Oxysterol species: reliable markers of oxidative stress in diabetes mellitus.

PURPOSE: To assess the plasma oxysterol species 7-ketocholesterol (7-Kchol) and cholestane-3ß,5α,6ß-triol (chol-triol) as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus (DM). METHODS: In total, 26 type 1 and 80 type 2 diabetes patients, along with 205 age- and gender-matched healthy controls, were included in this study. Oxysterols were quantified by liquid chromatography coupled with tandem mass spectrometry and N,N-dimethylglycine derivatization. Correlations between oxysterols and clinical/biochemical characteristics of the diabetes patients, and factors affecting 7-Kchol and chol-triol, were also determined. RESULTS: Plasma 7-Kchol and chol-triol levels were significantly higher in type 1 and type 2 diabetes patients compared to healthy controls (P < 0.001). Significant positive correlations were observed between oxysterol levels and levels of glycated hemoglobin (HbA1c), glucose, serum total cholesterol, low-density lipoprotein, very-low-density lipoprotein, and triglycerides, as well as the number of coronary risk factors. Statins, oral hypoglycemic agents, and antihypertensive agents reduced the levels of oxysterols in type 2 diabetes patients. Statin use, HbA1c levels, and the number of coronary risk factors accounted for 98.8% of the changes in 7-Kchol levels, and total cholesterol, smoking status, and the number of coronary risk factors accounted for 77.3% of the changes in chol-triol levels in type 2 diabetes patients. CONCLUSIONS: Plasma oxysterol levels in DM, and particularly type 2 DM, may yield complementary information regarding oxidative stress for the clinical follow-up of diabetes patients, especially those with coronary risk factors.

Data on dopant characteristics and band alignment of CdTe cells with and without a ZnO highly-resistive-transparent buffer layer.

Photovoltaic enhancement of cadmium telluride (CdTe) thin film solar cells using a 50 nm thick, atomic-layer-deposited zinc oxide (ZnO) buffer film was reported in "Enhancement of the photocurrent and efficiency of CdTe solar cells suppressing the front contact reflection using a highly-resistive ZnO buffer layer" (Kartopu et al., 2019) [1]. Data presented here are the dopant profiles of two solar cells prepared side-by-side, one with and one without the ZnO highly resistive transparent (HRT) buffer, which displayed an open-circuit potential (Voc) difference of 25 mV (in favor of the no-buffer device), as well as their simulated device data. The concentration of absorber dopant atoms (arsenic) was measured using the secondary ion mass spectroscopy (SIMS) method, while the density of active dopants was calculated from the capacitance-voltage (CV) measurements. The solar cell simulation data was obtained using the SCAPS software, a one-dimensional solar cell simulation programme. The presented data indicates a small loss (around 20 mV) of Voc for the HRT buffered cells.

Vitamin D replacement ameliorates serum lipoprotein functions, adipokine profile and subclinical atherosclerosis in pre-menopausal women.

BACKGROUND AND AIMS: Low vitamin D (vitD) has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation are not clarified. We evaluated the impact of vitD normalization on HDL cholesterol efflux capacity (CEC), which inversely correlates with CV risk, the proatherogenic serum cholesterol loading capacity (CLC), adipokine profile and subclinical atherosclerosis. METHODS AND RESULTS: Healthy premenopausal women with vitD deficiency (n = 31) underwent supplementation. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AIx), measured with standard techniques. HDL CEC and serum CLC were measured by a radioisotopic and fluorimetric assay, respectively. Malondialdehyde (MDA) in HDL was quantified by the TBARS assay. Pre-ß HDL was assessed by 2D-electrophoresis. Serum adipokines were measured by ELISA. VitD replacement restored normal levels of serum 25-hydroxyvitamin D (25OHD) and significantly improved FMD (+4%; p < 0.001), PWV (-4.1%: p < 0.001) and AIx (-16.1%; p < 0.001). Total CEC was significantly improved (+19.5%; p = 0.003), with a specific increase in the ABCA1-mediated CEC (+70.8%; p < 0.001). HDL-MDA slightly but significantly decreased (-9.6%; p = 0.027), while no difference was detected in pre-ß HDL. No change was observed in aqueous diffusion nor in the ABCG1-mediated CEC. Serum CLC was significantly reduced (-13.3%; p = 0.026). Levels of adiponectin were increased (+50.6%; p < 0.0001) and resistin levels were decreased (-24.3%; p < 0.0001). After vitD replacement, an inverse relationship was found linking the ABCA1-mediated CEC with pre-ß HDL (r2 = 0.346; p < 0.001) and resistin (r2 = 0.220; p = 0.009). CONCLUSION: Our data support vitD supplementation for CV risk prevention.

Nonsurgical cerebrospinal fluid rhinorrhea in invasive macroprolactinoma: incidence, radiological, and clinicopathological features.

CONTEXT: Macroprolactinomas (MPRLs) may result in nonsurgical (spontaneous or dopamine agonist induced) cerebrospinal fluid (CSF) rhinorrhea; however, the incidence of and mechanisms underlying this phenomenon are poorly understood. OBJECTIVE: The objective of the study was to determine the incidence of nonsurgical rhinorrhea and identify biochemical, radiological, and histopathological factors associated with leakage. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of MPRL patients (n = 114) was compared with patients with nonfunctioning pituitary adenoma (NFA) (n = 181) seen over a 19-yr period (1985-2004). MAIN OUTCOME MEASURES: Incidence of CSF rhinorrhea, factors predictive of leakage, and differential expression of candidate markers of invasiveness were measured. RESULTS: Nonsurgical CSF rhinorrhea occurred in 8.7% of MPRLs (10 of 114) [2.6% spontaneous (three of 114), 6.1% dopamine agonist induced (seven of 114)], whereas no NFAs developed nonsurgical rhinorrhea. There was a clear male preponderance in MPRLs with nonsurgical rhinorrhea (males to females, 9:1, P = 0.008). Dopamine agonist resistance was more frequent in MPRLs with rhinorrhea than with MPRLs without rhinorrhea [30% (n = 10) vs. 5% (n = 104) P = 0.003]. Baseline prolactin levels, rate of prolactin decline in response to dopamine agonists, and tumor volume at diagnosis did not predict CSF leakage. Candidate markers of invasiveness, specifically the protease-activated receptor 1 and e-cadherin expression scores and tumor macrophage density, were not significantly different between groups; MPRL+CSF rhinorrhea (n = 6), MPRL without CSF rhinorrhea (n = 9), and NFAs (n = 9). CONCLUSIONS: The incidence of nonsurgical CSF rhinorrhea in MPRL patients (8.7%) is higher than expected. Dopamine agonist resistance is more common in MPRLs with CSF rhinorrhea; however, whether this is a mechanistic relationship requires further study. Protease-activated receptor 1 expression, e-cadherin expression, and macrophage infiltration rates do not distinguish tumors with from those without CSF rhinorrhea.

Hyperprolactinemia of pregnancy is not associated with increased in vivo platelet activity and shortened in vitro bleeding times.

The aim of the study is to investigate whether platelet activity is increased by hyperprolactinemia during pregnancy as reflected by beta-thromboglobulin level. Forty-eight healthy, pregnant, and 30 healthy, non-pregnant women were investigated with respect to platelet count, collagen/ADP and collagen/epinephrine closure times, beta-thromboglobulin and prolactin levels. The comparison of the variables between the two groups was made by Mann-Whitney U test. The correlation analyses were performed by Spearman's rank correlation test. Our results revealed that platelet counts, collagen/ADP and collagen/epinephrine closure times and beta-thromboglobulin showed no statistically significant differences between pregnant and non-pregnant women. We found no significant correlation between prolactin and collagen/ADP closure time (r = 0.175), between prolactin and collagen/epinephrine closure time (r = -0.112) and between prolactin and beta-thromboglobulin (r = 0.220) in pregnant women. Our findings suggest that platelet activity is comparable during pregnant and non-pregnant states and there is no significant effect of prolactin on platelet function in vivo as reflected by beta-thromboglobulin level.

The continuing scourge of congenital syphilis in 21st century: a case report.

Although the rate of congenital syphilis is declining in developed countries, a significant increase has been observed in the underdeveloped countries. Unfortunately, little concern is raised about the increasing numbers of babies born with congenital syphilis. The procedure to prevent congenital syphilis through antenatal screening and treatment is well established. But implementation of effective programs has proved very difficult especially in resource--poor settings. Congenital syphilis, if not treated promptly and adequately, may result in significant physical and emotional squeal in children. A case of complicated late congenital syphilis is reported in order to emphasize that syphilis is still present nowadays, and re-emerging many countries even some of the industrialized ones. Most of the cases can not be prevented by routine antenatal screening. Thus it is essential to develop strategies to prevent sexually transmitted disease from being a hidden and neglected problem.

Resistance to thyroid hormone associated with autoimmune thyroid disease in a Turkish family.

The syndrome of resistance to thyroid hormone (RTH) is characterized by impaired tissue responses to thyroid hormone. Hashimoto's thyroiditis is the most common thyroid autoimmune disease. We present a Turkish family with both RTH and Hashimoto's thyroiditis. RTH was detected through the presence of point mutation in thyroid hormone receptor (TR), and Hashimoto's thyroiditis was diagnosed due to the presence of thyroid autoantibodies. The proposita, her affected mother as well as her unaffected sister have thyroid autoantibodies consistent with Hashimoto's thyroiditis, and a heterozygous point mutation in exon 10 encoding the ligand (3,3',5-L-T3)-binding domain of the TRbeta gene was detected in both the proposita and the mother. The mutation is a replacement of cytosine for guanine in codon 453 (CCT->GCT) producing a missense mutation substituting a normal proline with an alanine (P453A), which reduces the affinity for T3 to 17% of that of the normal TRbeta. Both also have modest elevation of serum TSH levels. In severe RTH, marked elevation of thyroid hormone concentrations in the absence of suppressed TSH supports the laboratory diagnosis of RTH. However, when RTH is mild and associated with thyroiditis, even a modest thyroid gland insufficiency can obliterate the serum T4 and T3 elevations, typical of RTH. This will manifest as elevated serum TSH. Demonstration of TRbeta gene mutation is then necessary to establish the diagnosis. In addition, under these circumstances, treatment with thyroid hormone should be considered.

Change in the amputation profile in diabetic foot in a tertiary reference center: efficacy of team working.

Diabetic foot is a serious complication of diabetes mellitus and the risk of lower extremity amputation is very high in this population when compared with people without diabetes. We have previously reported the lower-extremity amputation rate and significant factors in determining the risks for patients who had been admitted to Hacettepe University Hospital, a tertiary reference center for Turkey, between the years 1992 and 1996. In January 2000, a diabetic foot care team including an infectious diseases specialist, orthopaedic surgeons, endocrinologists, a plastic and reconstructive surgeon, a radiologist, and a diabetic foot nurse was assembled. To determine whether a change has occurred in the rate and the risk factors of lower extremity amputations after the establishment of this team, medical records of 66 patients (39 men, 27 women) with diabetic foot who had been admitted to Hacettepe University Hospital between 2000 and 2002 have now been retrospectively analysed. The grade distribution of diabetic foot according to Wagner classification was quite similar in the two studies (grade 1: 0 % vs. 4.5 %, grade 2: 15.6 % vs. 19.7 %, grade 3: 48 % vs. 33.3 %, grade 4: 24.4 % vs. 30.3 %, grade 5: 11.5 % vs. 12.1 % in the former and current study, respectively). The overall amputation rate in the current study was 39.4 % (36.7 % in the former study). Ray amputation (35 %) and below-knee amputations (30 %) were the two most commonly applied procedures. The rates of Syme, above knee, other amputations (i.e., Boyd, talonavicular amputations and partial calcanectomy) were 8 %, 8 % and 19 %, respectively. These data suggest that amputation is still a frequently encountered outcome for our patients with diabetic foot, but the amputation profile has changed. The implementation of a diabetic foot care team has relatively decreased the rate of major amputations in an attempt for limb salvage to improve the quality of life of the patients. Presence of osteomyelitis, peripheral vascular disease and gangrene still remain as significant predictors of amputation in our population.

Isolated metastasis of malignant melanoma into follicular carcinoma of the thyroid gland.

A 38-yr-old woman with a history of malignant melanoma (MM) presented with a thyroidal nodule. Fine needle aspiration biopsy of the thyroid was consistent with metastatic MM. The patient underwent thyroidectomy: microscopic examination revealed a follicular carcinoma nodule harboring a focus of metastatic melanoma. On review of the fine needle aspiration biopsy specimen, the population of cells with more uniform nuclei with focal follicle formation, which initially was interpreted as cells originating from normal thyroid tissue, was seen to actually represent the follicular carcinoma component. Tumor-to-tumor metastasis is an interesting phenomenon and there are only few cases of MM metastasis to other tumors. MM metastasis into a neoplastic thyroid nodule is a very rare combination and may be explained because the nodule in question represents the most highly vascularized component of the thyroid.

A patient presenting with spinal cord compression who had two distinct follicular cell type thyroid carcinomas.

A 61-yr-old woman presented with complaints of weakness and pain in her legs. A magnetic resonance imaging showed a 3 x 5.6 x 7.8 cm mass lesion destructing the T1 and T2 vertebral bodies and compressing the spinal cord. The mass was excised surgically. It was follicular carcinoma metastasis of the cervicodorsal region. Then, she underwent a total thyroidectomy. Pathological examination showed two different types of carcinomas in two different focuses; follicular carcinoma in the left lobe and follicular variant papillary carcinoma in the isthmic lobe. After the operation she was given 100 mCi 131I. This is the first report of a patient who had both metastatic follicular carcinoma and follicular variant papillary carcinoma together.

Effect of losartan on circulating TNFalpha levels and left ventricular systolic performance in patients with heart failure.

BACKGROUND: Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFalpha levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFalpha levels and ejection fraction (EF) in patients with congestive heart failure. METHODS: Forty patients with heart failure and EF < or = 40% were enrolled into the study. All of the patients have been given diuretic and digitalis therapy. Twenty patients were given losartan (50 mg/d) (Group I, 10 women, 10 men, 12 dilated cardiomyopathy, 8 ischemic heart disease, mean age 64.9 + 8.9), and another 20 patients were not given losartan because of hypotension or renal dysfunction (Group II, 13 men, 7 women, 10 dilated cardiomyopathy, 10 ischemic heart disease, mean age 61.2 +/- 10.5). EF was measured at the initial evaluation and on the fifteenth day of the therapy by echocardiographic examination using an acoustic quantification method. Circulating TNFalpha levels were also measured at the initial evaluation and on the fifteenth day of therapy by the ELISA method. RESULTS: Losartan significantly increased EF and decreased TNFalpha (EF increased from 29.4 +/- 7.3% to 36.0 +/- 8.5%, P < 0.001, and TNFalpha decreased from 39.2 +/- 37.4 pg/ml to 27.0 +/- 30.0 pg/ml, P < 0.05). Changes in TNFalpha levels and EF were not found to be correlated (r=-0.28, P=0.24). However, in the control group, EF and TNFalpha levels were similar at baseline and at the fifteenth day (EF 31.4 + 8.1% vs 31.7 +/- 7.8%, P=0.1, and TNFalpha 91.5 + 86.0 pg/ml vs 110.0 +/- 80.7 pg/ml, P=0.1, respectively). CONCLUSIONS: Losartan improves left ventricular systolic function and decreases TNFalpha level. The decreased TNFalpha level seems to be independent of EF.

Indications for immediate tissue transfer for soft tissue reconstruction in visceral pelvic surgery.

BACKGROUND: Perineal wound complications may occur after visceral pelvic surgery. We reviewed our experience to determine indications for immediate tissue transfer (TT) to prevent complications. METHODS: Hospital records and computerized data were reviewed on 175 perineal repairs in 156 patients treated at The University of Texas M.D. Anderson Cancer Center for tumors involving the alimentary tract (135 of 175), genitourinary tract (15 of 175), perineum (19 of 175), or sacrum (6 of 175). Patients had either resection of only the colorectum and anus (APR) (46 of 175) or multivisceral resection (MVR) (129 of 175), and the perineal wound was closed by using TT (108 of 175) or primary closure (PC) (67 of 175) on the basis of the surgeon's judgment. Complications were compared between PC and TT groups. RESULTS: Complications occurred in 57% (100 of 175). There was no significant difference overall in PC and TT procedures or in the APR subgroup. There were significantly fewer complications for TT patients in the MVR subgroup (P =.0001). There were significantly fewer complications for TT patients with prior irradiation in both APR (P =.01) and MVR (P =.007) subgroups. CONCLUSIONS: Immediate TT for perineal wound closure is associated with fewer healing complications than PC in a subset of patients with multivisceral resection or prior radiotherapy. Surgical planning in these cases should consider immediate soft tissue reconstruction.

Endogenous sex steroid, GH and IGF-I levels in normal elderly men: relationships with bone mineral density and markers of bone turnover.

There are studies concerning the association among endogenous sex steroids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) in both men and women. However, little is known concerning the association of these parameters with markers of bone turnover in healthy elderly men. We studied the association of BMD (dual energy X-ray absorptiometry of spine, hip and forearm) and markers of bone turnover (bone-specific alkaline phosphatase, serum C-terminal propeptide of type I collagen, and serum osteocalcin reflecting formation, urine deoxypyridinoline and calcium excretion in relation to creatinine excretion reflecting resorption) with endogenous sex steroids, GH and IGF-I in 14 elderly normal men (age range 60-79 years). There was a negative correlation between age and dehydroepiandrosterone sulphate (DHEAS) (r=-0.60, p=0.022) and a positive correlation between GH and IGF-I (r=0.53, p=0.048). Serum estradiol concentrations correlated with BMD at distal 1/3 radius (r=0.41, p=0.1) and mid-radius (r=0.47, p=0.08), and negatively correlated with age (r=-0.45, p=0.09). There was no correlation of estradiol with bone turnover markers, testosterone, free testosterone, DHEAS, GH and IGF-I. Serum GH and IGF-I levels showed no correlation with BMD (all sites) and bone turnover markers. Serum total testosterone concentrations positively correlated with BMD at distal 1/3 radius (r=0.47, p=0.09), femoral neck (r=0.56, p=0.037) and Ward's triangle (r=0.49, p=0.07). These data suggest that serum estradiol and testosterone levels are associated with BMD in elderly men, possibly indicating their contribution to skeletal maintenance in old age. However, correlations of IGF-I, GH and DHEAS with BMD and bone turnover markers are lacking in the group studied.

Isolated adrenocorticotropic hormone deficiency, thyroid autoimmunity, and transient hyperprolactinemia.

OBJECTIVE: To describe a case of isolated adrenocorticotropic hormone (ACTH) deficiency associated with thyroid autoimmunity, subclinical hypothyroidism, and transient hyperprolactinemia. METHODS: We present a detailed case report, including results of laboratory studies and magnetic resonance imaging, and discuss potential contributing factors in this setting. RESULTS: In a 23-year-old woman with isolated ACTH deficiency accompanied by thyroid autoimmunity (Hashimoto's thyroiditis), subclinical primary hypothyroidism, and hyperprolactinemia, magnetic resonance imaging of the pituitary showed normal findings but dynamic stimulation testing of the pituitary gland indicated an isolated ACTH deficiency with intact growth hormone and gonadotropin secretory reserves. The cortisol response to the short ACTH stimulation test was subnormal. Therapy with prednisolone (5 mg/day) and levothyroxine (100 microg/day) was initiated. Results of thyroid function tests were normalized after 1 month, the prolactin level decreased to normal after 1 year, and titers of thyroid autoantibodies decreased substantially after 1.5 years of treatment. CONCLUSION: The correction of the related glucocorticoid deficiency resulted in resolution of the hyperprolactinemia and a decrease in titers of thyroid autoantibodies.