paraparesis (2 had SDHs and 1 had epidural cement leakage), 3 had root symptoms, and 1 had lower back pain. Two of the 3 patients with paraparesis recovered after evacuation of the SDH and subdural cement; however, 1 patient with paraparesis did not recover after epidural cement leakage, despite cement evacuation. Two patients with foraminal leakage and 1 with subdural cement leakage had root symptoms and recovered after evacuation and conservative treatment. The patient with the split fracture had no neurological symptoms and recovered with conservative treatment. CONCLUSIONS: Transpedicular vertebroplasty may have major complications, such as a spinal SDH and/or cement leakage into the epidural and subdural spaces, even when performed by experienced spinal surgeons. Early diagnosis with CT and intervention may prevent worsening of these complications.

The European Organization for Research and Treatment of Cancer core quality of life questionnaire (QLQ-C30 version 3.0 Turkish) in cancer patients receiving palliative radiotherapy.

The aim of this study was to evaluate the efficacy of palliative radiotherapy in patients with advanced cancer in terms of improvement in the quality of life [quality of life questionnaire (QLQ)], and to assess the correlation between the Eastern Cooperative Oncology Group (ECOG) performance status and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (Turkish version 3.0). A total of 88 patients with advanced malignant disease treated with palliative radiotherapy were included in the study. All patients completed the EORTC QLQ-C30 questionnaire before and after treatment, and the patient performance status during the pre-treatment and post-treatment phase (ECOG 2) was correlated to the EORTC QLQ C-30 with subscales. Most patients (87.5%) had metastatic disease, and the remaining (12.5%) had locally advanced disease. Comparing the patients in terms of performance status, those with a better performance status (

Nuclear and mitochondrial DNA microsatellite instability in gastrointestinal stromal tumors.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Nuclear (nMSI) and mitochondrial microsatellite instability (mtMSI) play important roles in tumorigenesis in various organs. The aim of this study was to evaluate the role of nMSI and mtMSI in GISTs. METHODS: Samples from 74 mesenchymal tumors were collected. nMSI and mtMSI were examined by microsatellite assay at BAT26 and D310 mononucleotide repeats in mtDNA, respectively. We compared nMSI, mtMSI and clinicopathologic features, including patient age and sex, tumor location, tumor size, presence of tumor ulceration and presence of distant metastasis, for 51 GISTs for which these data were available. RESULTS: nMSI and mtMSI were detected in 3 (5%) and 10 (16%) of the 62 GISTs, respectively. There was no significant relationship between nMSI, mtMSI and clinicopathologic features. CONCLUSION: These results suggest that mtMSI may play a role, but that nMSI may play little role in the development of GISTs.

The diagnostic value of on-site cytopathological evaluation and cell block preparation in fine-needle aspiration cytology of liver masses.

OBJECTIVE: The aims of this study were to evaluate the typing accuracy of conventional smear (CS), cell block (CB) preparations and combined use of both procedures (CS + CB) for the diagnosis of hepatic malignancies and to determine whether immediate on-site cytopathological evaluation improves the diagnostic yield of liver fine-needle aspiration cytology (FNAC). METHODS: Ultrasound-guided FNABs were performed on 323 consecutive cases with liver masses between December 2002 and December 2004. Histologically and/or clinically correlated 167 cases were included in the study. Preliminary FNAB results, results of CS, CB, and combined use of CS and CB were compared regarding diagnostic sensitivity, specificity, and accuracy for the diagnosis of malignancy. Subtyping accuracies of different methods were also compared. RESULTS: The sensitivity of on-site cytopathological examination and CS were both 92.8%. The sensitivity of CS + CB was slightly better than that of CB (93.5% versus 84.8%). Specificity of all procedures was achieved 100%. Diagnostic accuracy of on-site cytopathological evaluation, CS, CB, and CS + CB were 93.9%, 93.9%, 87.2%, and 94.5%, respectively. A specific subtype diagnosis of malignant tumours could be rendered accurately on the basis of preliminary diagnosis in 71%, CS in 75.4%, CB in 78.3% and combined approach in 92% of cases. In terms of typing accuracy, 87.5% of HCCs, 93.2% of adenocarcinomas, 92.3% of neuroendocrine carcinomas, 100% of lymphomas and 100% of other malignant tumours were correctly subclassified in the final cytopathological diagnosis. The agreement between preliminary diagnosis and final cytopathological diagnosis was 77.2%. CONCLUSION: With use of on-site cytopathological evaluation and combined use of CS and CB, the diagnostic accuracy of liver tumours approaches 100% and also significantly improve diagnostic and subtyping accuracy of liver malignancies.

Expression of growth factors in the gingival crevice fluid of patients with phenytoin-induced gingival enlargement.

The mechanism underlying phenytoin (PHT)-induced gingival enlargement (GE) is not yet known. The aim of the present study was to investigate transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) profiles in the gingival crevice fluid (GCF) of patients with PHT-induced GE and to compare the results with healthy controls. Five PHT-treated patients and five healthy subjects with normal periodontal tissue were included in this study. GCF samples were collected from (i) enlarged gingival sites in patients receiving PHT (GE+); (ii) non-enlarged gingival sites in the same patients (GE-); (iii) normal gingival sites of healthy subjects (control). The levels of TGF-beta1, PDGF-BB and bFGF in the GCF samples were analysed by ELISA. The results showed that the total amounts of TGF-beta1 and PDGF-BB in the GE+ group were higher than in the GE- group and significantly higher than in the control group (P < 0.05). However, no significant differences were found between the groups when the concentrations of these growth factors were compared. bFGF levels were not compared as this growth factor could be detected in only 33, 41 and 44% of the GE+, GE- and control GCF samples, respectively. These results show that TGF-beta1 and PDGF-BB are readily detectable in GCF obtained from enlarged and non-enlarged sites of PHT recipients and suggest that since the amounts were markedly higher at the GE+ than the GE- sites, the systemic administration of PHT has a pronounced localised effect on the levels of these growth factors. Moreover, our findings provide evidence that both TGF-beta1 and PDGF-BB are closely associated with the clinical manifestation of PHT-induced GE.

[Early functional results of arthroscopic surgery for ankle lesions]. / Ayak bilegi lezyonlarinda artroskopik cerrahinin erken dönem fonksiyonel sonuçlari.

OBJECTIVES: We evaluated early functional results of arthroscopic surgery in the treatment of ankle pathologies. METHODS: A total of 32 patients (17 males, 15 females; mean age 35 years; range 17 to 54 years) underwent arthroscopic surgery for ankle lesions, which included osteochondritis dissecans (n=21), synovitis (n=6), impingement syndrome (n=4), and synovial chondromatosis. Arthroscopic surgery was performed in the left ankle in 15 patients, and in the right ankle in 17 patients. Osteochondral lesions were assessed by the Berndt-Harty, arthroscopic views by the Ferkel-Cheng classification systems. Preoperative and postoperative functional evaluations were made using the Freiburg ankle scoring system. The mean follow-up was 42 months (range 11 to 84 months). RESULTS: There was no improvement in Freiburg scores within nine weeks in patients with osteochondritis dissecans, whose preoperative mean score was 66. However, at the end of 3.5 months, the Freiburg scores manifested a marked increase to a mean of 88. Functional scores increased from 72 to 90, and from 80 to 95 in patients with synovitis and impingement syndrome, respectively, at the end of nine weeks. The patient with synovial chondromatosis became symptom-free after two months. Complications included breakage of a drill in one patient and development of reflex sympathetic dystrophy in another. CONCLUSION: Arthroscopic surgery for ankle lesions decreases surgical morbidity and promotes functional improvement, especially in patients with osteochondritis dissecans, synovitis, and impingement syndrome.

Increased insulin-like growth factor-I levels in women with polycystic ovary syndrome, and beneficial effects of metformin therapy.

We aimed to investigate whether metformin would reverse the endocrinopathy of polycystic ovary syndrome (PCOS), allowing resumption of cyclic ovulation and regular menses, and whether metformin causes any change in the serum concentration of insulin-like growth factor-I (IGF-I) in patients with PCOS. Fifty-eight women with PCOS participated in the study and received metformin at a dose of 850 mg three times a day (total 2550 mg) for 16 weeks. Serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol, free testosterone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, fasting insulin, IGF-I, sex hormone binding globulin and insulin-like growth factor binding protein-1 (IGFBP-1) were evaluated before and after metformin treatment. Patients were divided into two groups as responders and non-responders according to the achievement of regular menstrual periods. The mean IGF-I levels decreased significantly on metformin therapy. After 16 weeks of metformin treatment, 55.17% of PCOS patients achieved regular menses. Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders. In conclusion, we observed that elevated IGF-I levels may have a crucial role in many consequences of PCOS in addition to hyperinsulinemia. By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses. Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.

Effect of propylthiouracil on adenosine deaminase activity and thyroid function in patients with psoriasis.

BACKGROUND: T-cell activation has been implicated in the pathogenesis of psoriasis; adenosine deaminase (ADA) activity has been considered as a marker of T-cell activation. The antithyroid drug propylthiouracil (PTU) has recently been shown to have beneficial effects on psoriatic lesions, probably by acting on the immune system. OBJECTIVES: To investigate whether ADA activity may be related to psoriasis and whether oral PTU affects ADA activity and gives clinical improvement in psoriatic patients. METHODS: ADA activities were measured in plasma, erythrocyte and tissue samples of patients with psoriasis before and after 2 months of treatment with either PTU 100 mg three times daily or PTU plus thyroxine 25 microg once daily (to prevent possible hypothyroidism, which may be induced by PTU) as well as in healthy controls. The severity of the disease was evaluated before and after treatment according to Psoriasis Area and Severity Index (PASI) scores. Routine analyses and thyroid function tests were also carried out during the study. RESULTS: All patients showed significant clinical improvement in their lesions and decreased PASI scores after the treatments. Elevated baseline ADA activities in skin and plasma were found to be lower, and decreased baseline erythrocyte ADA was higher, after the treatments in all patients, and they were not different from control values. Although thyroid function tests were not affected by the treatments, serum thyroid-stimulating hormone levels were found to be higher after the treatments, and there was a larger increase in patients treated with PTU alone. However, none of the patients had clinical hypothyroidism or cytopenia. CONCLUSIONS: ADA activity may be clinically useful for indicating T-cell activation in psoriasis. Because of its antiproliferative and immunomodulatory effects, antioxidant potential and low toxicity, PTU may be an effective agent in the treatment of psoriasis.

The evaluation of lipid peroxidation and adenosine deaminase activity in patients with Behçet's disease.

OBJECTIVE: Despite unknown etiology, immunologic alterations and neutrophil hyperfunctions may be involved in the etiopathogenesis of Behçet's Disease (BD). The purpose of the study was to investigate whether adenosine deaminase (ADA) activity, accepted as a nonspecific marker of T lymphocyte activation, may have a potential role in BD, and also may be related to the production of reactive oxygen species (ROS) by neutrophils. DESIGN AND METHODS: ADA activities and malondialdehyde (MDA; endproduct of lipid peroxidation induced by ROS) levels in both plasma and erythrocytes were spectrophotometrically measured in 25 patients with BD and also in 25 healthy controls. RESULTS: ADA activity was found to be higher in plasma, but lower in erythrocytes; plasma and erythrocyte MDA levels were higher in BD patients than those of controls. In addition, plasma ADA activity was positively related to MDA levels in both plasma (p < 0.05) and erythrocytes (p < 0.01). There was also positive correlation between MDA levels (p < 0.05), but negative correlations between ADA activities (p < 0.01) and also between ADA and MDA values in erythrocytes (p < 0.01) of BD patients. CONCLUSION: These findings may provide some evidence for a potential role of T lymphocyte activation in BD as reflected by increased plasma ADA activity, and for the presence of possible interrelationship between activated T cells and neutrophil hyperfunctions, such as ROS generation, as reflected by increased MDA levels.

Circulating IL-2, IL-10 and TNF-alpha in chronic hepatitis B: their relations to HBeAg status and the activity of liver disease.

BACKGROUND/AIMS: Preferential production of immunoregulatory cytokines may play an important role in the pathogenesis of chronic hepatitis B. We aimed to determine the serum levels of IL-2, IL-10 and TNF-alpha in patients with chronic hepatitis B and to correlate these findings with the activity of liver disease, HBeAg/anti-HBe status and replication level of the virus. METHODOLOGY: Seventy-two chronic hepatitis B patients were categorized into 4 groups according to activity of liver disease and HBeAg status. Group 1 (n = 13): HBeAg and HBV DNA-positive with persistently normal ALT. Group 2 (n = 20): HBeAg and HBV DNA-positive patients with persistently elevated ALT. Group 3 (n = 19): HBeAg and HBV DNA-negative patients with persistently normal ALT. Group 4 (n = 20): HBeAg-negative patients with persistently elevated ALT and variable serum HBV DNA. IL-2, IL-10 and TNFa levels were determined in stored patient sera. RESULTS: Apart from group 1 patients, all patients groups had higher IL-2 levels compared to controls suggesting that IL-2 production is increased when liver disease becomes active in HBeAg-positive phase of HBV infection. Only group 2 patients had elevated IL-10 levels compared to controls. None of the HBeAg-negative patients had detectable TNF-alpha levels while 64% HBeAg-positive patients had elevated levels of TNF-alpha irrespective of the activity of liver disease. Except TNF-alpha, no association was found between HBV DNA status and the presence or absence of detectable cytokines in circulation. CONCLUSIONS: Our results suggest that circulating cytokine profile in chronic hepatitis B is related with the HBeAg status, replication level of the virus and the activity of liver disease.

Myocardial hemodynamic and metabolic changes during abdominal insufflation with carbon dioxide.

It is a well-known fact that laparoscopic procedures performed with carbon dioxide insufflation impair myocardial function. In this study, we aimed to determine the safety limitations of various intra-abdominal pressure values during abdominal insufflation with carbon dioxide. Of the 24 mongrel dogs, 6 were assigned to one of four different pressure groups (10, 15, 20 and 30 mm Hg), respectively. Cardiac output, right/left heart pressures, and the first derivative of ventricular pressure were monitored. Myocardial oxygen consumption, myocardial lactate/oxygen extraction, tissue lactate and adenosine triphosphate levels were determined. Measurements were performed initially as a control, at 15-min intervals during 1 h of insufflation and 1 h after desufflation. At 10 mm Hg carbon dioxide pressure, hemodynamic and metabolic parameters were not significantly different. Cardiac output decreased significantly in the 20 and 30 mm Hg groups (p < 0.05: 10, 15 vs. 20, 30 mm Hg). Although cardiac output did not change at 15 mm Hg, the dp/dt value was significantly reduced. Cardiac output at the 60th min was 1,960+/-75 ml/min in the 10 mm Hg group, 1,885+/-40 ml/min in the 15 mm Hg group, 1,770+/-45 ml/min in the 20 mm Hg group and 1,695+/-40 ml/min in the 30 mm Hg group. Myocardial oxygen consumption was reduced at 15, 20 and 30 mm Hg (p < 0.05: 10 vs. 15, 20 and 30 mm Hg). In the myocardial tissue, ATP decreased from 19+/-2 to 12+/-1.2 micromol/g at 15 mm Hg, from 19+/-1.9 to 9.4+/-1.3 micromol/g at 20 mm Hg and from 18+/-3.2 to 8.2+/-1.9 micromol/g at 30 mm Hg. Changes in hemodynamic and metabolic parameters of the heart are reversible and may not lead to any significant impairments in patients having normal cardiopulmonary function, but pose a risk in patients with respiratory disease and limited myocardial reserve.

Simplified retroperfusion system preserves the myocardial function during acute coronary artery occlusion.

It is known that coronary venous retroperfusion restores the blood flow to the ischemic myocardium, resulting in reduction of infarct size and improvement in left-ventricular pump function. In this study, we used an animal model to investigate the effects of a simplified coronary venous retroperfusion system on myocardial hemodynamics. Twenty dogs were entered in this study. All dogs underwent fifteen minutes occlusion of the left anterior descending artery. For the rest of the experiment the dogs were randomized into two groups: the control group (n = 10) underwent a further 2 hours left anterior descending artery occlusion, then clamps were released and the animals were observed for 6 hours. In the retroperfusion group (n = 10) a simple aortocoronary sinus connection was made and retrograde perfusion achieved with an outflow of 43 +/- 6 ml/min. Retrograde coronary sinus perfusion was maintained for three hours and then the dogs were observed for six hours. Tissue adenosine triphosphate levels were 6 +/- 3 mumol/g in the control group and 12 +/- 2 mumol/g in the retroperfusion group (p < 0.05) 6 hours after reperfusion. Creatine phosphokinase levels were 99 +/- 11 IU/L in the control group and 42 +/- 8 IU/L in the retroperfusion group 6 hours after reperfusion (p < 0.05). Cardiac index was 63 +/- 4 ml/kg/min in the control group and 79 +/- 2 ml/kg/min in the retroperfusion group 6 hours after retroperfusion (p < 0.05). Left-ventricular stroke-work index at a pulmonary capillary artery wedge pressure of 20 mmHg was 0.54 +/- 0.06 g.m/kg in the retroperfusion group and 0.29 +/- 0.03 g.m/kg in the control group 6 hours after reperfusion (p < 0.05). It is concluded that myocardial hemodynamic and biochemical function can be preserved by simplified coronary sinus retroperfusion.

Pro-inflammatory cytokines downregulate platelet derived growth factor-alpha receptor gene expression in human osteoblastic cells.

Platelet derived growth factor (PDGF) is thought to play a significant role in bone repair and regeneration. We previously demonstrated that PDGF-AA binding can be modulated by interleukin-1 (IL-1). We now report that TNF-alpha significantly reduces PDGF-AA binding by decreasing the number of PDGF-alpha receptor subunits on the surface of normal human osteoblastic cells. This inhibition is likely due to a decrease in synthesis of PDGF-alpha receptors since TNF-alpha causes a relatively rapid decrease in PDGF-alpha receptor mRNA levels as determined by Northern blot analysis. The physiologic importance of this inhibition is demonstrated by a TNF-alpha induced decrease in PDGF-AA stimulated tyrosine kinase activity. When saturating concentrations of TNF-alpha were used, the addition of IL-1 further inhibited PDGF-AA binding and further decreased surface expression of PDGF-alpha receptors. In contrast, other mediators such as IL-6, PTH, 1,25(OH)2 vit D3, hydrocortisone, PGE2, bFGF, and IGF-1 had no effect. These results suggest that binding to the PDGF-alpha receptor is decreased by the strong pro-inflammatory cytokines such as IL-1 beta and TNF-alpha rather than as a general response to mediators important in bone resorption or bone formation. TNF-alpha and IL-1 are often co-expressed during destructive inflammatory processes. Thus, TNF-alpha and IL-1 may work in concert to limit the response of osteoblastic cells to PDGF-AA during periods of osseous inflammation.

Hypoxia-induced necrotizing enterocolitis in the immature rat: the role of lipid peroxidation and management by vitamin E.

The authors developed an experimental model of necrotizing enterocolitis (NEC) by hypoxia-reoxygenation, and determined the content of malondialdehyde levels as an index of lipid peroxidation, related with a free-radical reaction in the gastrointestinal tract of newborn rats. They also investigated the role of vitamin E, an antioxidant, in this free-radical injury. The study was performed on 1-day-old rats. The 30 rat pups were divided into three groups. Hypoxia was induced by placing the pups in a 100% carbon dioxide chamber for 5 minutes. The pups were reoxygenated with 100% oxygen for 5 minutes. Group 1 (n = 10) was subjected to hypoxia-reoxygenation and killed 3 days after hypoxia. Group 2 (n = 10) was subjected to hypoxia-reoxygenation and treated with vitamin E (30 IU/kg/d intraperitoneally) for the next 3 days, and killed. Group 3 (n = 10) rats served as controls. The histopathology of the intestinal lesions in group 1 animals was characteristic of ischemic injury and ranged from superficial epithelial damage with villous shortening to transmural necrosis. In the vitamin E-treated animals these lesions were milder. The malondialdehyde levels of group 1 were significantly higher than those of the other two groups (P < .001). This study shows that oxidant-mediated lipid peroxidation injury plays a central role in mediating hypoxia-induced intestinal necrosis and suggests that vitamin E may play a therapeutic role in NEC.