Distribution and release of human pancreatic polypeptide.

PubMed Central

Adrian, T E; Bloom, S R; Bryant, M G; Polak, J M; Heitz, P H; Barnes, A J

1976-01-01

A simple and reliable radioimmunoassay has been developed for a new gut hormone, HPP. In the primate 93% of the total PP was found in the pancreas with a small amount throughout the remaining gastrointestinal tract. HPP has been shown to be produced by a number of pancreatic apudomas and their metastases. The immunoreactive PP from these tumours and from normal pancreas was chromatographically indistinguishable from the pure peptide. The plasma PP concentration rose rapidly after a meal in normal subjects and was still raised six hours later. Fasting plasma PP levels in patients with PP cell containing pancreatic endocrine tumours were higher than even the postprandial level in normal subjects. PP measurements is thus useful in diagnosis of pancreatic endocrine tumours. Images Fig. 2 PMID:828120

Lifestyle intervention and/or statins for the reduction of C-reactive Protein in Type 2 diabetes: From the Look AHEAD Study

USDA-ARS?s Scientific Manuscript database

Objective: Cardiovascular risk remains high despite statin use. Overweight/obese diabetic persons usually have normal/low LDL-cholesterol but high C-reactive protein (CRP) levels. We aimed to examine the effects of intensive lifestyle intervention for weight loss (ILI) on CRP levels in overweight/ob...

Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood.

PubMed

Mesman, Esther; Hillegers, Manon Hj; Ambree, Oliver; Arolt, Volker; Nolen, Willem A; Drexhage, Hemmo A

2015-02-01

There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder. Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls. During adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages. This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Normal Human Fibroblasts Are Resistant to RAS-Induced Senescence

PubMed Central

Benanti, Jennifer A.; Galloway, Denise A.

2004-01-01

Oncogenic stimuli are thought to induce senescence in normal cells in order to protect against transformation and to induce proliferation in cells with altered p53 and/or retinoblastoma (Rb) pathways. In human fibroblasts, RAS initiates senescence through upregulation of the cyclin-dependent kinase inhibitor p16INK4A. We show here that in contrast to cultured fibroblast strains, freshly isolated normal fibroblasts are resistant to RAS-induced senescence and instead show some characteristics of transformation. RAS did not induce growth arrest or expression of senescence-associated β-galactosidase, and Rb remained hyperphosphorylated despite elevated levels of p16. Instead, RAS promoted anchorage-independent growth of normal fibroblasts, although expression of hTert with RAS increased colony formation and allowed normal fibroblasts to bypass contact inhibition. To test the hypothesis that p16 levels determine how cells respond to RAS, we expressed RAS in freshly isolated fibroblasts that expressed very low levels of p16, in hTert-immortalized fibroblasts that had accumulated intermediate levels of p16, and in IMR90 fibroblasts with high levels of p16. RAS induced growth arrest in cells with higher p16 levels, and this effect was reversed by p16 knockdown in the hTert-immortalized fibroblasts. These findings indicate that culture-imposed stress sensitizes cells to RAS-induced arrest, whereas early passage cells do not arrest in response to RAS. PMID:15024073

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

PubMed Central

Nathwani, Amit C.; Tuddenham, Edward G.D.; Rangarajan, Savita; Rosales, Cecilia; McIntosh, Jenny; Linch, David C.; Chowdary, Pratima; Riddell, Anne; Pie, Arnulfo Jaquilmac; Harrington, Chris; O’Beirne, James; Smith, Keith; Pasi, John; Glader, Bertil; Rustagi, Pradip; Ng, Catherine Y.C.; Kay, Mark A.; Zhou, Junfang; Spence, Yunyu; Morton, Christopher L.; Allay, James; Coleman, John; Sleep, Susan; Cunningham, John M.; Srivastava, Deokumar; Basner-Tschakarjan, Etiena; Mingozzi, Federico; High, Katherine A.; Gray, John T.; Reiss, Ulrike M.; Nienhuis, Arthur W.; Davidoff, Andrew M.

2012-01-01

BACKGROUND Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. METHODS We infused a single dose of a serotype-8–pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values). Study participants were enrolled sequentially in one of three cohorts (given a high, intermediate, or low dose of vector), with two participants in each group. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. RESULTS AAV-mediated expression of FIX at 2 to 11% of normal levels was observed in all participants. Four of the six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other two, the interval between prophylactic injections was increased. Of the two participants who received the high dose of vector, one had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid–specific T cells in the peripheral blood; the other had a slight increase in liver-enzyme levels, the cause of which was less clear. Each of these two participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained FIX levels in the range of 3 to 11% of normal values. CONCLUSIONS Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.) PMID:22149959

Dorsal aorta catheterization in rainbow trout (Salmo gairdneri) I. Its validity in the study of blood gonadotropin patterns.

PubMed

Zohar, Y

1980-01-01

The use of a dorsal aorta catheterization technique to study gonadotropin secretion patterns in the rainbow trout was tested. Heparin used to flush the cannula between repetitive samplings did not have any effect on plasma GTH levels. Catheterization resulted in a slight short-term change in those levels. The gonadotropin levels returned to their initial values as soon as 30 min to 6 hrs after the operation. From then on, the GTH levels remained close to the initial values in fish exhibiting normal feeding behaviour, whereas they tended to decrease in "stressed" females which did not eat normally. The fish which adapted well to dorsal aortic catheterization did not show any changes in the diurnal pattern of GTH levels or in normal gonadal function and GTH profiles during the processes of oocyte maturation and ovulation. It is concluded that individual catheterized trout can be used advantageously for studying gonadotropin secretion patterns after a 3-day recovery period and the elimination of those fish which neither resume normal feeding nor return to initial, pre-operative GTH levels. Using this technique, it was demonstrated that hypophysial GTH release in trout with oocytes undergoing active vitellogenesis is probably effected by short-term bursts (pulses) of secretion.

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

PubMed Central

Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

2013-01-01

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. PMID:23459235

Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells.

PubMed

Ke, Jia; Zhao, Zhiju; Hong, Su-Hyung; Bai, Shoumin; He, Zhen; Malik, Fayaz; Xu, Jiahui; Zhou, Lei; Chen, Weilong; Martin-Trevino, Rachel; Wu, Xiaojian; Lan, Ping; Yi, Yongju; Ginestier, Christophe; Ibarra, Ingrid; Shang, Li; McDermott, Sean; Luther, Tahra; Clouthier, Shawn G; Wicha, Max S; Liu, Suling

2015-02-28

Increasing evidence suggests that lineage specific subpopulations and stem-like cells exist in normal and malignant breast tissues. Epigenetic mechanisms maintaining this hierarchical homeostasis remain to be investigated. In this study, we found the level of microRNA221 (miR-221) was higher in stem-like and myoepithelial cells than in luminal cells isolated from normal and malignant breast tissue. In normal breast cells, over-expression of miR-221 generated more myoepithelial cells whereas knock-down of miR-221 increased luminal cells. Over-expression of miR-221 stimulated stem-like cells in luminal type of cancer and the miR-221 level was correlated with clinical outcome in breast cancer patients. Epithelial-mesenchymal transition (EMT) was induced by overexpression of miR-221 in normal and breast cancer cells. The EMT related gene ATXN1 was found to be a miR-221 target gene regulating breast cell hierarchy. In conclusion, we propose that miR-221 contributes to lineage homeostasis of normal and malignant breast epithelium.

Severe Hypertriglyceridemia Possibly Masked Acute Pancreatitis and Led to a Difficult Diagnosis in an Obese Patient with Ketoacidosis-onset Type 2 Diabetes.

PubMed

Fujishiro, Midori; Horita, Akiko; Nakagawara, Hiroshi; Mawatari, Takayuki; Kishigami, Yoshifusa; Tominaga, Yoshiteru; Moriyama, Mitsuhiko; Ishihara, Hisamitsu

2017-10-01

A young obese man with ketoacidosis-onset type 2 diabetes mellitus, associated with severe hypertriglyceridemia, was admitted to a local hospital complaining of abdominal pain. Although the abdominal pain worsened, his serum amylase level remained normal with persistent severe hypertriglyceridemia until the second day of hospitalization. The next day, computed tomography showed severe acute pancreatitis (AP) with serum amylase elevation, while the patient's triglyceride level decreased to 558 mg/dL. He was transferred to our hospital and recovered after intensive care. AP accompanied by diabetic ketoacidosis is not rare but an early diagnosis can be difficult to make due to normal amylase levels in the presence of severe hypertriglyceridemia.

Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors.

PubMed Central

Rana, B; Mischoulon, D; Xie, Y; Bucher, N L; Farmer, S R

1994-01-01

Previous investigations have shown that culture of freshly isolated hepatocytes under conventional conditions, i.e., on dried rat tail collagen in the presence of growth factors, facilitates cell growth but also causes an extensive down-regulation of most liver-specific functions. This dedifferentiation process can be prevented if the cells are cultured on a reconstituted basement membrane gel matrix derived from the Englebreth-Holm-Swarm mouse sarcoma tumor (EHS gel). To gain insight into the mechanisms regulating this response to extracellular matrix, we are analyzing the activities of two families of transcription factors, C/EBP and AP-1, which control the transcription of hepatic and growth-responsive genes, respectively. We demonstrate that isolation of hepatocytes from the normal quiescent rat liver by collagenase perfusion activates the immediate-early growth response program, as indicated by increased expression of c-jun, junB, c-fos, and c-myc mRNAs. Adhesion of these activated cells to dried rat tail collagen augments the elevated levels of these mRNAs for the initial 1 to 2 h postplating; junB and c-myc mRNA levels then drop steeply, with junB returning to normal quiescence and the c-myc level remaining slightly elevated during the 3-day culture period. Levels of c-jun mRNA and AP-1 DNA binding activity, however, remain elevated from the outset, while C/EBP alpha mRNA expression is down-regulated, resulting in a decrease in the steady-state levels of the 42- and 30-kDa C/EBP alpha polypeptides and C/EBP alpha DNA binding activity. In contrast, C/EBP beta mRNA production remains at near-normal hepatic levels for 5 to 8 days of culture, although its DNA binding activity decreases severalfold during this time. Adhesion of hepatocytes to the EHS gel for the same period of time dramatically alters this program: it arrests growth and inhibits AP-1 DNA binding activity and the expression of c-jun, junB, and c-myc mRNAs, but, in addition, it restores C/EBP alpha mRNA and protein as well as C/EBP alpha and C/EBP beta DNA binding activities to the abundant levels present in freshly isolated hepatocytes. These changes are not due merely to growth inhibition, because suppression of hepatocyte proliferation on collagen by epidermal growth factor starvation or addition of transforming growth factor beta does not inhibit AP-1 activity or restore C/EBP alpha DNA binding activity to normal hepatic levels. These data suggest that expression of the normal hepatic phenotype requires that hepatocytes exist in a G0 state of growth arrest, facilitated here by adhesion of cells to the EHS gel, in order to express high levels of hepatic transcription factors such as C/EBP alpha. Images PMID:8065319

Use of liothyronine without levothyroxine in the treatment of mild consumptive hypothyroidism caused by hepatic hemangiomas.

PubMed

Higuchi, Shinji; Takagi, Masaki; Hasegawa, Yukihiro

2017-06-29

There have been reports of the use of levothyroxine or levothyroxine plus liothyronine for consumptive hypothyroidism caused by hepatic hemangiomas. Administration of levothyroxine without liothyronine can be inadequate to maintain normal levels of both free T3 and free T4 in some patients. However, there is no report of treatment with liothyronine plus propranolol. We herein present a case in which we used liothyronine therapy for multifocal hepatic hemangiomas in a Japanese patient with low free T3 and normal free T4 levels. A 2-month-old Japanese male was referred to our hospital because of jaundice. Abdominal computed tomography showed multifocal hemangiomas in both lobes of the liver. TSH level was elevated, free T3 level was low, free T4 level was normal, and hypothyroidism due to hepatic hemangiomas was diagnosed. In addition to propranolol, liothyronine was started. We used liothyronine without levothyroxine for hypothyroidism because only free T3 level had decreased, whereas free T4 level remained in the normal range. The TSH and free T3 levels normalized in this patient in less than 1 month. The liothyronine dose was gradually reduced with regression of the hemangiomas, and liothyronine administration was discontinued at the age of 5 months. At the age of 11 months, growth and neurological development of the patient met age-specific norms, and he was euthyroid at that time. This is the first report demonstrating the use of liothyronine with propranolol for treatment of this type of consumptive hypothyroidism.

Hypocomplementemia is associated with worse renal survival in ANCA-positive granulomatosis with polyangiitis and microscopic polyangiitis

PubMed Central

Aouba, Achille; Khoy, Kathy; Mariotte, Delphine; Lobbedez, Thierry; Martin Silva, Nicolas

2018-01-01

Recent data suggest the existence of a complement alternative pathway activation in the pathogenesis of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a condition that remains poorly understood. This study aims to assess the clinical characteristics and outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with regard to their plasma complement levels at diagnosis. A retrospective monocentric study carried out at Caen University Hospital led to the identification of proteinase-3- or myeloperoxidase-ANCA-positive GPA and MPA patients from January 2000 to June 2016 and from September 2011 to June 2016, respectively. All patients with available C3 and C4 levels at diagnosis were included. Patients were categorized in the hypocomplementemia group if their C3 and/or C4 levels at diagnosis were below the lower limit of the normal range. Among the 76 AAV patients (43 GPA, 33 MPA), 4 (5%) had hypocomplementemia, and the 72 remaining patients exhibited normal plasma complement levels. All 4 hypocomplementemia patients had renal involvement. Hypocomplementemia was followed in 1 patient whose post-treatment complement level normalized within 1 month. Among all clinical and ANCA specificity, including relapse-free survival (p = 0.093), only overall and renal survival rates were significantly lower in the hypocomplementemia group (p = 0.0011 and p<0.001, respectively). Hypocomplementemia with low C3 and/or C4 levels at GPA or MPA diagnosis may be responsible for worse survival and renal prognosis. These results argue for larger and prospective studies to better determine the epidemiology of the disease and to assess complement-targeting therapy in these patients. PMID:29621352

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis.

PubMed

Vallota, E H; Forristal, J; Spitzer, R E; Davis, N C; West, C D

1971-03-01

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

SET8 is involved in the regulation of hyperglycemic memory in human umbilical endothelial cells.

PubMed

Chen, Xiangyuan; Wu, Qichao; Jiang, Hui; Wang, Jiaqiang; Zhao, Yanjun; Xu, Yajun; Zhu, Minmin

2018-05-14

Hyperglycemic memory occurs in diabetic cardiovascular complications, but the underlying mechanism remains to be elucidated. Although the depletion of SET8 leads to increased mitochondrial oxidative stress via increasing cellular reactive oxygen species (ROS) production, the role of SET8 in hyperglycemic memory-induced mitochondrial dysfunction is not well understood. Here, we investigated the role of SET8 in this setting. Our results showed that high glucose-induced vascular inflammation, ROS production and apoptosis remained at high levels even when glucose returned to normal level. Elevated glucose reduced SET8 expression, which also remained at low level after returning to normoglycemia. SET8 overexpression protected cells from elevated glucose and hyperglycemic memory-induced endothelial injury by blocking ROS accumulation, attenuating vascular inflammation, and restoring nitric oxide production. Thus, our results suggest that SET8 may be a key mediator in hyperglycemic memory.

RED BLOOD CELL PRESERVATION.

DTIC Science & Technology

red cells were assayed by ion exchange chromatography. The O-day 2,3- diphosphoglycerate concentrations of the ACD-AP bloods were below the normal...adenosine or guanosine. After a small initial increase, the ADP levels remained fairly constant. The AMP values increased as the ATP decreased and in

Radiofrequency Ablation Followed by Percutaneous Ethanol Ablation Leading to Long-Term Remission of Hyperparathyroidism

PubMed Central

Menon, Arun S.; Nazar, P. K.; Moorthy, Srikanth; Kumar, Harish; Nair, Vasantha; Pavithran, Praveen Valiyaparambil; Bhavani, Nisha; Menon, Vadayath Usha; Abraham, Nithya; Jayakumar, R. Vasukutty

2017-01-01

A 30-year-old male with cerebral palsy and motor impairment presented with right femur fracture. He had gradually worsening mobility and contractures of all extremities for the preceding 5 years. Evaluation showed multiple vertebral and femoral fractures, severe osteoporosis, a large parathyroid adenoma, and parathormone (PTH) exceeding 2500 pg/mL. Because of poor general health and high anesthetic risk, parathyroidectomy was deemed impractical. Ultrasound-guided radiofrequency ablation (RFA) helped achieve 50% size reduction and PTH levels with better control of hypercalcemia. Later, as calcium and PTH remained elevated, percutaneous ethanol ablation was performed with resultant normalization of PTH and substantial symptomatic improvement. Two years later, he still remains normocalcaemic with normal PTH levels. We propose that RFA and percutaneous ethanol ablation be considered as effective short-term options for surgically difficult cases, which could even help achieve long-term remission. Although not previously reported, our case illustrates that both RFA and percutaneous ethanol ablation could be safely performed successively achieving long-term remission. PMID:29264521

Variability in monthly serum bicarbonate measures in hemodialysis patients: a cohort study.

PubMed

Patel, Ravi; Paredes, William; Hall, Charles B; Nader, Mark A; Sapkota, Deepak; Folkert, Vaughn W; Abramowitz, Matthew K

2015-12-21

Some nephrologists have advocated an individualized approach to the prescription of bicarbonate hemodialysis. However, the utility of monthly serum bicarbonate levels for guiding and evaluating such treatment decisions has not been evaluated. We sought to define the variability of these measurements and to determine factors that are associated with month-to-month variability in pre-dialysis serum bicarbonate. We examined the monthly variability in serum bicarbonate measurements among 181 hemodialysis patients admitted to a free-standing dialysis unit in the Bronx, NY from 1/1/2008-6/30/2012. All patients were treated with a uniform bicarbonate dialysis prescription (bicarbonate 35 mEq/L, acetate 8 mEq/L). Pre-dialysis serum bicarbonate values were obtained from monthly laboratory reports. Month-to-month variability was defined using a rolling measurement for each time point. Only 34 % of high serum bicarbonate values (>26 mEq/L) remained high in the subsequent month, whereas 60 % converted to normal (22-26 mEq/L). Of all low values (<22 mEq/L), 41 % were normal the following month, while 58 % remained low. Using the mean 3-month bicarbonate, only 29 % of high values remained high in the next 3-month period. In multivariable-adjusted longitudinal models, both low and high serum bicarbonate values were associated with greater variability than were normal values (β = 0.12 (95 % CI 0.09-0.15) and 0.24 (0.18 to 0.29) respectively). Variability decreased with time, and was significantly associated with age, phosphate binder use, serum creatinine, potassium, and normalized protein catabolic rate. Monthly pre-dialysis serum bicarbonate levels are highly variable. Even if a clinician takes no action, approximately 50 % of bicarbonate values outside a normal range of 22-26 mEq/L will return to normal in the subsequent month. The decision to change the bicarbonate dialysis prescription should not be based on a single bicarbonate value, and even a 3-month mean may be insufficient.

A case of sibutramine-induced hyperprolactinemia.

PubMed

Soares Leaes, Carolina Garcia; Pereira-Lima, Júlia Fernanda Semmelmann; da Costa Oliveira, Miriam

2011-01-01

Several drugs may cause hyperprolactinemia, especially antipsychotic drugs and prokynetic drugs. Serum prolactin concentrations increase within hours after acute administration of these drugs and return to normal within two to four days after cessation of chronic therapy. So far, sibutramine, a sympathomimetic drug used in the management of obesity, was not described to be associated with altered prolactin levels. The purpose of this study is to present a case of sibutramine-induced hiperprolactinemia. A 38-year-old white female patient seeks medical attention complaining of weight gain (Body mass index: 35) associated with anxiety. She started sibutramine treatment and presented with amenogalactorrhea. Hyperprolactinemia was diagnosed (prolactin of 46 and 89.6 ng/mL) with normal thyroid, renal and hepatic function, and a negative pregnancy test. A sella MRI was performed and sibutramine was suspended. Prolactin levels returned to normal within 15 days of sibutramine cessation and remained normal within 90 days of follow-up, with resolution of the amenogalactorrhea syndrome. sibutramine may be considered in differential diagnosis of drug-induced hyperprolactinemia.

Unravelling the influence of mild traumatic brain injury (MTBI) on cognitive-linguistic processing: a comparative group analysis.

PubMed

Barwood, Caroline H S; Murdoch, Bruce E

2013-06-01

Cognitive-linguistic deficits often accompany traumatic brain injury (TBI) and can negatively impact communicative competency. The linguistic sequelae underpinning mild TBI (MTBI) remain largely unexplored in contemporary literature. The present research methods aim to provide group evidence pertaining to the influence of MTBI on linguistic and higher-level language processing. Extrapolating on the findings of recent case reports, it is hypothesized that performance of the MTBI patients will be significantly reduced compared to normal controls performance on the employed high-level linguistic tasks. Sixteen patients with MTBI and 16 age- and education-matched normal control participants were assessed using a comprehensive battery of cognitive-linguistic assessments. The results demonstrated statistically significant differences between MTBI and normal control group performance across a number of higher-level linguistic, general cognitive and general language tasks. MTBI group performance was significantly lower than the normal control group on tasks requiring complex lexical semantic operations and memory demands, including: Recall, organization, making inferences, naming and perception/discrimination. These outcomes confer that post-MTBI, cognitive, high-level language and isolated general language performance (e.g. naming) is significantly reduced in MTBI patients, compared to normal controls. Furthermore, the detailed cognitive-linguistic profile offered provides a necessary direction for the identification of areas of linguistic decline in MTBI and targets for therapeutic intervention of impaired cognitive-linguistic processes to ultimately improve communicative outcomes in MTBI.

Towards black-box calculations of tunneling splittings obtained from vibrational structure methods based on normal coordinates.

PubMed

Neff, Michael; Rauhut, Guntram

2014-02-05

Multidimensional potential energy surfaces obtained from explicitly correlated coupled-cluster calculations and further corrections for high-order correlation contributions, scalar relativistic effects and core-correlation energy contributions were generated in a fully automated fashion for the double-minimum benchmark systems OH3(+) and NH3. The black-box generation of the potentials is based on normal coordinates, which were used in the underlying multimode expansions of the potentials and the μ-tensor within the Watson operator. Normal coordinates are not the optimal choice for describing double-minimum potentials and the question remains if they can be used for accurate calculations at all. However, their unique definition is an appealing feature, which removes remaining errors in truncated potential expansions arising from different choices of curvilinear coordinate systems. Fully automated calculations are presented, which demonstrate, that the proposed scheme allows for the determination of energy levels and tunneling splittings as a routine application. Copyright © 2013 Elsevier B.V. All rights reserved.

Ablation of TrkB expression in RGS9-2 cells leads to hyperphagic obesity★

PubMed Central

Liao, Guey-Ying; Li, Yuqing; Xu, Baoji

2013-01-01

Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB (tropomyosin receptor kinase B), are widely expressed in the brain where they regulate a wide variety of biological processes, including energy homeostasis. However, the specific population(s) of TrkB-expressing neurons through which BDNF governs energy homeostasis remain(s) to be determined. Using the Cre-loxP recombination system, we deleted the mouse TrkB gene in RGS9-2-expressing cells. In this mouse mutant, TrkB expression was abolished in several hypothalamic nuclei, including arcuate nucleus, dorsomedial hypothalamus, and lateral hypothalamus. TrkB expression was also abolished in a small number of cells in other brain regions, including the cerebral cortex and striatum. The mutant animals developed hyperphagic obesity with normal energy expenditure. Despite hyperglycemia under fed conditions, these animals exhibited normal fasting blood glucose levels and normal glucose tolerance. These results suggest that BDNF regulates energy homeostasis in part through TrkB-expressing neurons in the hypothalamus. PMID:24327964

Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice

PubMed Central

Nakai, Nobuhiro; Nagano, Masatoshi; Saitow, Fumihito; Watanabe, Yasuhito; Kawamura, Yoshinobu; Kawamoto, Akiko; Tamada, Kota; Mizuma, Hiroshi; Onoe, Hirotaka; Watanabe, Yasuyoshi; Monai, Hiromu; Hirase, Hajime; Nakatani, Jin; Inagaki, Hirofumi; Kawada, Tomoyuki; Miyazaki, Taisuke; Watanabe, Masahiko; Sato, Yuka; Okabe, Shigeo; Kitamura, Kazuo; Kano, Masanobu; Hashimoto, Kouichi; Suzuki, Hidenori; Takumi, Toru

2017-01-01

Serotonin is a critical modulator of cortical function, and its metabolism is defective in autism spectrum disorder (ASD) brain. How serotonin metabolism regulates cortical physiology and contributes to the pathological and behavioral symptoms of ASD remains unknown. We show that normal serotonin levels are essential for the maintenance of neocortical excitation/inhibition balance, correct sensory stimulus tuning, and social behavior. Conversely, low serotonin levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication) result in impairment of the same phenotypes. Restoration of normal serotonin levels in 15q dup mice revealed the reversibility of a subset of ASD-related symptoms in the adult. These findings suggest that serotonin may have therapeutic potential for discrete ASD symptoms. PMID:28691086

Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

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

Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki

2011-01-07

Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response ofmore » normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 mRNA levels significantly declined following irradiation (p < 0.01), whereas Bnip3 levels increased. Conclusions: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. Whether this is due to defective maturation or to aberrant degradation of the autophagosomes requires further investigation.« less

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs.

PubMed

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = -19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

PubMed Central

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

Objective To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. Methods In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. Results 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average −4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = −19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Conclusion Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. PMID:27454447

Summary and statistical analysis of precipitation and groundwater data for Brunswick County, North Carolina, Water Year 2008

USGS Publications Warehouse

McSwain, Kristen Bukowski; Strickland, A.G.

2010-01-01

Groundwater conditions in Brunswick County, North Carolina, have been monitored continuously since 2000 through the operation and maintenance of groundwater-level observation wells in the surficial, Castle Hayne, and Peedee aquifers of the North Atlantic Coastal Plain aquifer system. Groundwater-resource conditions for the Brunswick County area were evaluated by relating the normal range (25th to 75th percentile) monthly mean groundwater-level and precipitation data for water years 2001 to 2008 to median monthly mean groundwater levels and monthly sum of daily precipitation for water year 2008. Summaries of precipitation and groundwater conditions for the Brunswick County area and hydrographs and statistics of continuous groundwater levels collected during the 2008 water year are presented in this report. Groundwater levels varied by aquifer and geographic location within Brunswick County, but were influenced by drought conditions and groundwater withdrawals. Water levels were normal in two of the eight observation wells and below normal in the remaining six wells. Seasonal Kendall trend analysis performed on more than 9 years of monthly mean groundwater-level data collected in an observation well located within the Brunswick County well field indicated there is a strong downward trend, with water levels declining at a rate of about 2.2 feet per year.

Calcium Metabolism in Newborn Infants THE INTERRELATIONSHIP OF PARATHYROID FUNCTION AND CALCIUM, MAGNESIUM, AND PHOSPHORUS METABOLISM IN NORMAL, “SICK,” AND HYPOCALCEMIC NEWBORNS

PubMed Central

David, Louis; Anast, Constantine S.

1974-01-01

Serum immunoreactive parathyroid hormone (iPTH) and plasma total calcium, ionized calcium, magnesium, and phosphorus levels were determined during the first 9 days of life in 137 normal term infants, 55 “sick” infants, and 43 hypocalcemic (Ca <7.5 mg/100 ml; Ca++<4.0 mg/100 ml) infants. In the cord blood, elevated levels of plasma Ca++ and Ca were observed, while levels of serum iPTH were either undetectable or low. In normal newborns during the first 48 h of life there was a decrease in plasma Ca and Ca++, while the serum iPTH level in most samples remained undetectable or low; after 48 h there were parallel increases in plasma Ca and Ca++ and serum iPTH levels. Plasma Mg and P levels increased progressively after birth in normal infants. In the sick infants, plasma Ca, Ca++ and P levels were significantly lower than in the normal newborns, while no significant differences were found in the plasma Mg levels. The general pattern of serum iPTH levels in the sick infants was similar to that observed in the normal group, though there was a tendency for the increase in serum iPTH to occur earlier and for the iPTH levels to be higher in the sick infants. In the hypocalcemic infants, plasma Mg levels were consistently lower than in the normal infants after 24 h of age, while no significant differences were found in the plasma P levels. Hyperphosphatemia was uncommon and did not appear to be a contributing factor in the pathogenesis of hypocalcemia in most infants. Most of the hypocalcemic infants, including those older than 48 h, had inappropriately low serum iPTH levels. Evidence obtained from these studies indicates that parathyroid secretion is normally low in the early new born period and impaired parathyroid function, characterized by undetectable or low serum iPTH, is present in most infants with neonatal hypocalcemia. Additional unknown factors appear to contribute to the lowering of plasma Ca in the neonatal period. The net effect of unknown plasma hypocalcemic factor(s) on the one hand and parathyroid activity on the other may account for differences in plasma Ca levels observed between normal, sick, and hypocalcemic infants. Depressed plasma Mg is frequently present in hypocalcemic infants. To what degree the hypomagnesemia reflects parathyroid insufficiency or the converse, to what degree parathyroid insufficiency and hypocalcemia are secondary to hypomagnesemia, is uncertain. PMID:4858778

Gene expression of regulatory enzymes of glycolysis/gluconeogenesis in regenerating rat liver.

PubMed Central

Rosa, J L; Bartrons, R; Tauler, A

1992-01-01

Levels of mRNA for glucokinase, L-pyruvate kinase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase were analysed during liver regeneration. Levels of mRNA for glycolytic enzymes (glucokinase and L-pyruvate kinase) decreased rapidly after partial hepatectomy. Glucokinase mRNA increased at 16-24 h, returning to normal values after this time. L-pyruvate kinase mRNA recovered control levels at 168 h. In contrast, phosphoenolpyruvate carboxykinase mRNA increased rapidly after liver resection and remained high during the regenerative process. However, the levels of fructose-1,6-bisphosphatase mRNA were not modified significantly. These results correlate with the reported increased rate of gluconeogenesis and changes in enzyme levels after partial hepatectomy. The effect of stress on the mRNA levels was also studied. All enzymes showed variations in their mRNA levels after the surgical stress. In general, the differences were more pronounced in regenerating liver than in sham-operated animals, being practically normalized at 24 h. Images Fig. 2. Fig. 3. PMID:1329724

Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

PubMed Central

Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

2013-01-01

Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

Comparative analysis of neural network and regression based condition monitoring approaches for wind turbine fault detection

NASA Astrophysics Data System (ADS)

Schlechtingen, Meik; Ferreira Santos, Ilmar

2011-07-01

This paper presents the research results of a comparison of three different model based approaches for wind turbine fault detection in online SCADA data, by applying developed models to five real measured faults and anomalies. The regression based model as the simplest approach to build a normal behavior model is compared to two artificial neural network based approaches, which are a full signal reconstruction and an autoregressive normal behavior model. Based on a real time series containing two generator bearing damages the capabilities of identifying the incipient fault prior to the actual failure are investigated. The period after the first bearing damage is used to develop the three normal behavior models. The developed or trained models are used to investigate how the second damage manifests in the prediction error. Furthermore the full signal reconstruction and the autoregressive approach are applied to further real time series containing gearbox bearing damages and stator temperature anomalies. The comparison revealed all three models being capable of detecting incipient faults. However, they differ in the effort required for model development and the remaining operational time after first indication of damage. The general nonlinear neural network approaches outperform the regression model. The remaining seasonality in the regression model prediction error makes it difficult to detect abnormality and leads to increased alarm levels and thus a shorter remaining operational period. For the bearing damages and the stator anomalies under investigation the full signal reconstruction neural network gave the best fault visibility and thus led to the highest confidence level.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

PubMed

Osman, Faizel; Franklyn, Jayne A; Daykin, Jacqueline; Chowdhary, Saqib; Holder, Roger L; Sheppard, Michael C; Gammage, Michael D

2004-08-15

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways

PubMed Central

Naqvi, Shaista; Zhu, Changfu; Farre, Gemma; Ramessar, Koreen; Bassie, Ludovic; Breitenbach, Jürgen; Perez Conesa, Dario; Ros, Gaspar; Sandmann, Gerhard; Capell, Teresa; Christou, Paul

2009-01-01

Vitamin deficiency affects up to 50% of the world's population, disproportionately impacting on developing countries where populations endure monotonous, cereal-rich diets. Transgenic plants offer an effective way to increase the vitamin content of staple crops, but thus far it has only been possible to enhance individual vitamins. We created elite inbred South African transgenic corn plants in which the levels of 3 vitamins were increased specifically in the endosperm through the simultaneous modification of 3 separate metabolic pathways. The transgenic kernels contained 169-fold the normal amount of β-carotene, 6-fold the normal amount of ascorbate, and double the normal amount of folate. Levels of engineered vitamins remained stable at least through to the T3 homozygous generation. This achievement, which vastly exceeds any realized thus far by conventional breeding alone, opens the way for the development of nutritionally complete cereals to benefit the world's poorest people. PMID:19416835

Halitosis as a product of hepatic disease.

PubMed

Guglielmi, M; Beushausen, M; Feng, C; Beech, A; Baur, D

2014-09-01

This study evaluated halitosis in patients suffering from hepatic disease. Twenty-five patients (12 males and 13 females) aged between 16 and 73 years who had undergone treatment for liver disease were included in this study. Three halimeter recordings were performed to measure methyl mercarptan and hydrogen sulphite. Mean values were calculated and compared with normal values (75-120 ppb). The level of significance was set at P < .05. Results: Thirteen of the 25 subjects (52%) had normal Volatile Sulphur Compound (VSC) values (75-120 ppb). Twelve subjects (48%) recorded values ranging from 132 to 1112 ppb. There was no correlation between hepatic pathology and halitosis. Fifty-two percent of all subjects had poor oral hygiene, strongly correlated with high VSC values (P<0.05) whereas the remaining 48% with good hygiene had normal levels of VSC. Within the limitations of this study, high values of VSC were not associated with the presence of hepatic disease.

A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men.

PubMed

Zhang, G Y; Gu, Y Q; Wang, X H; Cui, Y G; Bremner, W J

1999-10-01

This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.

Effect of hepatitis B virus infection on sperm quality and oxidative stress state of the semen of infertile males.

PubMed

Qian, Li; Li, Qiong; Li, Haibo

2016-09-01

The effects of hepatitis B virus (HBV) infection on sperm quality and oxidative stress state of the semen of infertile males remain undetermined. Normal males and 60 semen samples from infertile males (with or without HBV infection) were subjected to semen analysis. Semen volume, semen pH, sperm density, percentage of forward, movement of sperm, sperm activation rate, sperm survival rate, rate of normal sperm morphology of infertile males with HBV infection were significantly lower than those of infertile males without genital infection and of normal males (P<.05), while interleukin (IL)-17, IL-18, and malondialdehyde (MDA) levels in subjects with HBV infection were significantly higher than those of infertile males without genital infection and of normal males (P<.05). In patients with HBV infection, MDA level was found to be negatively correlated with semen quality, but positively correlated with semen IL-17 and IL-18 concentrations. HBV infection increased MDA level, induced abnormal expression of IL-17 and IL-18, and negatively affected male reproductive capacity, resulting in male infertility. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Constant light affects retinal dopamine levels and blocks deprivation myopia but not lens-induced refractive errors in chickens.

PubMed

Bartmann, M; Schaeffel, F; Hagel, G; Zrenner, E

1994-01-01

Chickens were raised with either translucent occluders or lenses, both under normal light cycles (12-h light/12-h dark) and in constant light (CL). Under normal light cycles, eyes with occluders became very myopic, and eyes with lenses became either relatively hyperopic (positive lenses) or myopic (negative lenses). After the treatment, retinal dopamine (DA), DOPAC, and serotonin levels were measured by high-pressure liquid chromatography (HPLC-EC). A significant drop in daytime retinal DOPAC (-20%) was observed after 1 week of deprivation, and in both DOPAC (-40%) and DA (-30%) after 2 weeks of deprivation. No changes in retinal serotonin levels were found. Retinal DA or DOPAC content remained unchanged after 2 or 4 days of lens wearing even though the lenses had already exerted their maximal effect on axial eye growth. When the chickens were raised in CL, development of deprivation myopia was reduced (8 days CL) or entirely blocked (13 days CL). Lens-induced changes in eye growth were not different after either 6 or 11 days in CL, compared to animals raised in a normal light cycle. Thirteen days of CL resulted in a dramatic reduction of DA and DOPAC levels, but serotonin levels were also lowered. The results suggest that lens-induced changes in refraction may not be dependent on dopaminergic pathways whereas deprivation myopia requires normal diurnal DA rhythms to develop.

Serum creatinine and uric acid levels in pregnant urban African and Caucasian women.

PubMed

Nduka, N; Ekeke, G I

1986-12-01

Serum creatinine and uric acid concentrations were determined for 117 pregnant urban African women and 109 pregnant Caucasian women covering the three trimesters of pregnancy. The creatinine levels for Caucasians rose as pregnancy progressed, exceeding the normal adult level, while that for Africans rose only slightly and only during the last trimester of pregnancy. A similar observation was made for uric acid levels except that the rise in Africans commenced earlier than it did for creatinine, commencing from about the second trimester. Also, the levels in both groups of people remained within the normal adult range. The increased levels of these non-protein nitrogen compounds during pregnancy was attributable to increased metabolism associated with the condition. The difference observed between the Caucasians and Africans was attributed to the better protein nutritional status of the former. It is suggested that the creatinine "curve" especially for the Caucasians could be utilized in the monitoring of foetal well-being.

Persistence of Repair Proteins at Unrepaired DNA Damage Distinguishes Diseases with ERCC2 (XPD) Mutations: Cancer-Prone Xeroderma Pigmentosum vs. Non-Cancer-Prone Trichothiodystrophy

PubMed Central

Boyle, Jennifer; Ueda, Takahiro; Oh, Kyu-Seon; Imoto, Kyoko; Tamura, Deborah; Jagdeo, Jared; Khan, Sikandar G.; Nadem, Carine; DiGiovanna, John J.; Kraemer, Kenneth H.

2012-01-01

Patients with xeroderma pigmentosum (XP) have a 1,000-fold increase in ultraviolet (UV)-induced skin cancers while trichothiodystrophy (TTD) patients, despite mutations in the same genes, ERCC2 (XPD) or ERCC3 (XPB), are cancer-free. Unlike XP cells, TTD cells have a nearly normal rate of removal of UV-induced 6-4 photoproducts (6-4PP) in their DNA and low levels of the basal transcription factor, TFIIH. We examined seven XP, TTD, and XP/TTD complex patients and identified mutations in the XPD gene. We discovered large differences in nucleotide excision repair (NER) protein recruitment to sites of localized UV damage in TTD cells compared to XP or normal cells. XPC protein was rapidly localized in all cells. XPC was redistributed in TTD, and normal cells by 3 hr postirradiation, but remained localized in XP cells at 24-hr postirradiation. In XP cells recruitment of other NER proteins (XPB, XPD, XPG, XPA, and XPF) was also delayed and persisted at 24 hr (p < 0.001). In TTD cells with defects in the XPD, XPB, or GTF2H5 (TTDA) genes, in contrast, recruitment of these NER proteins was reduced compared to normals at early time points (p < 0.001) and remained low at 24 hr postirradiation. These data indicate that in XP persistence of NER proteins at sites of unrepaired DNA damage is associated with greatly increased skin cancer risk possibly by blockage of translesion DNA synthesis. In contrast, in TTD, low levels of unstable TFIIH proteins do not accumulate at sites of unrepaired photoproducts and may permit normal translesion DNA synthesis without increased skin cancer. PMID:18470933

Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin

PubMed Central

Rowe, Peter S.N.; Matsumoto, Naoko; Jo, Oak D.; Shih, Remi N.J.; Oconnor, Jeannine; Roudier, Martine P.; Bain, Steve; Liu, Shiguang; Harrison, Jody; Yanagawa, Norimoto

2012-01-01

Increased expression of several osteoblastic proteases and MEPE (a bone matrix protein) occurs in X-linked hypophosphatemic rickets (hyp). This is associated with an increased release of a protease-resistant MEPE peptide (ASARM peptide), a potent inhibitor of mineralization. Cathepsin B cleaves MEPE releasing ASARM peptide and hyp osteoblast/osteocyte cells hypersecrete cathepsin D, an activator of cathepsin B. Our aims were to determine whether cathepsin inhibitors correct the mineralization defect in vivo and whether hyp-bone ASARM peptide levels are reduced after protease treatment. Normal littermates and hyp mice (n = 6) were injected intraperitoneally once a day for 4 weeks with pepstatin, CAO74 or vehicle. Animals were then sacrificed and bones plus serum removed for comprehensive analysis. All hyp mice groups (treated and untreated) remained hypophosphatemic with serum 1,25 vitamin D3 inappropriately normal. Serum PTH was significantly elevated in all hyp mice groups relative to normal mice (P = 0.0017). Untreated hyp mice had six-fold elevated levels of serum alkaline-phosphatase and two-fold elevated levels of ASARM peptides relative to normal mice (P < 0.001). In contrast, serum alkaline phosphatase and serum ASARM peptides were significantly reduced (normalized) in hyp mice treated with CA074 or pepstatin. Serum FGF23 levels remained high in all hyp animal groups (P < 0.0001). Hyp mice treated with protease inhibitors showed dramatic reductions in unmineralized osteoid (femurs) compared to control hyp mice (Goldner staining). Also, hyp animals treated with protease inhibitors showed marked and significant improvements in growth plate width (42%), osteoid thickness (40%) and cortical area (40%) (P < 0.002). The mineralization apposition rate, bone formation rate and mineralization surface were normalized by protease-treatment. High-resolution pQCT mineral histomorphometry measurements and uCT also confirmed a marked mineralization improvement. Finally, the growth plate and cortical bone of hyp femurs contained a massive accumulation of osteoblast-derived ASARM peptide(s) that was reduced in hyp animals treated with CA074 or pepstatin. This study confirms in vivo administration of cathepsin inhibitors improves bone mineralization in hyp mice. This may be due to a protease inhibitor mediated decrease in proteolytic degradation of the extracellular matrix and a reduced release of ASARM peptides (potent mineralization inhibitors). PMID:16762607

Stress-induced ascorbic acid depletion and cortisol production in two salmonid fishes

USGS Publications Warehouse

Wedemeyer, Gary

1969-01-01

Interrenal ascorbic acid and serum cortisol were measured in non-specificity stressed yearling coho salmon and rainbow trout.Interrenal ascorbate was markedly decreased during stress but increased to normal if adaptation occurred.Serum cortisol was elevated by non-specific stress and remained high after interrenal ascorbate had returned to initial levels.

Ireland's Generic Repeat Design Schools Programme

ERIC Educational Resources Information Center

Sheppard, Tony

2011-01-01

The Irish Department of Education and Skills (DoE) is strongly committed to energy efficiency and to reducing CO[subscript 2] by developing and implementing energy level ceilings in relation to school design that aim to remain below half of the accepted good practice in the field. This approach works within normal departmental budgetary limits to…

The relationship of the p–k titre to the serum ige level in patients with leprosy

PubMed Central

Hamburger, R. N.; Fernandez-Cruz, E.; Arnaiz, A.; Perez, B.; Bootello, A.

1974-01-01

Fifty patients with leprosy were found to have P–K titres inversely related to their serum IgE levels. Patients with leprosy react in a manner similar to normal individuals and to patients with other diseases. Serum IgG, IgM, IgA and complement were measured in twenty-five of the leprosy patients in addition to the serum IgE and only the IgG significantly positively correlated with the serum IgE. All of these leprosy patients were shown to react to exogenous histamine and they released endogenous histamine when chemically stimulated. Two patients had absent flare responses with normal weals, the remaining forty-eight had complete weal and flare responses. Higher serum IgE levels were noted in those patients with recent institution of chemotherapy. PMID:4143279

Ontogeny of brain and blood serotonin levels in 5-HT receptor knockout mice: potential relevance to the neurobiology of autism.

PubMed

Janusonis, Skirmantas; Anderson, George M; Shifrovich, Ilya; Rakic, Pasko

2006-11-01

The most consistent neurochemical finding in autism has been elevated group mean levels of blood platelet 5-hydroxytryptamine (5-HT, serotonin). The origin and significance of this platelet hyperserotonemia remain poorly understood. The 5-HT(1A) receptor plays important roles in the developing brain and is also expressed in the gut, the main source of platelet 5-HT. Post-natal tissue levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan were examined in the brain, duodenum and blood of 5-HT(1A) receptor-knockout and wild-type mice. At 3 days after birth, the knockout mice had lower mean brain 5-HT levels and normal mean platelet 5-HT levels. Also, at 3 days after birth, the mean tryptophan levels in the brain, duodenum and blood of the knockout mice were around 30% lower than those of the wild-type mice. By 2 weeks after birth, the mean brain 5-HT levels of the knockout mice normalized, but their mean platelet 5-HT levels became 24% higher than normal. The possible causes of these dynamic shifts were explored by examining correlations between central and peripheral levels of 5-HT, 5-HIAA and tryptophan. The results are discussed in relation to the possible role of 5-HT in the ontogeny of autism.

Hematocrit Level could Reflect Inflammatory Response and Disease Activity in Patients with Systemic Lupus Erythematosus.

PubMed

Yang, Min; Ma, Ning; Fu, Haitao; Wei, Tingting; Tang, Qingqin; Qin, Baodong; Yang, Zaixing; Zhong, Renqian

2015-01-01

The previous study has reported the association of hematocrit (HCT) with inflammation in several diseases. But the role of HCT in systemic lupus erythematosus (SLE) remained unclear. We tried to evaluate the clinical significance of HCT levels in patients with SLE. A retrospective study including 127 adult SLE patients and 146 normal healthy controls was performed. HCT levels between SLE patients and normal healthy controls were compared, and correlations between HCT and clinical characteristics were evaluated. HCT levels in SLE patients were significantly decreased as compared with the normal healthy controls and negatively correlated with C-reactive protein (CRP) (r = -0.336, p < 0.01), erythrocyte sedimentation rate (ESR) (r = -0.332, p < 0.01), and SLEDAI scores (r = -0.376, p < 0.01). HCT levels were also significantly lower in SLE patients with decreased C3 and C4 as compared with those in SLE patients with normal C3 and C4, indicating that HCT was positively correlated with C3 and C4 levels (r = 0.272, p < 0.01; r = 0.273, p < 0.01). HCT was decreased in SLE patients with the presence of anti-Sm and anti-RNP antibodies as compared with those without these auto-antibodies (p = 0.013, p < 0.01). After adjusting RBC count and hemoglobin level, multiple linear regression analysis showed that HCT was independently associated with disease activity in SLE patients. In addition, HCT levels were elevated after treatment. HCT is correlated with CRP, ESR, and SLEDAI, suggesting that HCT could reflect inflammatory response and disease activity in SLE patients.

Excess body weight affects HbA1c progression irrespective of baseline HbA1c levels in Japanese individuals: a longitudinal retrospective study.

PubMed

Nakajima, Kei; Suwa, Kaname

2015-01-01

Obese individuals with normal HbA1c levels and low-body-weight individuals with high-normal HbA1c levels are frequently encountered in clinical settings, but the effects of these phenotypes on the onset of diabetes are poorly understood. Therefore, we addressed this issue in a longitudinal study. We analyzed clinical parameters, including body mass index (BMI) and HbA1c levels, in 5325 non-diabetic Japanese people aged 20-75 years who underwent four medical checkups between 1999 (baseline) and 2007. The subjects were then classified into six baseline BMI categories, each of which was divided into two HbA1c groups, resulting in a total of 12 groups. In 405 obese subjects with a normal baseline HbA1c (BMI ≥ 27.0 kg/m(2), HbA1c 5.2-5.6%), the mean HbA1c level increased during the study period, and 50.9% developed prediabetes/diabetes. In contrast, in 77 low-body-weight subjects with a high-normal baseline HbA1c (BMI ≤ 18.9 kg/m(2), HbA1c 5.7-6.4%), the mean HbA1c level remained constant. Similar changes occurred in the other groups during the study, resulting in a linear increase in HbA1c levels with increasing BMI. Our results suggest that approximately half of the obese individuals with HbA1c in the normal range develop prediabetes or diabetes within 8 years, whereas low-body-weight individuals with high-normal HbA1c are less likely to exhibit worsening in glycemia. Thus, excess body weight may be the primary therapeutic target to prevent the early onset of diabetes, regardless of the individual's HbA1c.

Partitioning the variability of fasting plasma glucose levels in pedigrees. Genetic and environmental factors.

PubMed

Boehnke, M; Moll, P P; Kottke, B A; Weidman, W H

1987-04-01

Fasting plasma glucose measurements made in 1972-1977 on normoglycemic individuals in three-generation Caucasian pedigrees from Rochester, Minnesota were analyzed. The authors determined the contributions of polygenic loci and environmental factors to fasting plasma glucose variability in these pedigrees. To that end, fasting plasma glucose measurements were normalized by an inverse normal scores transformation and then regressed separately for males and females on measured concomitants including age, body mass index (weight/height2), season of measurement, sex hormone use, and diuretic use. The authors found that 27.7% of the variability in normalized fasting plasma glucose in these pedigrees is explained by these measured concomitants. Subsequent variance components analysis suggested that unmeasured polygenic loci and unmeasured shared environmental factors together account for at least an additional 36.7% of the variability in normalized fasting plasma glucose, with genes alone accounting for at least 27.3%. These results are consistent with the known familiality of diabetes, for which fasting plasma glucose level is an important predictor. Further, these familial factors provide an explanation for at least half the variability in normalized fasting plasma glucose which remains after regression on known concomitants.

Unreliability of classic provocative tests for the diagnosis of growth hormone deficiency.

PubMed

Mazzola, A; Meazza, C; Travaglino, P; Pagani, S; Frattini, D; Bozzola, E; Corneli, G; Aimaretti, G; Bozzola, M

2008-02-01

In this study we investigated 9 prepubertal children with blunted GH response to classic pharmacological stimuli in contrast with normal auxological evaluation. The children were followed to evaluate their growth velocity for a longer period before starting replacement GH therapy. To evaluate the pituitary reserve a supraphysiologic stimulus such as GHRH plus arginine was used. Serum GH levels were measured by a time-resolved immunofluorimetric assay before and after 1 microg/kg body weight iv injection of GHRH, while serum PRL, IGF-I, and insulin were evaluated only in basal conditions using an automatic immunometric assay. Out of 9 studied subjects, 7 underwent GHRH plus arginine administration and showed a normal GH response; the parents of the remaining 2 children refused the test. Normal serum levels of PRL, IGF-I, insulin, and a normal insulin sensitivity were observed in all children. After 1 yr, the growth rate in each patient was further improved and reached almost normal values. Our results further confirm that the decision to start replacement GH therapy should be based on both auxological parameters and laboratory findings. The GHRH plus arginine test appears to be useful to identify false GH deficiency in children showing a blunted GH response to classic stimuli in contrast with normal growth rate.

Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation.

PubMed

Lundgren, Jakob; Sandqvist, Anna; Hedeland, Mikael; Bondesson, Ulf; Wikström, Gerhard; Rådegran, Göran

2018-04-12

Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered "normal" after HT.

Quantitation of normal CFTR mRNA in CF patients with splice-site mutations

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

Zhou, Z.; Olsen, J.C.; Silverman, L.M.

Previously we identified two mutations in introns of the CFTR gene associated with partially active splice sites and unusual clinical phenotypes. One mutation in intron 19 (3849+10 kb C to T) is common in CF patients with normal sweat chloride values; an 84 bp sequence from intron 19, which contains a stop codon, is inserted between exon 19 and exon 20 in most nasal CFTR transcripts. The other mutation in intron 14B (2789+5 G to A) is associated with elevated sweat chloride levels, but mild pulmonary disease; exon 14B (38 bp) is spliced out of most nasal CFTR transcipts. Themore » remaining CFTR cDNA sequences, other than the 84 bp insertion of exon 14B deletion, are identical to the published sequence. To correlate genotype and phenotype, we used quantitative RT-PCR to determine the levels of normally-spliced CFTR mRNA in nasal epithelia from these patients. CFTR cDNA was amplified (25 cycles) by using primers specific for normally-spliced species, {gamma}-actin cDNA was amplified as a standard.« less

[A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

PubMed

Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

2005-12-01

A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

[Effect of a tissue oxygenator (almitrine + raubasine) on the metabolism of 2,3-diphosphoglycerate of rabbits submitted by hypoxia].

PubMed

Callis, A; Dorance, M; Magnan de Bornier, B

1980-01-01

In normoxic rabbits, the intravenous injection (1 mg/kg) of the product (almitrine + raubasine) do not modify the erythrocytic level of 2,3-DPG. But, after hypoxia (the rabbits being submitted to an oxygen pressure of 7,8 kPa during 20 minutes) the same dose of this product induce a durable rise of erythrocytic 2,3-DPG level which remain, 24 hours latter, + 15% above normal.

Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

PubMed

Holcombe, H; Parry, N M; Rick, M; Brown, D E; Albers, T M; Refsal, K R; Morris, J; Kelly, R; Marko, S T

2015-07-01

A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs. © The Author(s) 2014.

Elevated serum levels of TPS and CYFRA 21-1 predict poor prognosis in advanced non-small-cell lung cancer patients treated with gefitinib.

PubMed

Chen, Fengsheng; Luo, Xi; Zhang, Jinbiao; Lu, Yang; Luo, Rongcheng

2010-09-01

Serum concentrations of tissue polypeptide-specific antigen (TPS) and Cytokeratin-19-Fragments (CYFRA 21-1) before operation or chemotherapy have been proved to be a useful prognostic tool for patients with NSCLC, but the related data for advanced NSCLC patients treated with gefitinib are limited. We retrospectively reviewed 122 advanced NSCLC patients treated with gefitinib between April 2002 and August 2007. Multiple clinical factors including pretreatment serum levels of TPS and CYFRA 21-1, age, gender, performance status (PS), smoking history, stage, histology, the number of prior chemotherapy and the patients' clinical outcomes were analyzed. Patients without elevated serum TPS levels had a more RR (36.8%) than those with elevated serum TPS levels (18.5%) (P = 0.023), nevertheless, a similar result was not seen in patients with normal CYFRA 21-1 levels. For patients with normal vs. high TPS levels, the median survival times (MSTs) were 15.9 vs. 7.3 months (P = 0.001). For patients with normal vs. high CYFRA 21-1, the MSTs were 15.4 vs. 7.5 months (P = 0.003). Moreover, for patients with both elevated, vs. one elevated and both normal TPS and CYFRA 21-1 levels, the MSTs were 5.4 vs. 11.4 months (P = 0.001), and 16.5 months (P < 0.001), respectively. In multivariate analysis, TPS (P = 0.001) and CYFRA 21-1 (P = 0.005) alone or combination (P < 0.001) remained significant correlation to survival. In NSCLC patients with gefitinib therapy, pretreatment serum levels of TPS and CYFRA 21-1 alone or combined might be independent prognostic factors, and the pretreatment serum TPS level may predict the tumor response.

Comparison of waxy and normal potato starch remaining granules after chemical surface gelatinization: pasting behavior and surface morphology.

PubMed

Huang, Junrong; Chen, Zhenghong; Xu, Yalun; Li, Hongliang; Liu, Shuxing; Yang, Daqing; Schols, Henk A

2014-02-15

To understand the contribution of granule inner portion to the pasting property of starch, waxy potato starch and two normal potato starches and their acetylated starch samples were subjected to chemical surface gelatinization by 3.8 mol/L CaCl2 to obtain remaining granules. Native and acetylated, original and remaining granules of waxy potato starch had similar rapid visco analyzer (RVA) pasting profiles, while those of two normal potato starches behaved obviously different from each other. All remaining granules had lower peak viscosity than the corresponding original granules. Contribution of waxy potato starch granule's inner portion to the peak viscosity was significant more than those of normal potato starches. The shell structure appearing on the remaining granule surface for waxy potato starch was smoother and thinner than that for normal potato starches as observed by scanning electron microscopy, indicating a more regular structure of shell and a more ordered packing of shell for waxy potato starch granules. The blocklet size of waxy potato starch was smaller and more uniform than those of normal potato starches as shown by atomic force microscopy images of original and remaining granules. In general, our results provided the evidence for the spatial structure diversity between waxy and normal potato starch granules: outer layer and inner portion of waxy potato starch granule had similar structure, while outer layer had notably different structure from inner portion for normal potato starch granule. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of heat-moisture treatment reaction conditions on the physicochemical and structural properties of maize starch: moisture and length of heating.

PubMed

Sui, Zhongquan; Yao, Tianming; Zhao, Yue; Ye, Xiaoting; Kong, Xiangli; Ai, Lianzhong

2015-04-15

Changes in the properties of normal maize starch (NMS) and waxy maize starch (WMS) after heat-moisture treatment (HMT) under various reaction conditions were investigated. NMS and WMS were adjusted to moisture levels of 20%, 25% and 30% and heated at 100 °C for 2, 4, 8 and 16 h. The results showed that moisture content was the most important factor in determining pasting properties for NMS, whereas the heating length was more important for WMS. Swelling power decreased in NMS but increased in WMS, and while the solubility index decreased for both samples, the changes were largely determined by moisture content. The gelatinisation temperatures of both samples increased with increasing moisture content but remained unchanged with increasing heating length. The Fourier transform infrared (FT-IR) absorbance ratio was affected to different extents by the moisture levels but remained constant with increasing the heating length. The X-ray intensities increased but relative crystallinity decreased to a greater extent with increasing moisture content. This study showed that the levels of moisture content and length of heating had significant impacts on the structural and physicochemical properties of normal and waxy maize starches but to different extents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamics of Cytokine-like Activity in the Hyperplasic Ovary of Ex-fissiparous Planarians.

PubMed

Harrath, Abdel Halim; Semlali, Abdelhabib; Mansour, Lamjed; Aldahmash, Waleed; Omar, Suliman Y Al; Anazi, Mohamed S Al; Nyengaard, Jens R; Alwasel, Saleh

2017-02-01

The origin of infertility in the hyperplasic ovary of ex-fissiparous planarians remains poorly understood. In a previous study we demonstrated that a complex process of early autophagy, followed by apoptotic processes, occurs in the hyperplasic ovary of the freshwater planarian Dugesia arabica. The present study aimed to investigate whether the mRNA expression levels of selected mRNA-like genes are altered in the hyperplasic ovary of the ex-fissiparous freshwater planarian D. arabica compared to the normal ovary. Using human cytokine-specific primers including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), we have successfully amplified by real-time polymerase chain reaction some transcripts that could be similar to those amplified in human. The transcript levels of the human-like transcript (IL-1-like and TNF-α-like) were significantly higher, 4.89- and 3.41-fold, respectively, in the hyperplasic ovary compared to the normal ovary (P < 0.05). However, although IL-6-like levels were higher in the hyperplasic ovary than the normal ovary (2.57-fold), this difference was not significant (P > 0.05). Immunohistochemical labeling supported the quantitative real-time PCR, showing that, like their respective mRNA expression levels, IL-1, IL-6, and TNF-α-like proteins are more highly expressed in the hyperplasic ovary than in the normal ovary.

Spin-transfer torque magnetoresistive random-access memory technologies for normally off computing (invited)

NASA Astrophysics Data System (ADS)

Ando, K.; Fujita, S.; Ito, J.; Yuasa, S.; Suzuki, Y.; Nakatani, Y.; Miyazaki, T.; Yoda, H.

2014-05-01

Most parts of present computer systems are made of volatile devices, and the power to supply them to avoid information loss causes huge energy losses. We can eliminate this meaningless energy loss by utilizing the non-volatile function of advanced spin-transfer torque magnetoresistive random-access memory (STT-MRAM) technology and create a new type of computer, i.e., normally off computers. Critical tasks to achieve normally off computers are implementations of STT-MRAM technologies in the main memory and low-level cache memories. STT-MRAM technology for applications to the main memory has been successfully developed by using perpendicular STT-MRAMs, and faster STT-MRAM technologies for applications to the cache memory are now being developed. The present status of STT-MRAMs and challenges that remain for normally off computers are discussed.

Blood Levels of Trace Elements in Children with Attention-Deficit Hyperactivity Disorder: Results from a Case-Control Study.

PubMed

Yang, Rongwang; Zhang, Yanyi; Gao, Weijia; Lin, Nannan; Li, Rong; Zhao, Zhengyan

2018-06-16

Some trace elements may participate in the pathogenesis of attention-deficit hyperactivity disorder (ADHD). This study aimed to investigate the trace element status of zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg), and lead (Pb) in children with ADHD, and to compare them with normal controls. Associations between examined elements and SNAP-IV rating scores of ADHD symptoms were also assessed. Four hundred nineteen children with ADHD (8.8 ± 2.1 years) and 395 matched normal controls (8.9 ± 1.7 years) were recruited in the study. The concentrations of Zn, Fe, Cu, Mg, and Pb in the whole blood were measured by atomic absorption spectrometry. Lower zinc levels (P < 0.001) and the number out of normal ranges (P = 0.015) were found in children with ADHD when compared with the normal control group. The difference remained when adjusting the factor of BMI z-score. No significant between-group differences were found in levels of other elements. Zinc levels were negatively correlated with parent-rated scores of inattentive subscale of SNAP-IV (r = - 0.40) as well as with total score of SNAP-IV (r = - 0.24). Other significant associations were not observed. The present results indicated that there were alterations in blood levels of zinc, which was associated with the symptom scores of ADHD.

Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation

PubMed Central

Liao, Zhenhua; Fogel, Guy R.; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

2015-01-01

Background The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Material/Methods Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Results Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). Conclusions ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion. PMID:26529430

Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation.

PubMed

Liao, Zhenhua; Fogel, Guy R; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

2015-11-03

The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion.

Successful resection of a giant mediastinal non-seminomatous germ cell tumor showing fluorodeoxyglucose accumulation after neoadjuvant chemotherapy: report of a case.

PubMed

Takada, Kazuki; Morodomi, Yosuke; Okamoto, Tatsuro; Suzuki, Yuzo; Fujishita, Takatoshi; Kitahara, Hirokazu; Shimamatsu, Shinichiro; Kohno, Mikihiro; Kawano, Daigo; Hidaka, Noriko; Nakanishi, Yoichi; Maehara, Yoshihiko

2014-05-01

A 32-year-old man presented with a mediastinal non-seminomatous germ cell tumor showing fluorodeoxyglucose (FDG) accumulation (maximum standardized uptake value = 22.21) and extremely elevated blood alpha-fetoprotein (AFP) level (9203.0 ng/ml). The patient underwent 4 cycles of neoadjuvant chemotherapy (cisplatin, bleomycin, and etoposide), which normalized the AFP level and reduced the tumor size, allowing complete resection without a support of extracorporeal circulation. Despite preoperative positron emission tomography revealing increased FDG uptake in the residual tumor (maximum standardized uptake value = 3.59), the pathologic evaluation revealed that no viable germ cell tumor cells remained. We believe FDG uptake should not be used as a criterion for surgical resection after neoadjuvant chemotherapy. It is appropriate to resect the residual tumor regardless of FDG uptake after induction chemotherapy if a tumor is resectable and the AFP level normalizes.

Ectopic hyperprolactinaemia in a woman with a mesocolic perivascular epithelioid cell tumor ("PEComa").

PubMed

Proust-Lemoine, E; Mitchell, V; Deruelle, P; Lamblin, A; Néraud, B; Leroy, X; Leteurtre, E; Dewailly, D

2008-06-01

Ectopic prolactin secretion remains exceptional and originates mainly from malignant tumors. We report the case of a 47-year-old woman who presented amenorrhea leading to unravel important hyperprolactinaemia (269 ng/mL) with no hypothalamo-pituitary mass on magnetic resonance imaging (MRI). Pelvic imaging revealed the presence of a large pelvic mass that originated from the mesocolon. After complete surgical extraction, histological examination was in favour of a "perivascular epithelioid cell tumor" (PEComa). Prolactin levels normalized after surgical extraction and remained normal after a 3-year follow-up, totally free of tumour recurrence and/or metastasis. This suggests that hyperprolactinaemia was most likely related to the PEComa, despite negative reactions with antiprolactin antibodies at immunohistochemistry. Alternatively to a direct prolactin secretion by the tumor, one could hypothesize that the tumour secreted a prolactin stimulating factor or a dopamine antagonist that could not be identified. In conclusion, in face of an important hyperprolactinaemia without any hypothalamic-pituitary mass, it remains important to search for an ectopic prolactin production, such as a PEComa.

Ectopic Cushing's syndrome secondary to olfactory neuroblastoma.

PubMed

Yu, Kenny; Roncaroli, Federico; Kearney, Tara; Ewins, David; Beeharry, Deepa; Naylor, Thomas; Ray, David; Bhalla, Rajiv; Gnanalingham, Kanna

2018-05-01

We present the case of a patient with Cushing's syndrome secondary to ectopic ACTH secretion. A MR of the head showed a left-sided nasal mass extending down from the cribriform plate. The patient underwent endoscopic resection with nearly complete removal of the mass. Histological examination showed an ACTH-secreting olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal range after surgery and have remained normal for over a year. ONB is a rare cause for ectopic ACTH secretion. This case highlights the diagnostic and management difficulties in patients with ectopic ACTH secretion, and provides a brief review of ONB.

Stability of Early EEG Background Patterns After Pediatric Cardiac Arrest.

PubMed

Abend, Nicholas S; Xiao, Rui; Kessler, Sudha Kilaru; Topjian, Alexis A

2018-05-01

We aimed to determine whether EEG background characteristics remain stable across discrete time periods during the acute period after resuscitation from pediatric cardiac arrest. Children resuscitated from cardiac arrest underwent continuous conventional EEG monitoring. The EEG was scored in 12-hour epochs for up to 72 hours after return of circulation by an electroencephalographer using a Background Category with 4 levels (normal, slow-disorganized, discontinuous/burst-suppression, or attenuated-featureless) or 2 levels (normal/slow-disorganized or discontinuous/burst-suppression/attenuated-featureless). Survival analyses and mixed-effects ordinal logistic regression models evaluated whether the EEG remained stable across epochs. EEG monitoring was performed in 89 consecutive children. When EEG was assessed as the 4-level Background Category, 30% of subjects changed category over time. Based on initial Background Category, one quarter of the subjects changed EEG category by 24 hours if the initial EEG was attenuated-featureless, by 36 hours if the initial EEG was discontinuous or burst-suppression, by 48 hours if the initial EEG was slow-disorganized, and never if the initial EEG was normal. However, regression modeling for the 4-level Background Category indicated that the EEG did not change over time (odds ratio = 1.06, 95% confidence interval = 0.96-1.17, P = 0.26). Similarly, when EEG was assessed as the 2-level Background Category, 8% of subjects changed EEG category over time. However, regression modeling for the 2-level category indicated that the EEG did not change over time (odds ratio = 1.02, 95% confidence interval = 0.91-1.13, P = 0.75). The EEG Background Category changes over time whether analyzed as 4 levels (30% of subjects) or 2 levels (8% of subjects), although regression analyses indicated that no significant changes occurred over time for the full cohort. These data indicate that the Background Category is often stable during the acute 72 hours after pediatric cardiac arrest and thus may be a useful EEG assessment metric in future studies, but that some subjects do have EEG changes over time and therefore serial EEG assessments may be informative.

Assessment of tenascin-C levels in ventricular noncompaction/hypertrabeculation patients: a cross-sectional study.

PubMed

Erer, Hatice Betul; Guvenc, Tolga Sinan; Kemik, Ahu Sarbay; Yilmaz, Hale; Kul, Seref; Altay, Servet; Oz, Dilaver; Zeren, Gonul; Ekmekci, Ahmet; Zencirci, Aycan Esen; Sayar, Nurten; Eren, Mehmet

2014-02-01

Ventricular noncompaction/hypertrabeculation (NC/HT) is a rare form of congenital cardiomyopathy. We aimed to investigate the presence of serum tenascin-C (TN-C) in adult patients with NC/HT and evaluate its value. Serum TN-C levels were measured by ELISA in 50 NC/HT patients both with/without systolic dysfunction and in 23 normal controls. Systolic dysfunction was defined as ejection fraction (EF) ≤ 40. Mann-Whitney U-test and ROC curve analysis were done. Of 49 NC/HT patients, 24 (49%) patients had systolic dysfunction (mean age 36 ± 15) and 25 patients (51%) had normal systolic function (mean age 36 ± 17). The ages between groups were not different. The mean levels of serum TN-C in patients with or without systolic dysfunction were 26 ± 10 ng/mL and 26 ± 8 ng/mL respectively, compared to normal controls, 7 ± 2 ng/mL (P < 0.001). No significance was observed between 2 groups of NC/HT patients regarding TN-C levels (P = 0.8). The ROC curve analysis revealed that a TN-C value of 11.7 ng/mL identified patients with NC/HT with 100% sensitivity and specifity. High serum TN-C levels are present in adult NC/HT cardiomyopathy even when left ventricular systolic function remains normal. Also, serum TN-C levels could be regarded as a candidate biomarker in the diagnosis of NC/HT which needs to be tested in larger prospective studies. © 2013, Wiley Periodicals, Inc.

ESTROGEN LEVELS DO NOT RISE WITH TESTOSTERONE TREATMENT FOR TRANSGENDER MEN.

PubMed

Chan, Kelly J; Jolly, Divya; Liang, Jennifer J; Weinand, Jamie D; Safer, Joshua D

2018-04-01

Existing transgender treatment guidelines suggest that for transmasculine treatment, there is a possible need for estrogen-lowering strategies adjunct to testosterone therapy. Further, guidelines advocate consideration of prophylactic female reproductive tissue surgeries for transgender men to avoid the possibility of estrogen-related health risks. Despite the paucity of objective data, some transgender men seek conversion inhibitors. We sought to determine estradiol levels in transgender men treated with testosterone therapy and the change in those levels with treatment, if any. Estradiol levels were extracted from the electronic medical records of 34 anonymized transgender men treated with testosterone therapy at the Endocrinology Clinic at Boston Medical Center. Data were sufficient to observe 6 years of follow-up. With increased testosterone levels in trans-gender men, a significant decrease in estradiol levels was noted. There was a significant negative correlation between testosterone levels and body mass index, which may serve to explain part of the mechanism for the fall in estradiol levels. Even though the fall in estradiol levels was significant statistically, the actual levels remained within the normal male range, even with 6 years of follow-up. These data suggest that when exogenous testosterone is used to achieve normal serum male testosterone levels for transgender men, it is converted to normal male levels of estradiol, with some decline in those estradiol levels that might be attributable to a fall in fat mass. There appears to be no role for aromatase conversion inhibitors or other estrogen-reducing strategies in trans-gender men. Abbreviation: BMI = body mass index.

Molecular Signatures and Diagnostic Biomarkers of Cumulative Blast-Graded Mild TBI

DTIC Science & Technology

2014-12-01

100 ± 9% 191 ± 20%* Values are mean ± SE of 4 rats/ group expressed as percentage of control . The level of the averaged control for each...protein is arbitrarily set to 100 with SE adjusted proportionally with remaining groups normalized to the level in control . *Significantly increased...not significant vs sham; **- pɘ.05, and ***-pɘ.01 Rat number in each group ranged 4-7. Mean, pg/ml for GFAP and UCHL1 and AU in % control

Metabolic clearance and blood production rates of estradiol in hyperthyroidism.

PubMed

Ridgway, E C; Longcope, C; Maloof, F

1975-09-01

The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.

Co-ingestion of methanol and nitromethane: using falsely elevated creatinine as indicator for methanol antidote use.

PubMed

Leonard, Charlene P; Akhtar, Javed

2007-07-01

To report a case of co-ingestion of methanol and nitromethane in a child in order to heighten the awareness of false elevation of serum creatinine from nitromethane ingestion. Case report. Pediatric intensive care unit. A 4-yr-old previously healthy girl ingested an unknown quantity of "Blue Thunder" model-engine fuel, which consisted of methanol and nitromethane. The patient was treated with fomepizole for methanol ingestion using elevated creatinine level as a reason for treatment. The patient was asymptomatic but her creatinine level increased ten-fold (from 0.4 mg/dL to 4 mg/dL) within 6 hrs. Blood urea nitrogen, anion gap, and osmolar gap remained within normal limits. When the serum creatinine level was measured with enzymatic method instead of Jaffe's method, a normal creatinine level was obtained. The falsely elevated creatinine level was due to nitromethane. The falsely elevated serum creatinine levels due to nitromethane ingestion can lead to unnecessary therapeutic interventions. We intend to heighten awareness of this potential misstep by reporting this case.

TOPEX/El Nino Watch - Warm Water Pool is Thinning, Feb, 5, 1998

NASA Technical Reports Server (NTRS)

1998-01-01

This image of the Pacific Ocean was produced using sea surface height measurements taken by the U.S.-French TOPEX/Poseidon satellite. The image shows sea surface height relative to normal ocean conditions on Feb. 5, 1998 and sea surface height is an indicator of the heat content of the ocean. The area and volume of the El Nino warm water pool that is affecting global weather patterns remains extremely large, but the pool has thinned along the equator and near the coast of South America. This 'thinning' means that the warm water is not as deep as it was a few months ago. Oceanographers indicate this is a classic pattern, typical of a mature El Nino condition that they would expect to see during the ocean's gradual transition back to normal sea level. In this image, the white and red areas indicate unusual patterns of heat storage; in the white areas, the sea surface is between 14 and 32 centimeters (6 to 13 inches) above normal; in the red areas, it's about 10 centimeters (4 inches) above normal. The green areas indicate normal conditions, while purple (the western Pacific) means at least 18 centimeters (7 inches) below normal sea level. The El Nino phenomenon is thought to be triggered when the steady westward blowing trade winds weaken and even reverse direction. This change in the winds allows a large mass of warm water (the red and white area) that is normally located near Australia to move eastward along the equator until it reaches the coast of South America. The displacement of so much warm water affects evaporation, where rain clouds form and, consequently, alters the typical atmospheric jet stream patterns around the world. Using satellite imagery, buoy and ship data, and a forecasting model of the ocean-atmosphere system, the National Oceanic and Atmospheric Administration, (NOAA), has continued to issue an advisory indicating the so-called El Nino weather conditions that have impacted much of the United States and the world are expected to remain through the spring.

For more information, please visit the TOPEX/Poseidon project web page at http://topex-www.jpl.nasa.gov

Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs.

PubMed

Rezk, Peter E; Graham, Jacob R; Moran, Theodore S; Gordon, Richard K; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2007-03-01

Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels.

[Clinical characteristics and analysis of mass spectrometric data in 33 patients with maple syrup urine disease].

PubMed

Yang, Nan; Han, Lian-shu; Ye, Jun; Qiu, Wen-juan; Zhang, Hui-wen; Gao, Xiao-lan; Wang, Yu; Li, Xiao-yan; Xu, Hao; Gu, Xue-fan

2012-10-30

To explore the clinical characteristics and the diagnostic method of maple syrup urine disease (MSUD). From January 2003 to December 2011, a total of 14 000 patients with suspected inherited metabolism diseases were tested. The blood levels of leucine and valine of these patients were detected by tandem mass spectrometry. The urinary level of branched-chain α-ketoacids was tested by gas chromatography-mass spectrometry. And the diagnosis was based on the elevated levels of leucine and valine in blood and branched-chain α-ketoacids in urine. Thirty-three MSUD patients were confirmed. Their median age of initial visit was 0.17 years old (range: 7 days to 30 years old). The peak onset age of them was 2-30 days old, including 28 cases of neonatal onset (84.8%). The presenting symptoms of 28 cases were feeding difficulties (n=14), poor response, lethargy and seizures. Their median blood levels of leucine and valine (1901 (458-5804) and 600 (315-1617) µmol/L) were significantly higher than their normal levels ((50-300) and (60-250) µmol/L, both P<0.01). Their urinary levels of 2-OH-isovaleric acid, 2-keto-isovaleric acid, 2-keto-3-methylvaleric acid, 2-keto-isocaproic and acetylglycine (262.5 (5.4-624.3), 35.8 (1.9-156.0), 133.8 (7.4-611.5), 518.7 (17.2-2121.2) and 280.5 (11.0-1087.9) respectively) significantly higher than their normal levels (0, <0.1, 0, 0, <0.1 respectively, all P<0.01). In 5 intermittent MSUD patients, their blood levels of leucine and valine (402 (348-958) and 556 (322-808) µmol/L) were significantly higher than their normal levels (both P<0.01). The urinary level of 2-OH-isovaleric acid was significantly higher than its normal levels (P<0.01) while the urinary levels of other α-ketoacids were normal. The confirmation of MSUD remains difficult because of a lack of specific clinical features. The detections of tandem mass spectrometry and gas chromatography-mass spectrometry may aid its early diagnosis.

Glycerol phenylbutyrate treatment in children with urea cycle disorders: pooled analysis of short and long-term ammonia control and outcomes.

PubMed

Berry, Susan A; Lichter-Konecki, Uta; Diaz, George A; McCandless, Shawn E; Rhead, William; Smith, Wendy; Lemons, Cynthia; Nagamani, Sandesh C S; Coakley, Dion F; Mokhtarani, Masoud; Scharschmidt, Bruce F; Lee, Brendan

2014-05-01

To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). UCD patients (n=26) ages 2months through 17years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammonia exposure (AUC0-24) and glutamine levels during equivalent steady-state dosing of GPB and sodium phenylbutyrate (NaPBA). These 26 patients plus an additional 23 patients also received GPB in one of three 12-month, open label extension studies, which assessed long-term ammonia control, hyperammonemic (HA) crises, amino acid levels, and patient growth. Mean ammonia exposure on GPB was non-inferior to NaPBA in each of the individual crossover studies. In the pooled analyses, it was significantly lower on GPB vs. NaPBA (mean [SD] AUC0-24: 627 [302] vs. 872 [516] μmol/L; p=0.008) with significantly fewer abnormal values (15% on GPB vs. 35% on NaPBA; p=0.02). Mean ammonia levels remained within the normal range during 12months of GPB dosing and, when compared with the 12months preceding enrollment, a smaller percentage of patients (24.5% vs. 42.9%) experienced fewer (17 vs. 38) HA crises. Glutamine levels tended to be lower with GPB than with NaPBA during short-term dosing (mean [SD]: 660.8 [164.4] vs. 710.0 [158.7] μmol/L; p=0.114) and mean glutamine and branched chain amino acid levels, as well as other essential amino acids, remained within the normal range during 12months of GPB dosing. Mean height and weight Z-scores were within normal range at baseline and did not change significantly during 12months of GPB treatment. Dosing with GPB was associated with 24-hour ammonia exposure that was non-inferior to that during dosing with NaPBA in individual studies and significantly lower in the pooled analysis. Long-term GPB dosing was associated with normal levels of glutamine and essential amino acids, including branched chain amino acids, age-appropriate growth and fewer HA crises as compared with the 12month period preceding enrollment. Copyright © 2014 Elsevier Inc. All rights reserved.

Glycerol Phenylbutyrate Treatment in Children with Urea Cycle Disorders: Pooled Analysis of Short and Long-term Ammonia Control and Outcomes

PubMed Central

Berry, Susan A.; Lichter-Konecki, Uta; Diaz, George A.; McCandless, Shawn E.; Rhead, William; Smith, Wendy; LeMons, Cynthia; Nagamani, Sandesh C.S.; Coakley, Dion F.; Mokhtarani, Masoud; Scharschmidt, Bruce F.; Lee, Brendan

2015-01-01

Objective To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). Study Design UCD patients (n=26) ages 2 months through 17 years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammonia exposure (AUC0–24) and glutamine levels during equivalent steady-state dosing of GPB and sodium phenylbutyrate (NaPBA). These 26 patients plus an additional 23 patients also received GPB in one of three 12-month, open label extension studies, which assessed long-term ammonia control, hyperammonemic (HA) crises, amino acids levels, and patient growth. Results Mean ammonia exposure on GPB was non-inferior to NaPBA in each of the individual crossover studies. In the pooled analyses, it was significantly lower on GPB vs. NaPBA (mean [SD] AUC0–24: 627 [302] vs. 872 [516] µmol/L; p=0.008) with significantly fewer abnormal values (15% on GPB vs. 35% on NaPBA; p = 0.02). Mean ammonia levels remained within the normal range during 12 months of GPB dosing and, when compared with the 12 months preceding enrollment, a smaller percentage of patients (24.5% vs. 42.9%) experienced fewer (17 vs. 38) HA crises. Glutamine levels tended to be lower with GPB than with NaPBA during short-term dosing (mean [SD]: 660.8 [164.4] vs. 710.0 [158.7] µmol/L; p=0.114) and mean glutamine and branched chain amino acids levels, as well as other essential amino acids, remained within the normal range during 12 months of GPB dosing. Mean height and weight Z-scores were within normal range at baseline and did not change significantly during 12 months of GPB treatment. Conclusions Dosing with GPB was associated with 24-hour ammonia exposure that was non-inferior to that during dosing with NaPBA in individual studies and significantly lower in the pooled analysis. Long-term GPB dosing was associated with normal levels of glutamine and essential amino acids, including branched chain amino acids, age-appropriate growth and fewer HA crises as compared with the 12 month period preceding enrollment. PMID:24630270

"Micromegaly": an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era.

PubMed

Butz, Laura B; Sullivan, Stephen E; Chandler, William F; Barkan, Ariel L

2016-12-01

Approximately 25 % of cases of clinically active acromegaly cases treated in our academic center between 1996 and 2000, were diagnosed in patients who had elevated plasma IGF-1 levels, but apparently "normal" 24-h mean plasma GH levels. The current study served to update the data for patients with acromegaly referred to our facility, after increasing awareness of this "normal" GH subpopulation throughout the medical community. A retrospective chart review was conducted on 157 patients with acromegaly who underwent resection of a confirmed somatotroph pituitary adenoma at the University of Michigan Health System between the dates of 1 Jan 2001 to 23 Sept 2015. Overall prevalence of acromegalic patients with "normal" GH levels, defined as GH <4.7 ng/mL, was 31 %. Over time, the percentage of patients with "normal" GH at diagnosis did not decline: 26 % from 2001 to 2005, 19 % from 2006 to 2010, and 47 % from 2011 to 2015. Mean pituitary tumor size was 1.8 ± 0.1 cm for the group with elevated GH, and 1.2 ± 0.1 cm for the group with "normal" GH (p < 0.001). Percent microadenomas was higher in a group with "normal" GH as compared to those with elevated GH (48 vs. 12 %, p < 0.001), and tumors >2 cm in the maximal diameter were encountered more frequently in the group with elevated GH (43 vs. 14 %, p < 0.001). Our data show that a substantial percentage of patients with clinical acromegaly have "normal" GH, and therefore strengthens the growing body of evidence which supports the leading role of IGF-1 levels in diagnostic evaluation. At the present time, questions about the natural course of "micromegaly" and treatment benefits compared to the subpopulation with elevated GH levels remain unanswered, but research continues to build on our understanding of the heterogeneous population of individuals.

Spectroscopic Axonal Damage of the Right Locus Coeruleus Relates to Selective Attention Impairment in Early Stage Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Gadea, Marien; Martinez-Bisbal, M. Carmen; Marti-Bonmati, Luis; Espert, Raul; Casanova, Bonaventura; Coret, Francisco; Celda, Bernardo

2004-01-01

Lower levels of N-acetylaspartate (NAA), a marker of axonal damage, have been found in the normal-appearing white matter (NAWM) of relapsing-remitting multiple sclerosis (RRMS) patients with low physical disability. However, its relation to the clinical status of these patients remains unclear. We explored the association between NAA levels…

Using Virtual Servers to Teach the Implementation of Enterprise-Level DBMSs: A Teaching Note

ERIC Educational Resources Information Center

Wagner, William P.; Pant, Vik

2010-01-01

One of the areas where demand has remained strong for MIS students is in the area of database management. Since the early days, this topic has been a mainstay in the MIS curriculum. Students of database management today typically learn about relational databases, SQL, normalization, and how to design and implement various kinds of database…

A 12-month phase 3 study of pasireotide in Cushing's disease.

PubMed

Colao, Annamaria; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Schoenherr, Ulrike; Mills, David; Salgado, Luiz Roberto; Biller, Beverly M K

2012-03-08

Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg (82 patients) or 900 μg (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 μg twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients. The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

High normal fasting blood glucose is associated with dementia in Chinese elders

PubMed Central

Mortimer, J.A.; Borenstein, A.R.; Ding, D.; DeCarli, C.; Zhao, Q.; Copenhaver, C.; Guo, Q.; Chu, S.; Galasko, D.; Salmon, D.P.; Dai, Q.; Wu, Y.; Petersen, R.; Hong, Z.

2010-01-01

Background Diabetes is a risk factor for MCI and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. Methods Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. Results Controlling for age, sex, education, body mass index, Hachinski Ischemic Score, MRI stroke, and normalized brain, hippocampal and white matter hyperintensity MRI volumes; higher FBG was associated with dementia vs. aMCI status (OR= 3.13; 95% CI:1.28–7.69). This association remained (OR= 7.75; 95% CI:1.10–55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, sex and education a significant association with FBG also was seen (OR=1.83; 95%CI:1.09–3.08), but the association was lost when vascular covariates were added to the model. FBG was not associated with aMCI status vs. NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B (p=0.003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (χ2=13.9, p<0.001). Conclusions Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia. PMID:21044774

Comparison of characteristics observed in tinnitus patients with unilateral vs bilateral symptoms, with both normal hearing threshold and distortion-product otoacoustic emissions.

PubMed

Zagólski, Olaf; Stręk, Paweł

2017-02-01

Tinnitus characteristics in normal-hearing patients differ between the groups with unilateral and bilateral complaints. The study was to determine the differences between tinnitus characteristics observed in patients with unilateral vs bilateral symptoms and normal hearing threshold, as well as normal results of distortion-product otoacoustic emissions (DPOAEs). The patients answered questions concerning tinnitus duration, laterality, character, accompanying symptoms, and circumstances of onset. The results of tympanometry, auditory brainstem responses, tinnitus likeness spectrum, minimum masking level (MML), and uncomfortable loudness level were evaluated. Records of 380 tinnitus sufferers were examined. Patients with abnormal audiograms and/or DPOAEs were excluded. The remaining 66 participants were divided into groups with unilateral and bilateral tinnitus. Unilateral tinnitus in normal-hearing patients was diagnosed twice more frequently than bilateral. Tinnitus pitch was higher in the group with bilateral tinnitus (p < .001). MML was lower in unilateral tinnitus (p < .05). Mean age of patients was higher in the unilateral tinnitus group (p < .05). Mean tinnitus duration was longer (p < .05) and hypersensitivity to sound was more frequent (p < .05) in the bilateral tinnitus group. Repeated exposure to excessive noise was the most frequent cause in the bilateral tinnitus group.

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PubMed

Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques

2011-09-01

The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis

PubMed Central

Kim, Sung-Jo; Kang, Sun-Yang; Yi, Jin Woong; Kim, Seung-Min

2014-01-01

Purpose Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients. Methods We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the KCa channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels. PMID:25379045

Impaired leptin expression and abnormal response to fasting in corticotropin-releasing hormone-deficient mice.

PubMed

Jeong, Kyeong-Hoon; Sakihara, Satoru; Widmaier, Eric P; Majzoub, Joseph A

2004-07-01

Leptin has been postulated to comprise part of an adipostat, whereby during states of excessive energy storage, elevated levels of the hormone prevent further weight gain by inhibiting appetite. A physiological role for leptin in this regard remains unclear because the presence of excessive food, and therefore the need to restrain overeating under natural conditions, is doubtful. We have previously shown that CRH-deficient (Crh(-/-)) mice have glucocorticoid insufficiency and lack the fasting-induced increase in glucocorticoid, a hormone important in stimulating leptin synthesis and secretion. We hypothesized that these mice might have low circulating leptin. Indeed, Crh(-/-) mice exhibited no diurnal variation of leptin, whereas normal littermates showed a clear rhythm, and their leptin levels were lower than their counterparts. A continuous peripheral CRH infusion to Crh(-/-) mice not only restored corticosterone levels, but it also increased leptin expression to normal. Surprisingly, 36 h of fasting elevated leptin levels in Crh(-/-) mice, rather than falling as in normal mice. This abnormal leptin change during fasting in Crh(-/-) mice was corrected by corticosterone replacement. Furthermore, Crh(-/-) mice lost less body weight during 24 h of fasting and ate less food during refeeding than normal littermates. Taken together, we conclude that glucocorticoid insufficiency in Crh(-/-) mice results in impaired leptin production as well as an abnormal increase in leptin during fasting, and propose that the fast-induced physiological reduction in leptin may play an important role to stimulate food intake during the recovery from fasting.

Overall survival and self-reported fatigue in patients with esophageal cancer.

PubMed

Stauder, M C; Romero, Y; Kabat, B; Atherton, P J; Geno, D; Deschamps, C; Jatoi, A; Sloan, J A; Botros, M; Jung, K W; Arora, A S; Miller, R C

2013-02-01

A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.

Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

PubMed

Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

2018-01-01

We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Changes of air-tissue ratio evaluated by EBCT after cardiopulmonary resuscitation (CPR): validation in swine

NASA Astrophysics Data System (ADS)

Recheis, Wolfgang A.; Schuster, Antonius H.; Kleinsasser, Axel; Loeckinger, Alexander; Hoermann, Christoph; zur Nedden, Dieter

2001-05-01

The purpose was to evaluate changes of the air-tissue ratio (ATR) in previously defined regions of interest after cardiopulmonary resuscitation (CPR) in porcine model. Eight anesthetized and ventilated pigs we scanned in supine position before and 30 minutes after CPR at two different constant PEEP levels (5 cm H2O, 15 cm H2O). Volume scans were obtained using 6 mm slices. The gray values of the lung were divided into steps of 100 HU in order to get access to the changes of ATR. ATR was evaluated in ventral, intermediate and dorsal regions of the lung. CPR for 9 minutes led to an uneven distribution of ventilation. In the ventral region, areas with high ATR increased. Areas with normal ATR decreased. In contrast the dorsal regions with low ATR increased. ATR in the intermediate regions remained almost unchanged. Using the higher PEEP level, areas with normal ATR showed a marked increase accompanied by a decrease of areas with low ATR. After CPR, an uneven distribution of lung aeration was detected. According to the impaired hemodynamics, areas with normal ATR decreased and areas with high and low ATR increased. Using higher PEEP levels improved lung aeration.

Epoxyeicosanoids promote organ and tissue regeneration.

PubMed

Panigrahy, Dipak; Kalish, Brian T; Huang, Sui; Bielenberg, Diane R; Le, Hau D; Yang, Jun; Edin, Matthew L; Lee, Craig R; Benny, Ofra; Mudge, Dayna K; Butterfield, Catherine E; Mammoto, Akiko; Mammoto, Tadanori; Inceoglu, Bora; Jenkins, Roger L; Simpson, Mary A; Akino, Tomoshige; Lih, Fred B; Tomer, Kenneth B; Ingber, Donald E; Hammock, Bruce D; Falck, John R; Manthati, Vijaya L; Kaipainen, Arja; D'Amore, Patricia A; Puder, Mark; Zeldin, Darryl C; Kieran, Mark W

2013-08-13

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

A role for GPx3 in activity of normal and leukemia stem cells

PubMed Central

Herault, Olivier; Hope, Kristin J.; Deneault, Eric; Mayotte, Nadine; Chagraoui, Jalila; Wilhelm, Brian T.; Cellot, Sonia; Sauvageau, Martin; Andrade-Navarro, Miguel A.; Hébert, Josée

2012-01-01

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs. PMID:22508837

Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma.

PubMed

Fujimoto, Takaaki; Ohtsuka, Takao; Nakashima, Yohei; Gotoh, Yoshitaka; Date, Kenjiro; Mori, Yasuhisa; Sadakari, Yoshihiko; Takahata, Shunichi; Oda, Yoshinao; Nakamura, Masafumi

2017-02-01

Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient.

PubMed

Miyata, T; van Ypersele de Strihou, C; Imasawa, T; Yoshino, A; Ueda, Y; Ogura, H; Kominami, K; Onogi, H; Inagi, R; Nangaku, M; Kurokawa, K

2001-12-01

Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation. Plasma levels of AGEs [pentosidine and Nepsilon-carboxymethyllysine (CML)], their RCO precursors, d-lactate (the final product resulting from the glyoxalase detoxification pathway), as well as of various compounds known to generate AGE precursors and surrogate markers for oxidative stress (antioxidant enzymes and glutathione), were measured in both hemodialysis (HD) patients and normal subjects. The activity and protein expression of glyoxalase I, an enzyme essential for the detoxification of alpha-oxoaldehydes, in red blood cells (RBC) were also examined. In one 69-year-old lady who had been on hemodialysis (HD) for three years and had suffered from recurrent cardiovascular complications despite the absence of significant risk factors, plasma levels of pentosidine (77.3 +/- 2.4 pmol/mg protein) and CML (330.8 +/- 8.2 pmol/mg protein) were markedly elevated as compared to other HD patients (N = 20: 26.6 +/- 11.8 pmol/mg protein for pentosidine and 224.4 +/- 51.7 pmol/mg protein for CML). The plasma level of RCO precursors for pentosidine and CML was also higher in this patient than in other HD patients. Further investigation disclosed a very low activity in RBC of glyoxalase I (1.5 +/- 0.4 mU/106 RBC), as compared to other HD patients (3.9 +/- 0.6 mU/106 RBC) or normal subjects (4.0 +/- 0.6 mU/106 RBC). The glyoxalase I protein level, assessed in RBC by immunoblot analysis with a specific antibody, was markedly lower than that observed in HD patients and normal subjects. The causes of this deficiency remain unknown. Nucleotide sequencing of the products of reverse transcription-polymerase chain reaction from the patient's mononuclear cells revealed no genetic mutation within the coding region of the glyoxalase I gene. Plasma d-lactate level was also in the lower range (0.18 +/- 0.03 mg/dL) of the values measured in the other HD patients (0.27 +/- 0.09 mg/dL) and normal subjects (0.35 +/- 0.12 mg/dL). The plasma levels of various compounds known to generate AGE precursors (glucose, lipids and ascorbic acid) were either normal or low. The surrogate markers for oxidative stress such as antioxidant enzymes (glutathione peroxidases and superoxide dismutase) and glutathione were all within the range observed in the other HD patients. The unusually high levels of AGEs in this patient implicate a deficient glyoxalase detoxification of RCO precursors. The present clinical observation implicates, to our knowledge for the first time, the glyoxalase detoxification system and, in particular, glyoxalase in the actual level of AGEs in a uremic patient.

Geometrically Nonlinear Transient Analysis of Laminated Composite Plates.

DTIC Science & Technology

1982-03-01

theory (CPT), in which normals to the midsurface before deformation are assumed to remain straight and normal to the midsurface after deformation (i.e...the plate are negligible when compared to the inplane stresses, and normals to the plate midsurface before deformation remain straight but not...necessarily normal to the midsurface after deformation. $ Equations of motion The plate under consideration is composed of a finite number of orthotropic

Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones.

PubMed

Vogl, Daniela; Falk, Werner; Dorner, Monika; Schölmerich, Jürgen; Straub, Rainer H

2003-02-01

In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), low levels of adrenal steroids have been repeatedly demonstrated, but the site of alteration has not been exactly described because measurements of serum pregnenolone and 17-hydroxypregnenolone (17OHPreg) together with other adrenal steroids have never been performed. We measured serum levels of adrenal hormones such as pregnenolone, 17OHPreg, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), progesterone (P), 17-hydroxyprogesterone (17OHP), androstenedione (ASD), and cortisol in 24 healthy controls, 24 patients with RA, and 24 patients with SLE. Serum levels of pregnenolone were similar in RA and SLE patients as compared to healthy controls irrespective of prior prednisolone therapy. In all RA and SLE patients (including those with prior prednisolone treatment), serum levels of all measured hormones except pregnenolone were significantly lower as compared to controls. In RA patients without prior prednisolone treatment, serum levels of 17OHPreg, DHEA, cortisol, and ASD were similar to controls, and serum levels of P, 17OHP, and DHEAS were significantly lower as compared to controls. In SLE patients without prior prednisolone treatment, serum levels of 17OHPreg and cortisol were similar, and serum levels of P, 17OHP, ASD, DHEA, and DHEAS were significantly lower as compared to controls. The primary hormone of the adrenal steroid cascade, pregnenolone, is almost normal in RA and SLE irrespective of corticosteroid treatment. In patients with RA, we believe that there is a near normal P450scc reaction and a normal double step P450c17 reaction. In SLE patients, the P450scc reaction also seems normal but the second step of the P450c17 reaction seems to be inhibited. In both diseases, cortisol levels remain relatively stable at the expense of other adrenal hormones. This study revealed distinct changes of steroid pathways that are related to the disease entities.

Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat.

PubMed

Laskowska-Macios, Karolina; Zapasnik, Monika; Hu, Tjing-Tjing; Kossut, Malgorzata; Arckens, Lutgarde; Burnat, Kalina

2015-10-01

Pattern vision deprivation (BD) can induce permanent deficits in global motion perception. The impact of timing and duration of BD on the maturation of the central and peripheral visual field representations in cat primary visual areas 17 and 18 remains unknown. We compared early BD, from eye opening for 2, 4, or 6 months, with late onset BD, after 2 months of normal vision, using the expression pattern of the visually driven activity reporter gene zif268 as readout. Decreasing zif268 mRNA levels between months 2 and 4 characterized the normal maturation of the (supra)granular layers of the central and peripheral visual field representations in areas 17 and 18. In general, all BD conditions had higher than normal zif268 levels. In area 17, early BD induced a delayed decrease, beginning later in peripheral than in central area 17. In contrast, the decrease occurred between months 2 and 4 throughout area 18. Lack of pattern vision stimulation during the first 4 months of life therefore has a different impact on the development of areas 17 and 18. A high zif268 expression level at a time when normal vision is restored seems to predict the capacity of a visual area to compensate for BD. © The Author 2014. Published by Oxford University Press.

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

PubMed

Hay, Cathy J; Brady, Brian M; Zitzmann, Michael; Osmanagaoglu, Kaan; Pollanen, Pasi; Apter, Dan; Wu, Frederick C W; Anderson, Richard A; Nieschlag, Eberhard; Devroey, Paul; Huhtaniemi, Ilpo; Kersemaekers, Wendy M

2005-04-01

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Nocturnal levels of chemerin and progranulin in adolescents: influence of sex, body mass index, glucose metabolism and sleep.

PubMed

Daxer, Johann; Herttrich, Theresa; Zhao, Ying Y; Vogel, Mandy; Hiemisch, Andreas; Scheuermann, Kathrin; Körner, Antje; Kratzsch, Jürgen; Kiess, Wieland; Quante, Mirja

2017-01-01

Adipokines have been implicated in obesity, insulin resistance and sleep regulation. However, the role of chemerin and progranulin, two recently described adipokines, in the context of sleep remains unclear. The aim of this study was to compare nocturnal serum chemerin and progranulin levels between overweight/obese and normal-weight adolescents and to assess variations by sex, across different sleep stages and in relation to glucose metabolism. The study sample included 34 overweight/obese and 32 normal-weight adolescents from secondary schools and the Leipzig Research Center for Civilization Diseases (LIFE) Child study cohort. We obtained longitudinal serum adipokine levels during in-laboratory polysomnography followed by an oral glucose tolerance test. Overweight/obese adolescents had significantly higher mean nocturnal serum chemerin area under the curve (AUC) levels (348.2±133.3 vs. 241.7±67.7 vs. ng/mL×h, p<0.001) compared to normal-weight controls. In detail, higher chemerin AUC levels in obese/overweight subjects were exclusively due to increased levels in females. No overall difference for serum progranulin AUC was found between the groups. However, when assessing sex-specific levels, serum progranulin AUC levels were ~30% higher in overweight/obese males compared to overweight/obese females. Of note, nocturnal serum chemerin and progranulin AUC did not exhibit a correlation with markers of glucose metabolism or sleep stages. Collectively, we report a sexual dimorphism in nocturnal progranulin and chemerin levels, which may help explain underlying differences in energy balance and body composition between males and females in the context of obesity.

Somatotroph Hyperplasia

PubMed Central

Thorner, M. O.; Perryman, R. L.; Cronin, M. J.; Rogol, A. D.; Draznin, M.; Johanson, A.; Vale, W.; Horvath, E.; Kovacs, K.

1982-01-01

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95±9.4 ng/ml; mean±SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm3) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified. Images PMID:6290540

Follow-up of newborns of mothers with Graves' disease.

PubMed

Levy-Shraga, Yael; Tamir-Hostovsky, Liran; Boyko, Valentina; Lerner-Geva, Liat; Pinhas-Hamiel, Orit

2014-06-01

Overt neonatal Graves' disease is rare, but may be severe, even life threatening, with deleterious effects on neural development. The main objective of this study was to describe the course of thyrotropin (TSH) and free thyroxin (fT4) levels, as well as postnatal weight gain in relation to fT4 levels, in neonates born to women with Graves' disease without overt neonatal thyrotoxicosis. Such information is important to deduce the optimal schedule for evaluation. We conducted a retrospective chart review of neonates born to mothers with Graves' disease between January 2007 and December 2012. The records were reviewed for sex, gestational age, birth weight, maternal treatment during pregnancy, and maternal thyroid stimulating immunoglobulin (TSI) level. For each visit in the clinic, the data included growth parameters, presence of symptoms suspected for hyperthyroidism, blood test results (levels of TSH, fT4, and TSI), and treatment. Ninety-six neonates were included in the study (49 males), with a total of 320 measurements of thyroid function tests (TSH and fT4). Four neonates (4%) had overt neonatal Graves' disease; one of them along with nine others were born preterm. In 77 (92.9%) of the remaining 83 neonates (the subclinical group), fT4 levels were above the 95th percentile on day 5. All had normal fT4 on day 15. A negative association was found between fT4 and weight gain during the first two weeks. In this cohort, most neonates born to mothers with Graves' disease had a subclinical course with abnormal fT4 levels that peaked at day 5. After day 14, all measurements of fT4 returned to the normal range, although measurements of TSH remained suppressed for up to three months. Elevated fT4 was associated with poor weight gain.

Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Decomposition in Different Microclimate Conditions.

PubMed

Unger, K A; Watterson, J H

2016-10-01

The effects of decomposition microclimate on the distribution of dextromethorphan (DXM) and dextrorphan (DXT) in skeletonized remains of rats acutely exposed to DXM were examined. Animals (n = 10) received DXM (75 mg/kg, i.p.), were euthanized 30 min post-dose and immediately allowed to decompose at either Site A (shaded forest microenvironment on a grass-covered soil substrate) or Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Ambient temperature and relative humidity were automatically recorded 3 cm above rats at each site. Skeletal elements (vertebral columns, ribs, pelvic girdles, femora, tibiae, humeri and scapulae) were harvested, and analyzed using microwave assisted extraction, microplate solid phase extraction, and GC/MS. Drug levels, expressed as mass-normalized response ratios, and the ratios of DXT and DXM levels were compared across bones and between microclimate sites. No significant differences in DXT levels or metabolite/parent ratios were observed between sites or across bones. Only femoral DXM levels differed significantly between microclimate sites. For pooled data, microclimate was not observed to significantly affect analyte levels, nor the ratio of levels of DXT and DXM. These data suggest that microclimate conditions do not influence DXM and metabolite distribution in skeletal remains. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD).

PubMed

Wölfl, Christoph; Schweppenhäuser, Daniela; Gühring, Thorsten; Takur, Caner; Höner, Bernd; Kneser, Ulrich; Grützner, Paul Alfred; Kolios, Leila

2014-01-01

The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor β1 (TGFβ1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.

Premature aging/senescence in cancer cells facing therapy: good or bad?

PubMed

Gonzalez, Llilians Calvo; Ghadaouia, Sabrina; Martinez, Aurélie; Rodier, Francis

2016-02-01

Normal and cancer cells facing their demise following exposure to radio-chemotherapy can actively participate in choosing their subsequent fate. These programmed cell fate decisions include true cell death (apoptosis-necroptosis) and therapy-induced cellular senescence (TIS), a permanent "proliferative arrest" commonly portrayed as premature cellular aging. Despite a permanent loss of proliferative potential, senescent cells remain viable and are highly bioactive at the microenvironment level, resulting in a prolonged impact on tissue architecture and functions. Cellular senescence is primarily documented as a tumor suppression mechanism that prevents cellular transformation. In the context of normal tissues, cellular senescence also plays important roles in tissue repair, but contributes to age-associated tissue dysfunction when senescent cells accumulate. Theoretically, in multi-step cancer progression models, cancer cells have already bypassed cellular senescence during their immortalization step (see hallmarks of cancer). It is then perhaps surprising to find that cancer cells often retain the ability to undergo TIS, or premature aging. This occurs because cellular senescence results from multiple signalling pathways, some retained in cancer cells, aiming to prevent cell cycle progression in damaged cells. Since senescent cancer cells persist after therapy and secrete an array of cytokines and growth factors that can modulate the tumor microenvironment, these cells may have beneficial and detrimental effects regarding immune modulation and survival of remaining proliferation-competent cancer cells. Similarly, while normal cells undergoing senescence are believed to remain indefinitely growth arrested, whether this is true for senescent cancer cells remains unclear, raising the possibility that these cells may represent a reservoir for cancer recurrence after treatment. This review discusses our current knowledge on cancer cell senescence and highlight questions that must be addressed to fully understand the beneficial and detrimental impacts of cellular senescence during cancer therapy.

Impact of Body Mass Index on Plasma N-Terminal ProB-Type Natriuretic Peptides in Chinese Atrial Fibrillation Patients without Heart Failure

PubMed Central

Zheng, Li-hui; Wu, Ling-min; Yao, Yan; Chen, Wen-sheng; Bao, Jing-ru; Huang, Wen; Shi, Rui; Zhang, Kui-jun; Zhang, Shu

2014-01-01

Background An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure. Methods A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m2) and normal weight (BMI<25 kg/m2) patients. Results Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level. Conclusions An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients. PMID:25144363

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

PubMed

Takano, Toru; Miyauchi, Akira; Ito, Yasuhiro; Amino, Nobuyuki

2006-06-01

We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase.

PubMed

Wirth, Eva K; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-09-01

The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

Prolonged spontaneous normocalcaemia in pseudohypoparathyroidism from resorption of soft tissue calcium deposits: a cautionary tale

PubMed Central

Carter, Erin E; Kline, Gregory

2014-01-01

A 42-year-old man diagnosed with pseudohypoparathyroidism and Albright's hereditary osteodystrophy as an infant was lost to follow-up and remained, unmonitored, on calcitriol and calcium for over 20 years. He presented after having an ST-elevation myocardial infarction. In addition to coronary artery calcifications, he was found to have diffuse subcutaneous and joint calcifications. His calcium, phosphate and parathyroid hormone (PTH) levels were normal, and given the lack of prior documentation in the diagnosis he was instructed to discontinue calcitriol and calcium until further investigations were completed. Despite stopping the medication, his serum calcium remained normal for over 1 year. It was not until 18 months later, when his soft tissue calcium stores were depleted, that he finally developed symptomatic hypocalcaemia and an elevated PTH. This case not only emphasises the importance of long-term follow-up for patients with pseudohypoparathyroidism, but also highlights the potential complications of long-term, unmonitored, calcitriol use. PMID:24481017

Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

PubMed

Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

2005-01-01

To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic information in patients with known or suspected residual tumor. BMD should be assessed at both appendicular and axial sites in patients with persistent tumor-induced osteomalacia.

Symptomatic Hypercalcemia in a Patient with B-cell Chronic Lymphocytic Leukemia - A Case Report and Review of the Literature.

PubMed

Koutroumpakis, Efstratios; Lobe, Montgomery; McCarthy, Lezah; Mehdi, Syed

Hypercalcemia due to malignancy is well described in the literature and a common paraneoplastic finding in certain solid tumors. Hematologic malignancies, however, are less frequently associated with hypercalcemia with the exception of myelomas and T-cell lymphomas. This case report describes a patient with B-cell chronic lymphocytic leukemia (B-CLL) who developed symptomatic hypercalcemia. None of the pathogenetic mechanisms of malignancy-associated hypercalcemia already described in the literature could explain the pathogenesis of hypercalcemia in our patient. Calcium levels were normalized after initial treatment and remained within normal limits following treatment of the underlying B-CLL. The follow-up period was 26 months. The normalization of calcium levels was closely associated with the drop in the absolute lymphocyte count. Symptomatic hypercalcemia in B-CLL is exceedingly rare and only documented a few times in the literature. Hypercalcemia, in the present case, was not caused by any of the mechanisms already described in the literature and responded well to treatment of the underlying B-CLL. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Partial anterior cruciate ligament tears treated with intraligamentary plasma rich in growth factors

PubMed Central

Seijas, Roberto; Ares, Oscar; Cuscó, Xavier; Álvarez, Pedro; Steinbacher, Gilbert; Cugat, Ramón

2014-01-01

AIM: To evaluate the effect of the application of plasma rich in growth factors (PRGF)-Endoret to the remaining intact bundle in partial anterior cruciate ligament (ACL) tears. METHODS: A retrospective review of the rate of return to play in football players treated with the application of PRGF-Endoret in the remaining intact bundle in partial ACL injuries that underwent surgery for knee instability. Patients with knee instability requiring revision surgery for remnant ACL were selected. PRGF was applied in the wider part of posterolateral bundle and the time it took patients to return to their full sporting activities at the same level before the injury was evaluated. RESULTS: A total of 19 patients were reviewed. Three had a Tegner activity level of 10 and the remaining 16 level 9. The time between the injury and the time of surgery was 5.78 wk (SD 1.57). In total, 81.75% (16/19) returned to the same pre-injury level of sport activity (Tegner 9-10). 17 males and 2 females were treated. The rate of associated injury was 68.42% meniscal lesions and 26.31% cartilage lesions. The KT-1000 values were normalized in all operated cases. One patient was not able to return to sport due to the extent of their cartilage lesions. The 15 patients with Tegner activity level 9 returned to play at an average of 16.20 wk (SD 1.44) while the 3 patients with Tegner activity level 10 did so in 12.33 wk (SD 1.11). CONCLUSION: With one remaining intact bundle the application of PRGF-Endoret in instability cases due to partial ACL tear showed high return to sport rates at pre- injury level in professional football players. PMID:25035842

Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.

PubMed

Tietze, Julia K; Angelova, Daniela; Heppt, Markus V; Ruzicka, Thomas; Berking, Carola

2017-07-01

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 dim and CD56 bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 dim NK cells, whereas the baseline levels of CD56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 dim and CD56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 dim NK cells as well as normal baseline levels of CD56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56 dim and CD56 bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting

PubMed Central

Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

2013-01-01

OBJECTIVES High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG. METHODS Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft–Gault equation: 1339 patients with estimated GFR of ≥60 ml/min/1.73 m2 (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m2 (ORI group). RESULTS Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m2, P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16–2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16–2.02], P < 0.01). CONCLUSIONS ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels. PMID:23793709

Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting.

PubMed

Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

2013-10-01

High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG. Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft-Gault equation: 1339 patients with estimated GFR of ≥ 60 ml/min/1.73 m(2) (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m(2) (ORI group). Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m(2), P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16-2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16-2.02], P < 0.01). ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels.

Personality dimensions in bulimia nervosa, binge eating disorder, and obesity.

PubMed

Peterson, Carol B; Thuras, Paul; Ackard, Diann M; Mitchell, James E; Berg, Kelly; Sandager, Nora; Wonderlich, Stephen A; Pederson, Melissa W; Crow, Scott J

2010-01-01

The purpose of this investigation was to examine differences in personality dimensions among individuals with bulimia nervosa, binge eating disorder, non-binge eating obesity, and a normal-weight comparison group as well as to determine the extent to which these differences were independent of self-reported depressive symptoms. Personality dimensions were assessed using the Multidimensional Personality Questionnaire in 36 patients with bulimia nervosa, 54 patients with binge eating disorder, 30 obese individuals who did not binge eat, and 77 normal-weight comparison participants. Participants with bulimia nervosa reported higher scores on measures of stress reaction and negative emotionality compared to the other 3 groups and lower well-being scores compared to the normal-weight comparison and the obese samples. Patients with binge eating disorder scored lower on well-being and higher on harm avoidance than the normal-weight comparison group. In addition, the bulimia nervosa and binge eating disorder groups scored lower than the normal-weight group on positive emotionality. When personality dimensions were reanalyzed using depression as a covariate, only stress reaction remained higher in the bulimia nervosa group compared to the other 3 groups and harm avoidance remained higher in the binge eating disorder than the normal-weight comparison group. The higher levels of stress reaction in the bulimia nervosa sample and harm avoidance in the binge eating disorder sample after controlling for depression indicate that these personality dimensions are potentially important in the etiology, maintenance, and treatment of these eating disorders. Although the extent to which observed group differences in well-being, positive emotionality, and negative emotionality reflect personality traits, mood disorders, or both, is unclear, these features clearly warrant further examination in understanding and treating bulimia nervosa and binge eating disorder.

Role of Krüppel-like factor 4 and heat shock protein 27 in cancer of the larynx

PubMed Central

Karam, Jihad; Fadous-Khalifé, Marie Claude; Tannous, Rita; Fakhreddine, Sally; Massoud, Marcel; Hadchity, Joseph; Aftimos, Georges; Hadchity, Elie

2017-01-01

Late detection and lack of standard treatment strategies in larynx cancer patients result in high levels of mortality and poor prognosis. Prognostic stratification of larynx cancer patients based on molecular prognostic tumor biomarkers may lead to more efficient clinical management. Krüppel-like factor 4 (KLF4) and Heat Shock Protein 27 (HSP27) have an important role in tumorigenesis and are considered promising candidate biomarkers for various types of cancer. However, their role in larynx carcinoma remains to be elucidated. The present study aimed to determine KLF4 and HSP27 expression profiles in laryngeal tumors. The protein and mRNA expression levels of KLF4 and HSP27 were evaluated by immunohistochemical and reverse transcription-polymerase chain reaction analyses in 44 larynx carcinoma samples and 21 normal tissue samples, and then correlated with clinical characteristics. A differential expression of KLF4 and HSP27 was observed between normal and tumor tissues. The protein and mRNA expression levels of KLF4 were significantly decreased in larynx squamous cell carcinoma (LSCC) compared with normal tissue, whereas HSP27 was significantly overexpressed in tumor tissues compared with normal tissues, at the protein and mRNA levels. KLF4 expression decreased gradually with tumor progression whereas HSP27 expression increased. A significant difference was observed between stages I and IV. KLF4 and HSP27 exhibit opposite functions and roles in the carcinogenic process of LSCC. Their role in laryngeal cancer initiation and progression emphasizes their use as potential future targets for prognosis and treatment. KLF4 and HSP27 expression levels may act as potential biomarkers in patients with cancer of the larynx. PMID:29181170

Extensions, Validation, and Clinical Applications of a Feedback Control System Simulator of the Hypothalamo-Pituitary-Thyroid Axis

PubMed Central

Samuels, Mary; DiStefano, Joseph J.

2008-01-01

Background We upgraded our recent feedback control system (FBCS) simulation model of human thyroid hormone (TH) regulation to include explicit representation of hypothalamic and pituitary dynamics, and updated TH distribution and elimination (D&E) parameters. This new model greatly expands the range of clinical and basic science scenarios explorable by computer simulation. Methods We quantified the model from pharmacokinetic (PK) and physiological human data and validated it comparatively against several independent clinical data sets. We then explored three contemporary clinical issues with the new model: combined triiodothyronine (T3)/thyroxine (T4) versus T4-only treatment, parenteral levothyroxine (L-T4) administration, and central hypothyroidism. Results Combined T3/T4 therapy—In thyroidectomized patients, the L-T4–only replacement doses needed to normalize plasma T3 or average tissue T3 were 145 μg L-T4/day or 165 μgL-T4/day, respectively. The combined T4 + T3 dosing needed to normalize both plasma and tissue T3 levels was 105 μg L-T4 + 9 μgT3 per day. For all three regimens, simulated mean steady-state plasma thyroid-stimulating hormone (TSH), T3, and T4 was within normal ranges (TSH: 0.5–5 mU/L; T4: 5–12 μg/dL; T3: 0.8–1.9 ng/mL). Parenteral T4 administration—800 μg weekly or 400 μg twice weekly normalized average tissue T3 levels both for subcutaneous (SC) and intramuscular (IM) routes of administration. TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM). Central hypothyroidism—We simulated steady-state plasma T3,T4, and TSH concentrations in response to varying degrees of central hypothyroidism, reducing TSH secretion from 50% down to 0.1% of normal. Surprisingly, TSH, T3, and T4 plasma concentrations remained within normal ranges for TSH secretion as low as 25% of normal. Conclusions Combined T3/T4 treatment—Simulated standard L-T4–only therapy was sufficient to renormalize average tissue T3 levels and maintain normal TSH, T3, and T4 plasma levels, supporting adequacy of standard L-T4–only treatment. Parenteral T4 administration—TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM), supporting these therapeutic alternatives for patients with compromised L-T4 gut absorption. Central hypothyroidism—These results highlight how highly nonlinear feedback in the hypothalamic-pituitary-thyroid axis acts to maintain normal hormone levels, even with severely reduced TSH secretion. PMID:18844475

Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease.

PubMed

Wolf, Myles; White, Kenneth E

2014-07-01

High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

Diabetes mellitus with normal renal function is associated with anaemia.

PubMed

Grossman, Chagai; Dovrish, Zamir; Koren-Morag, Nira; Bornstein, Gil; Leibowitz, Avshalom

2014-05-01

Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min]. The charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five subjects with type 2 DM and normal renal function were indentified and compared with those without DM who were routinely examined at the same time. Subjects' electronic records were used to build a biochemical and clinical database. Mean haemoglobin levels were lower in subjects with DM than in those without (14.2 vs. 14.7 g/dL, respectively; p < 0.001). Anaemia was observed in 48 (10.8%) subjects in the diabetic group and in only 12 (2.7%) in the nondiabetic group (p < 0.001). Multivariate analysis revealed that age, gender, history of gastrointestinal disease, use of beta blockers, renal function and DM were independent determinants of haemoglobin levels. After adjustment for age, gender, history of gastrointestinal tract diseases and renal function, DM remained a significant determinant of anaemia with an odds ratio of 2.15 (confidence interval: 1.07-4.31). Anaemia is more common in diabetic patients even when eGFR > 60 mL/min. Copyright © 2013 John Wiley & Sons, Ltd.

Evaluation of the Pharmacokinetics and Tolerance of Allopurinol Riboside in Human Volunteers.

DTIC Science & Technology

1984-08-06

hepatitis B "e" antigen. In addition, a mononucleosis screen was performed on serum. Urine and blood (buffy coat) were cultured for cytomegalovirus (CMV...study. His enzyme levels returned to norma, in two weeks, and remained normal one week thereafter. The following laboratory tests for infectious ...hepatitis were negative: hepatitis B surface antigen and antibody, hepatitis B core antibody, hepatitis A antibody, mononucleosis spot test, VDRL

BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section.

PubMed

Meng, Lingbin; Huang, Tao; Sun, Chengsan; Hill, David L; Krimm, Robin

2017-07-01

Taste nerves readily regenerate to reinnervate denervated taste buds; however, factors required for regeneration have not yet been identified. When the chorda tympani nerve is sectioned, expression of brain-derived neurotrophic factor (BDNF) remains high in the geniculate ganglion and lingual epithelium, despite the loss of taste buds. These observations suggest that BDNF is present in the taste system after nerve section and may support taste nerve regeneration. To test this hypothesis, we inducibly deleted Bdnf during adulthood in mice. Shortly after Bdnf gene recombination, the chorda tympani nerve was unilaterally sectioned causing a loss of both taste buds and neurons, irrespective of BDNF levels. Eight weeks after nerve section, however, regeneration was differentially affected by Bdnf deletion. In control mice, there was regeneration of the chorda tympani nerve and taste buds reappeared with innervation. In contrast, few taste buds were reinnervated in mice lacking normal Bdnf expression such that taste bud number remained low. In all genotypes, taste buds that were reinnervated were normal-sized, but non-innervated taste buds remained small and atrophic. On the side of the tongue contralateral to the nerve section, taste buds for some genotypes became larger and all taste buds remained innervated. Our findings suggest that BDNF is required for nerve regeneration following gustatory nerve section. Copyright © 2017 Elsevier Inc. All rights reserved.

Surges in proteinuria are associated with plasma GL-3 elevations in a young patient with classic Fabry disease.

PubMed

Kanai, Takahiro; Ito, Takane; Odaka, Jun; Saito, Takashi; Aoyagi, Jun; Betsui, Hiroyuki; Yamagata, Takanori

2016-03-01

Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy progresses. Recombinant agalsidase replacement therapy is currently the only approved, specific therapy for Fabry disease. The optimal dose of replacement enzyme also still remains unclear. The worldwide shortage of agalsidase-β in 2009 forced dose reduction of administration. It showed that the proteinuria emerged like surges, followed by temporary plasma GL-3 elevations in the early stages of classic Fabry disease. Additionally, it also showed that 1 mg/kg of agalsidase-β every other week could clear the GL-3 accumulations from podocytes and was required to maintain negative proteinuria and normal plasma GL-3 levels. This observation of a young patient with classic Fabry disease about 5 years reveals that the long-term, low-dose agalsidase-β caused proteinuria surges, but not persistent proteinuria, followed by temporary plasma GL-3 elevations, and agalsidase-β at 1 mg/kg every other week could clear accumulated GL-3 from podocytes and was required to maintain normal urinalysis and plasma GL-3 levels.

Iron promotes protein insolubility and aging in C. elegans.

PubMed

Klang, Ida M; Schilling, Birgit; Sorensen, Dylan J; Sahu, Alexandria K; Kapahi, Pankaj; Andersen, Julie K; Swoboda, Peter; Killilea, David W; Gibson, Bradford W; Lithgow, Gordon J

2014-11-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity ofCaenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation.

Tenascin-C is not a useful marker for disease activity in psoriasis.

PubMed

Latijnhouwers, M A; Bergers, M; Kuijpers, A L; van der Vleuten, C J; Dijkman, H; van de Kerkhof, P C; Schalkwijk, J

1998-09-01

Tenascin-C is an extracellular matrix glycoprotein that is markedly upregulated in the dermis of psoriatic skin. In this study, we have addressed the question whether the presence of tenascin-C in the lesion or in serum is a marker for disease activity. Immunohistochemical staining of tenascin-C before and after treatment with different topical and systemic medication showed that tenascin-C remained abundant after clinical remission of lesions, indicating that downregulation of tenascin-C to normal values is a slow process. By using a sensitive enzyme-linked immunosorbent assay to measure levels of serum tenascin-C in psoriatic patients and unaffected individuals, we found that tenascin-C levels in most patients were within the normal range. Moreover, tenascin-C values did not correlate with disease activity. We conclude that tenascin-C is not useful as a marker for disease activity in psoriasis.

Central auditory neurons have composite receptive fields.

PubMed

Kozlov, Andrei S; Gentner, Timothy Q

2016-02-02

High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes.

Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

NASA Technical Reports Server (NTRS)

Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

2002-01-01

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes.

PubMed

Parikh, Sameer A; Leis, Jose F; Chaffee, Kari G; Call, Timothy G; Hanson, Curtis A; Ding, Wei; Chanan-Khan, Asher A; Bowen, Deborah; Conte, Michael; Schwager, Susan; Slager, Susan L; Van Dyke, Daniel L; Jelinek, Diane F; Kay, Neil E; Shanafelt, Tait D

2015-09-01

Although hypogammaglobulinemia is a well recognized complication in patients with chronic lymphocytic leukemia (CLL), its prevalence at the time of CLL diagnosis, and association with novel prognostic markers and clinical outcome is not well understood. All patients at the Mayo Clinic between January 1999 and July 2013 who had newly diagnosed CLL and had a baseline assessment of serum immunoglobulin G (IgG) were included. The relation between hypogammaglobulinemia at diagnosis and the novel prognostic parameters time to first treatment (TFT) and overall survival (OS) were evaluated. Of 1485 patients who met the eligibility criteria, 382 (26%) had hypogammaglobulinemia (median IgG, 624 mg/dL), whereas the remaining 1103 patients (74%) had normal serum IgG levels (median IgG, 1040 mg/dL). Patients who had hypogammaglobulinemia at diagnosis were more likely to have advanced Rai stage (III-IV; P = .001) and higher expression of CD49d (P < .001) compared with patients who had normal IgG levels. Although the median TFT for patients who had hypogammaglobulinemia was shorter compared with that for patients who had normal IgG levels (3.8 years vs 7.4 years; P < .001), on multivariable analysis, there was no difference in OS between these 2 groups (12.8 years vs 11.3 years, respectively; P = .73). Of 1103 patients who had CLL with normal IgG levels at diagnosis and who did not receive CLL therapy, the risk of acquired hypogammaglobulinemia was 11% at 5 years and 23% at 10 years. Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long-term follow-up. The presence of hypogammaglobulinemia does not appear to impact overall survival. © 2015 American Cancer Society.

Ghrelin acts as energy status sensor of male reproduction by modulating Sertoli cells glycolytic metabolism and mitochondrial bioenergetics.

PubMed

Martins, A D; Sá, R; Monteiro, M P; Barros, A; Sousa, M; Carvalho, R A; Silva, B M; Oliveira, P F; Alves, M G

2016-10-15

Ghrelin is a growth hormone-releasing peptide that has been suggested to interfere with spermatogenesis, though the underling mechanisms remain unknown. We studied the effect of ghrelin in human Sertoli cells (hSCs) metabolic phenotype. For that, hSCs were exposed to increasing concentrations of ghrelin (20, 100 and 500 pM) mimicking the levels reported in obese, normal weight, and severely undernourished individuals. The metabolite production/consumption was determined. The protein levels of key glycolysis-related transporters and enzymes were assessed. The lactate dehydrogenase (LDH) activity was measured. Mitochondrial complexes protein levels and mitochondria membrane potential were also measured. We showed that hSCs express the growth hormone secretagogue receptor. At the concentration present in the plasma of normal weight men, ghrelin caused a decrease of glucose consumption and mitochondrial membrane potential in hSCs, though LDH activity and lactate production remained unchanged, illustrating an alteration of glycolytic flux efficiency. Exposure of hSCs to levels of ghrelin found in the plasma of severely undernourished individuals decreased pyruvate consumption and mitochondrial complex III protein expression. All concentrations of ghrelin decreased alanine and acetate production by hSCs. Notably, the effects of ghrelin levels found in severely undernourished individuals were more pronounced in hSCs metabolic phenotype highlighting the importance of a proper eating behavior to maintain male reproductive potential. In conclusion, ghrelin acts as an energy status sensor for hSCs in a dose-dependent manner, showing an inverse association with the production of lactate, thus controlling the nutritional support of spermatogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

PubMed Central

Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

2015-01-01

The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

Short Communication: Lack of Immune Response in Rapid Progressor Morphine-Dependent and SIV/SHIV-Infected Rhesus Macaques Is Correlated with Downregulation of TH1 Cytokines

PubMed Central

Kumar, Rakesh; Noel, Richard J.; Garcia, Yashira; Rodriguez, Idia V.; Martinez, Melween; Sariol, Carlos A.; Kraiselburd, Edmundo; Iszard, Marcus; Mukherji, Mridul; Kumar, Santosh; Giavedoni, Luis D.; Kumar, Anil

2010-01-01

Abstract Our previous studies have shown two distinct disease patterns (rapid and normal onset of clinical symptoms) in morphine-dependent SHIV/SIV-inoculated rhesus macaques. We have also shown that control as well as 50% of morphine-dependent macaques (normal progressor) developed humoral and cellular immune responses whereas the other half of the morphine-dependent macaques (rapid progressor) did not develop antiviral immune responses after infection with SIV/SHIV. In the present study, we analyzed the association between cytokine production, immune response, and disease progression. To study the immunological effects of morphine at cytokine levels in the context of a lentiviral infection, we inoculated rhesus macaques with a mixture of SHIVKU−18, SHIV89.6P, and SIV/17E-Fr. These animals were followed for a period of 56 weeks for cytokine level production in plasma. Drug-dependent rapid disease progressors exhibited an increase in IL-18 and IL-1Ra and a decrease in IL-12 levels in the plasma. Morphine-dependent normal progressors and control macaques exhibited an increase in both IL-18 and IL-12, whereas IL-Ra levels remained constant throughout the observation period. These results suggest that rapid disease progression in relation to morphine dependency may be the result of an altered cytokine profile. PMID:20672973

Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum.

PubMed

De Luca, Arnaud; Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J; Ingrand, Pierre; Hankard, Régis

2016-01-01

Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period.

Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity.

PubMed

Chen, Jiaxi; Li, Shuang; Shi, Jianfeng; Zhang, Lili; Li, Jun; Chen, Shiyong; Wu, Chunlong; Shen, Bo

2016-03-01

Soluble progranulin (PGRN) is known to directly regulate regulatory T cells; however, whether PGRN levels are elevated in patients with rheumatoid arthritis and affect the regulatory subsets of B cells remain unknown. In this study, a total of 80 RA patients and 60 healthy controls were studied. Serum progranulin levels were determined using enzyme-linked immune-sorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of serum PGRN as a biomarker for distinguishing patients with RA. CD19(+)CD5(+)GrB(+) B cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). Serum progranulin levels in RA patients (median, 59.4 ng/mL) and in RA patients DAS28 > 5.1 (median, 71.98 ng/mL) were much higher than those in normal controls (median, 46.3 ng/mL; P < 0.001). The area under the ROC curve for progranulin levels was 0.705 for RA versus normal controls and the area under the ROC curve for progranulin levels in RA patients DAS28 > 5.1 was 0.977 versus normal controls (P < 0.001). Interestingly, serum progranulin and DAS28, CRP, ESR were all positively correlated in RA patients (P < 0.001). The number of CD19(+)CD5(+)GrB(+) B cells was significantly higher in RA patients (P < 0.05); however, the level of Breg cells was not related to PGRN (P > 0.05). Our findings indicated that induction of PGRN expression may play a role in RA immune reaction and PGRN levels could be a useful biomarker in RA inflammatory response, but irrelated with Breg cell levels.

Increased 2,3-diphosphoglycerate during normocapnic hypobaric hypoxia.

PubMed

Cymerman, A; Maher, J T; Cruz, J C; Reeves, J T; Denniston, J C; Grover, R F

1976-10-01

The effect of 96 h of exposure to hypobaric hypoxia with and without 3.8% CO2 supplementation was studied in two groups of subjects. Five subjects (CO2) were exposed to 440-465 mm Hg barometric pressure (4000-4400 m), and 4 subjects (no-CO2) were exposed to 455-492 mm Hg (3500-1400 m) in order to produce similar levels of resting end-tidal PO2. After 24 h, 2,3-DPG levels of both groups significantly increased and remained elevated. The CO2 group had higher levels than the non-CO2 group after 48 and 72 h. Concurrent measurements of P50 showed similar changes over the same time course. Mean corpuscular hemoglobin concentrations remained normal for 48 h and then decreased in both groups, the CO2 group showing the larger decrease. We conclude that altitude exposure may produce an increase in 2,3-DPG without the presence of respiratory alkalosis previously thought necessary.

Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis.

PubMed

Khajuria, Rajiv K; Munschauer, Mathias; Ulirsch, Jacob C; Fiorini, Claudia; Ludwig, Leif S; McFarland, Sean K; Abdulhay, Nour J; Specht, Harrison; Keshishian, Hasmik; Mani, D R; Jovanovic, Marko; Ellis, Steven R; Fulco, Charles P; Engreitz, Jesse M; Schütz, Sabina; Lian, John; Gripp, Karen W; Weinberg, Olga K; Pinkus, Geraldine S; Gehrke, Lee; Regev, Aviv; Lander, Eric S; Gazda, Hanna T; Lee, Winston Y; Panse, Vikram G; Carr, Steven A; Sankaran, Vijay G

2018-03-22

Blood cell formation is classically thought to occur through a hierarchical differentiation process, although recent studies have shown that lineage commitment may occur earlier in hematopoietic stem and progenitor cells (HSPCs). The relevance to human blood diseases and the underlying regulation of these refined models remain poorly understood. By studying a genetic blood disorder, Diamond-Blackfan anemia (DBA), where the majority of mutations affect ribosomal proteins and the erythroid lineage is selectively perturbed, we are able to gain mechanistic insight into how lineage commitment is programmed normally and disrupted in disease. We show that in DBA, the pool of available ribosomes is limited, while ribosome composition remains constant. Surprisingly, this global reduction in ribosome levels more profoundly alters translation of a select subset of transcripts. We show how the reduced translation of select transcripts in HSPCs can impair erythroid lineage commitment, illuminating a regulatory role for ribosome levels in cellular differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced hypophosphatemic osteomalacia.

PubMed

Bhadada, Sanjay K; Palnitkar, Saroj; Qiu, Shijing; Parikh, Nayana; Talpos, Gary B; Rao, Sudhaker D

2013-11-01

Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.

Impaired face detection may explain some but not all cases of developmental prosopagnosia.

PubMed

Dalrymple, Kirsten A; Duchaine, Brad

2016-05-01

Developmental prosopagnosia (DP) is defined by severe face recognition difficulties due to the failure to develop the visual mechanisms for processing faces. The two-process theory of face recognition (Morton & Johnson, 1991) implies that DP could result from a failure of an innate face detection system; this failure could prevent an individual from then tuning higher-level processes for face recognition (Johnson, 2005). Work with adults indicates that some individuals with DP have normal face detection whereas others are impaired. However, face detection has not been addressed in children with DP, even though their results may be especially informative because they have had less opportunity to develop strategies that could mask detection deficits. We tested the face detection abilities of seven children with DP. Four were impaired at face detection to some degree (i.e. abnormally slow, or failed to find faces) while the remaining three children had normal face detection. Hence, the cases with impaired detection are consistent with the two-process account suggesting that DP could result from a failure of face detection. However, the cases with normal detection implicate a higher-level origin. The dissociation between normal face detection and impaired identity perception also indicates that these abilities depend on different neurocognitive processes. © 2015 John Wiley & Sons Ltd.

Improvement in social function and health-related quality of life after shunt surgery for idiopathic normal-pressure hydrocephalus.

PubMed

Petersen, Jakob; Hellström, Per; Wikkelsø, Carsten; Lundgren-Nilsson, Asa

2014-10-01

To investigate the impact of shunt surgery on the activity, participation, autonomy, and health-related quality of life (HRQOL) of patients with idiopathic normal-pressure hydrocephalus (iNPH) as well as the effect on caregiver burden. Thirty-seven patients (median age 70 years, range 50-89 years) with iNPH were evaluated before and 6 months after surgery. Symptoms and signs were assessed by the iNPH scale, activities of daily living (ADL) with the Functional Independence Measure (FIM) and Assessment of Motor and Process Skills (AMPS), autonomy and participation with Impact on Participation and Autonomy (IPA), and caregiver burden with the Caregiver Burden Scale (CBS). HRQOL was evaluated with the EQ-5D (EuroQol Group-5 Dimension health survey). Twenty-four patients (65%) improved clinically (iNPH scale score) and 31 (86%) improved their HRQOL after surgery, almost to the same level as found in the normal population. The patients became more independent in physical and cognitive activities, and participation and autonomy improved. The caregiver burden was decreased among caregivers to male patients but remained unchanged on the overall group level. After shunt surgery, patients with iNPH showed improvement in most aspects of social life, they became more independent, and their quality of life returned to nearly normal.

Respirator triggering of electron beam computed tomography (EBCT): evaluation of dynamic changes during mechanical expiration in the traumatized patient

NASA Astrophysics Data System (ADS)

Recheis, Wolfgang A.; Kleinsasser, Axel; Hatschenberger, Robert; Knapp, Rudolf; zur Nedden, Dieter; Hoermann, Christoph

1999-05-01

The purpose of this project is to evaluate the dynamic changes during expiration at different levels of positive end- expiratory pressure (PEEP) in the ventilated patient. We wanted to discriminate between normal lung function and acute respiratory distress syndrome (ARDS). After approval by the local Ethic Committee we studied two ventilated patients: (1) with normal lung function; (2) ARDS). We used the 50 ms scan mode of the EBCT. The beam was positioned 1 cm above the diaphragm. The table position remained unchanged. An electronic trigger was developed, that utilizes the respirators synchronizing signal to start the EBCT at the onset of expiration. During controlled mechanical expiration at two levels of PEEP (0 and 15 cm H2O), pulmonary aeration was rated as: well-aerated (-900HU/-500HU), poorly- aerated (-500HU/-100HU) and non-aerated (-100HU/+100HU). Pathological and normal lung function showed different dynamic changes (FIG.4-12). The different PEEP levels resulted in a significant change of pulmonary aeration in the same patient. Although we studied only a very limited number of patients, respirator triggered EBCT may be accurate in discriminating pathological changes due to the abnormal lung function in the mechanically ventilated patient.

Plasma testosterone levels in Alzheimer and Parkinson diseases.

PubMed

Okun, M S; DeLong, M R; Hanfelt, J; Gearing, M; Levey, A

2004-02-10

Testosterone deficiency, a treatable condition commonly seen in aging men, has been linked to Parkinson disease (PD) and Alzheimer disease (AD). In normal subjects, low testosterone levels are associated with cognitive and neuropsychiatric symptoms, yet the relationship between testosterone levels and cognitive function in PD and AD remains unclear. To examine the relationship of testosterone levels to age and cognitive function in PD and AD. Plasma testosterone levels were determined in men enrolled in a clinical registry of subjects with PD and AD, and neuropsychological testing was performed on subjects who consented. Testosterone levels in men with PD were compared with those in men with AD. In both groups, the relationship between testosterone levels and neuropsychological test scores was analyzed, adjusting for age and education. Linear regression analysis revealed that testosterone levels decreased with age in male PD patients (p < 0.03) and male AD patients (p < 0.07). The rate of decline was similar for the two groups. In PD patients, lower testosterone levels were associated with poorer performance on Trails B Seconds (p < 0.02). There is a similar age-related decline in plasma testosterone levels in men with either PD or AD. Previously described associations between low testosterone levels and frontal lobe dysfunction in normal aged men, together with these results, suggest that the hormonal deficiency may act as a "second hit" to impair cognitive function in neurodegenerative disease.

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

Hu, Zhi; Huang, Ge; Sadanandam, Anguraj

Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growthmore » and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels. Knock down of HJURP in human breast cancer cells using shRNA reduced the sensitivity to radiation treatment. HJURP mRNA levels were significantly correlated with CENPA mRNA levels. Conclusions: HJURP mRNA level is a prognostic factor for disease-free and overall survival in patients with breast cancer and is a predictive biomarker for sensitivity to radiotherapy.« less

CNS germinoma with elevated serum human chorionic gonadotropin level: Clinical characteristics and treatment outcome

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

Ogino, Hiroyuki; Shibamoto, Yuta; Takanaka, Tsuyoshi

2005-07-01

Purpose: The prognostic significance of human chorionic gonadotropin (HCG) level in central nervous system germinoma remains controversial. The purpose of this study was to compare clinical characteristics and prognosis of germinoma patients with normal and high HCG titers in the serum. Methods and Materials: We undertook a multi-institutional retrospective analysis of 103 patients with central nervous system germinoma whose serum HCG and/or {beta}-HCG level had been measured before treatment between 1984 and 2002. All patients had been treated with radiation therapy either alone (n = 66) or in combination with chemotherapy (n = 37) with a median dose of 47.8more » Gy. Results: HCG and/or {beta}-HCG level in the serum was high in 39% of all patients. The proportion of HCG-producing tumors was higher in the lesions at the basal ganglia than in the lesions at the other sites. No correlation was found between tumor size and HCG level, but there seemed to be a weak correlation between size and {beta}-HCG. The 5- and 10-year survival rates were 96% and 94%, respectively, in both patient groups with normal and high HCG (p = 0.99). The 5- and 10-year relapse-free survival rates were 87% and 82%, respectively, in patients with normal HCG level and were both 87% in patients with high HCG (p = 0.74). Also, no other patient-, tumor-, or treatment-related factors seemed to influence the prognosis of the patients. Conclusion: Serum HCG level does not seem to influence patient prognosis when treated with sufficient doses of radiation. Relationship between tumor size and site and HCG level should be investigated further.« less

Comparison of serum vaspin levels and vaspin expression in adipose tissue and smooth muscle tissue in pregnant women with and without gestational diabetes.

PubMed

Tang, Yuping; Qiao, Ping; Qu, Xiaoxian; Bao, Yirong; Li, Yuhong; Liao, Yini; Ying, Hao

2017-10-01

Vaspin is associated with metabolic parameters and insulin resistance. However, the expression of vaspin in visceral adipose tissue (VAT) in pregnant women with gestational diabetes mellitus (GDM) has not been fully explored, and the contribution of vaspin to the biological mechanisms underlying GDM remains unclear. This study aimed to compare circulating vaspin levels and its expression in different insulin target tissues including subcutaneous adipose tissue (SAT), VAT and smooth muscle tissue (SMT) in pregnant women with and without GDM. A total of 37 women with GDM (GDM group) and 37 normal pregnant women (control group) were selected. Fasting plasma glucose (FPG), fasting insulin (FINS) and serum vaspin levels were quantified at term, and homeostasis model of assessment2-insulin resistance (HOMA2-IR) values were calculated. RT-qPCR and Western blotting were used to measure mRNA and protein levels of vaspin in VAT, SAT and SMT of 15 GDM women and normal pregnant women. In the GDM group, serum vaspin concentrations were significantly higher than in the control group. Serum vaspin levels were positively correlated with HOMA2-IR in the GDM group but not in the control group. In the GDM group, vaspin mRNA and protein expression levels in SAT and VAT were both significantly higher than in controls, but no difference was found in SMT. Moreover, relative mRNA but not protein expression levels of vaspin in SAT were highest among the three tissues in both groups. Circulating vaspin levels and expression of vaspin in SAT and VAT were higher in GDM women than in normal pregnant women. However, the specific role of vaspin from SAT and VAT in the pathogenesis of GDM needs further study. © 2017 John Wiley & Sons Ltd.

Transformation of a MGUS to overt multiple myeloma: the possible role of a pituitary macroadenoma secreting high levels of insulin-like growth factor 1 (IGF-1).

PubMed

Tucci, Alessandra; Bonadonna, Stefania; Cattaneo, Chiara; Ungari, Marco; Giustina, Andrea; Guiseppe, Rossi

2003-03-01

We present a female patient with monoclonal gammopathy of undetermined significance who has remained stable for five years but evolved to overt myeloma in strict temporal relationship with the diagnosis of GH-secreting pituitary macroadenoma. IGF-I serum levels correlated with serum and urine M component. Since the in vitro role of IGF-I on proliferation and survival of normal and neoplastic plasma cells has been recently emphasized, the pathogenetic link between acromegaly and transformation of gammopathy to overt myeloma in this case is discussed.

CA 15-3 predicting breast cancer relapse: beware of vitamin B12 deficiency.

PubMed

Rassy, Elie El; Ghor, Maya Al; Kattan, Joseph

2018-05-10

A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.

Susceptibility weighted imaging of stroke brain in response to normobaric oxygen (NBO) therapy

NASA Astrophysics Data System (ADS)

Zhou, Iris Y.; Igarashi, Takahiro; Guo, Yingkun; Sun, Phillip Z.

2015-03-01

The neuroprotective effect of oxygen leads to recent interest in normobaric oxygen (NBO) therapy after acute ischemic stroke. However, the mechanism remains unclear and inconsistent outcomes were reported in human studies. Because NBO aims to improve brain tissue oxygenation by enhancing oxygen delivery to ischemic tissue, monitoring the oxygenation level changes in response to NBO becomes necessary to elucidate the mechanism and to assess the efficacy. Susceptibility weighted imaging (SWI) which provides a new MRI contrast by combining the magnitude and phase images is fit for purpose. SWI is sensitive to deoxyhemoglobin level changes and thus can be used to evaluate the cerebral metabolic rate of oxygen. In this study, SWI was used for in vivo monitoring of oxygenation changes in a rat model of permanent middle cerebral artery occlusion (MCAO) before, during and after 30 min of NBO treatment. Regions of interest in ischemic core, penumbra and contralateral normal area were generated based on diffusionweighted imaging and perfusion imaging. Significant differences in SWI indicating different oxygenation levels were generally found: contralateral normal > penumbra > ischemic core. Ischemic core showed insignificant increase in oxygenation during NBO and returned to pre-treatment level after termination of NBO. Meanwhile, the oxygenation levels slightly increased in contralateral normal and penumbra regions during NBO and significantly decreased to a level lower than pre-treatment after termination of NBO, indicating secondary metabolic disruption upon the termination of transient metabolic support from oxygen. Further investigation of NBO effect combined with reperfusion is necessary while SWI can be used to detect hemorrhagic transformation after reperfusion.

Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function.

PubMed

Pang, S; Levine, L S; Stoner, E; Opitz, J M; Pollack, M S; Dupont, B; New, M I

1983-04-01

In studies of a 6-yr-old boy and his non-HLA identical 8-yr-old sister, we demonstrated 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency in the biosynthetic pathways of glucocorticoids and androgens, but not mineralocorticoids. The sister did not manifest abnormal genital development at birth, but developed premature adrenarche at the age of 4 yr, with clitoromegaly and advanced bone age. The brother had perineal hypospadias at birth and developed premature adrenarche at the age of 6 yr. In both siblings, baseline and ACTH-stimulated delta 5 steroids were markedly elevated. The baseline and ACTH-stimulated ratios of delta 5 to delta 4 steroids remained extremely high, and all steroids promptly suppressed with dexamethasone (DEX). Normal baseline PRA and serum and urinary aldosterone (Aldo) levels increased after stimulation with a low Na+ diet. Renal Na+ conservation was normal after dietary Na+ deprivation with and without DEX administration. The PRA to pH 1 Aldo ratio remained normal with normal and low Na+ diets, regardless of DEX administration, indicating normal glomerulosa function with renin stimulation. In both siblings, ACTH increased PRA and Aldo levels, maintaining the PRA to pH 1 Aldo ratio unchanged from the baseline value. In contrast, in control children, PRA was suppressed, while Aldo increased, resulting in a fall of the PRA to pH 1 Aldo ratio. The increase in PRA with exogenous ACTH in these siblings suggests there may be an ACTH-stimulable mineralocorticoid antagonist. During prolonged DEX administration, hCG administration caused a slight increase in 17-hydroxypregnenolone and dehydroepiandrosterone in both the siblings, while testosterone (T) rose poorly in the brother, and estradiol did not rise at all in the sister. These results suggest the possibility of a deficiency of 3 beta-HSD in the gonads as well as the adrenals. After [3H]dehydroepiandrosterone iv infusion, there was normal conversion to [3H]-conjugated testosterone glucuronide, suggesting the presence of normal peripheral 3 beta-HSD activity. We propose that in these siblings, there is a deficiency of 3 beta-HSD in the adrenal zona fasciculata and zona reticularis, whereas 3 beta-HSD activity is intact in the zona glomerulosa. In addition, in these siblings, 3 beta-HSD deficiency was present in the gonads, while peripheral 3 beta-HSD activity appeared to be intact. These cases demonstrate further the heterogeneity of congenital adrenal hyperplasia due to 3 beta-HSD deficiency.

[Addison disease during pregnancy--a diagnostic dilemma. Symptoms are similar to normal pregnancy problems].

PubMed

Wålinder, Olov

The symptoms of primary adrenocortical insufficiency (Addison's disease) such as fatigue, anorexia, hypotension and hyperpigmentation are similar to those of normal pregnancy. Addison's disease is rare and the diagnosis can easily be overlooked during pregnancy. The concentration of corticosteroid-binding globulin (CBG) and cortisol in serum as well as urinary free cortisol increase 2-3 times during pregnancy. Therefore, the reference ranges for nonpregnant persons cannot be used during pregnancy. The diagnosis of Addison's disease in pregnancy should be based on analysis of p-ACTH which remains within the reference range in normal pregnancy until delivery. A case of Addison's disease diagnosed during pregnancy is presented and it illustrates the diagnostic difficulties. In patients taking oral estrogen containing contraceptives, serum levels of CBG and cortisol also increase 2-3 times, making s-cortisol values difficult to interpret. Also in these patients, analysis of p-ACTH is of value when suspecting Addison's disease.

Fructose 2,6-bisphosphate and 6-phosphofructo-2-kinase during liver regeneration.

PubMed Central

Rosa, J L; Ventura, F; Carreras, J; Bartrons, R

1990-01-01

Glycogen and fructose 2,6-bisphosphate levels in rat liver decreased quickly after partial hepatectomy. After 7 days the glycogen level was normalized and fructose 2,6-bisphosphate concentration still remained low. The 'active' (non-phosphorylated) form of 6-phosphofructo-2-kinase varied in parallel with fructose 2,6-bisphosphate levels, whereas the 'total' activity of the enzyme decreased only after 24 h, similarly to glucokinase. The response of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from hepatectomized rats (96 h) to sn-glycerol 3-phosphate and to cyclic AMP-dependent protein kinase was different from that of the enzyme from control animals and similar to that of the foetal isoenzyme. PMID:2173548

The Relationship between the Behavioral Hearing Thresholds and Maximum Bilirubin Levels at Birth in Children with a History of Neonatal Hyperbilirubinemia

PubMed Central

Panahi, Rasool; Jafari, Zahra; Sheibanizade, Abdoreza; Salehi, Masoud; Esteghamati, Abdoreza; Hasani, Sara

2013-01-01

Introduction: Neonatal hyperbilirubinemia is one of the most important factors affecting the auditory system and can cause sensorineural hearing loss. This study investigated the relationship between behavioral hearing thresholds in children with a history of jaundice and the maximum level of bilirubin concentration in the blood. Materials and Methods: This study was performed on 18 children with a mean age of 5.6 years and with a history of neonatal hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and brainstem evoked responses were evaluated in all children. Results: Six children (33.3%) had normal hearing thresholds and the remaining (66.7%) had some degree of hearing loss. There was no significant relationship (r=-0.28, P=0.09) between the mean total bilirubin levels and behavioral hearing thresholds in all samples. A transient evoked emission was seen only in children with normal hearing thresholds however in eight cases brainstem evoked responses had not detected. Conclusion: Increased blood levels of bilirubin at the neonatal period were potentially one of the causes of hearing loss. There was a lack of a direct relationship between neonatal bilirubin levels and the average hearing thresholds which emphasizes on the necessity of monitoring the various amounts of bilirubin levels. PMID:24303432

Stimulatory effect of clebopride on human prolactin secretion.

PubMed

Perez-Lopez, F R; Legido, A; Sisskin, M; Abos, M D

1980-11-01

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Induction of plasma acetylcholinesterase activity in mice challenged with organophosphorus poisons

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

Duysen, Ellen G.; Lockridge, Oksana, E-mail: olockrid@unmc.edu

2011-09-01

The restoration of plasma acetylcholinesterase activity in mice following inhibition by organophosphorus pesticides and nerve agents has been attributed to synthesis of new enzyme. It is generally assumed that activity levels return to normal, are stable and do not exceed the normal level. We have observed over the past 10 years that recovery of acetylcholinesterase activity levels in mice treated with organophosphorus agents (OP) exceeds pretreatment levels and remains elevated for up to 2 months. The most dramatic case was in mice treated with tri-cresyl phosphate and tri-ortho-cresyl phosphate, where plasma acetylcholinesterase activity rebounded to a level 250% higher thanmore » the pretreatment activity. The present report summarizes our observations on plasma acetylcholinesterase activity in mice treated with chlorpyrifos, chlorpyrifos oxon, diazinon, tri-ortho-cresyl phosphate, tri-cresyl phosphate, tabun thiocholine, parathion, dichlorvos, and diisopropylfluorophosphate. We have developed a hypothesis to explain the excess acetylcholinesterase activity, based on published observations. We hypothesize that acetylcholinesterase activity is induced when cells undergo apoptosis and that consequently there is a rise in the level of plasma acetylcholinesterase. - Highlights: > Acetylcholinesterase activity is induced by organophosphorus agents. > AChE induction is related to apoptosis. > Induction of AChE activity by OP is independent of BChE.« less

Normocalcemia without hyperparathyroidism in vitamin D-deficient rats.

PubMed

Kollenkirchen, U; Fox, J; Walters, M R

1991-03-01

Despite numerous attempts, no reliable dietary regimen exists to achieve vitamin D deficiency (-D) in rats without attendant changes in plasma parathyroid hormone (PTH), Ca, or phosphate. This represents an important obstacle to proper investigations of the physiologic role(s) of vitamin D metabolites in the function of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] target tissues. This paper describes the successful development of such a diet, which uses a combination of high Ca content, properly controlled Ca/P ratio, and lactose. Normal weanling rats were fed diets containing A, 0.8% Ca, 0.5% P, +D3, or -D diets containing B, 0.8% Ca and 0.5% P; C, 2.0% Ca and 1.25% P; or D, 2.0% Ca, 1.25% P, and 20% lactose. After 6 diet weeks group D rats remained normocalcemic and normophosphatemic, but diet groups B and C became hypocalcemic (6.9 +/- 0.8 and 7.2 +/- 0.4 mg/dl, respectively). Thus high dietary Ca and P was incapable of maintaining normal plasma Ca levels in the absence of dietary lactose. The normocalcemia in group D was not maintained by elevated PTH secretion because N-terminal PTH levels were also normal (14 +/- 3 versus 20 +/- 5 pg/ml). In contrast, PTH levels were markedly elevated in hypocalcemic groups B and C (47 +/- 7 and 48 +/- 10 pg/ml, respectively). Plasma 25-OHD3 and 1,25-(OH)2D3 levels were reduced to less than 120 and less than 12 pg/ml, respectively, in all -D groups. Thus the high-Ca diet and the use of normal weanlings did not impede the development of vitamin D deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.

PubMed

Phondeechareon, Tanapol; Wattanapanitch, Methichit; U-Pratya, Yaowalak; Damkham, Chanapa; Klincumhom, Nuttha; Lorthongpanich, Chanchao; Kheolamai, Pakpoom; Laowtammathron, Chuti; Issaragrisil, Surapol

2016-10-01

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients.

Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia.

PubMed

Carlsson, Göran; Wahlin, Ylva-Britt; Johansson, Anders; Olsson, Anders; Eriksson, Torbjörn; Claesson, Rolf; Hänström, Lennart; Henter, Jan-Inge

2006-04-01

Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.

The overall computer/mobile devices usage time is related to newly diagnosed non-alcoholic fatty liver disease: a population-based study.

PubMed

Meng, Ge; Liu, Fangfang; Fang, Liyun; Li, Chunlei; Zhang, Qing; Liu, Li; Wu, Hongmei; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Bao, Xue; Su, Qian; Gu, Yeqing; Yu, Fei; Yang, Huijun; Yu, Bin; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Guo, Qi; Chen, Xin; Song, Kun; Wang, Guolin; Huang, Guowei; Niu, Kaijun

2016-11-01

The computer/mobile devices usage time (CMD-UT) is closely related to a sedentary lifestyle, which is an important risk factor for non-alcoholic fatty liver disease (NAFLD). But their direct relationship remains unclear. We aimed to examine the relationship between CMD-UT and newly diagnosed non-alcoholic fatty liver disease (NAFLD) in Chinese adults. This cross-sectional study was conducted on 7516 adults in Tianjin, China. The CMD-UT was collected via a questionnaire included five categories. NAFLD [with normal or elevated alanine transaminase (ALT) levels] was diagnosed by at least twice liver ultrasonography examinations and serum ALT concentrations (>41 U/L in males and >33 U/L in females). The prevalence of overall NAFLD, NAFLD with normal or elevated ALT levels was 18.2, 14.2, and 4.0%, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence interval) of having overall NAFLD by increasing CMD-UT levels were 1.00 for <1 h/d, 1.58 (1.22-2.05) for 1-3 h/d, 1.58 (1.18-2.11) for 3-5 h/d, 1.65 (1.21-2.27) for 5-10 h/d, and 1.99 (1.29-3.05) for ≥10h/d (P-trend for CMD-UT levels = 0.02), respectively. Similar relations were observed with the use of NAFLD with normal or elevated ALT levels. The present study is the first to find that CMD-UT levels are independently associated with NAFLD. Key Messages The computer/mobile devices usage time levels are independently associated with the prevalence of non-alcoholic fatty liver disease.

Kinetochore localized Mad2 and Cdc20 is itself insufficient for triggering the mitotic checkpoint when Mps1 is low in Drosophila melanogaster neuroblasts.

PubMed

Herriott, Ashleigh; Sweeney, Michele; Whitaker, Michael; Taggart, Michael; Huang, Jun-Yong

2012-12-15

The relationships between the kinetochore and checkpoint control remain unresolved. Here, we report the characterization of the in vivo behavior of Cdc20 and Mad2 and the relevant spindle assembly checkpoint (SAC) functions in the neuroblasts of a Drosophila Mps1 weak allele (ald (B4-2) ). ald (B4-2) third instar larvae brain samples contain only around 16% endogenous Mps1 protein, and the SAC function is abolished. However, this does not lead to rapid anaphase onset and mitotic exit, in contrast to the loss of Mad2 alone in a mad2 (EY) mutant. The level of GFP-Cdc20 recruitment to the kinetochore is unaffected in ald (B4-2) neuroblasts, while the level of GFP-Mad2 is reduced to just about 20%. Cdc20 and Mad2 display only monophasic exponential kinetics at the kinetochores. The ald (B4-2) heterozygotes expressed approximately 65% of normal Mps1 protein levels, and this is enough to restore the SAC function. The kinetochore recruitment of GFP-Mad2 in response to SAC activation increases by around 80% in heterozygotes, compared with just about 20% in ald (B4-2) mutant. This suggests a correlation between Mps1 levels and Mad2 kinetochore localization and perhaps the existence of a threshold level at which Mps1 is fully functional. The failure to arrest the mitotic progression in ald (B4-2) neuroblasts in response to colchicine treatment suggests that when Mps1 levels are low, approximately 20% of normal GFP-Mad2, alongside normal levels of GFP-Cdc20 kinetochore recruitments, is insufficient for triggering SAC signal propagation.

Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

PubMed

De Bellis, Annamaria; Bellastella, Giuseppe; Falorni, Alberto; Aitella, Ernesto; Barrasso, Mariluce; Maiorino, Maria Ida; Bizzarro, Elio; Bellastella, Antonio; Giugliano, Dario; Esposito, Katherine

2017-10-01

Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages. © 2017 European Society of Endocrinology.

Impact of CPAP treatment on cardiac biomarkers and pro-BNP in obstructive sleep apnea syndrome.

PubMed

Cifçi, Nilüfer; Uyar, Meral; Elbek, Osman; Süyür, Hüseyin; Ekinci, Erhan

2010-09-01

To evaluate the effect of continuous positive airway pressure (CPAP) therapy on pro-brain natriuretic peptide (BNP) and cardiac markers in patients with obstructive sleep apnea syndrome and normal cardiac function. Thirty-three consecutive patients with sleep apnea syndrome were analysed for serum pro-BNP and cardiac markers prior to and after 6 months of CPAP therapy. Twenty five patients had normal (83.3%) while remaining five (16.7%) revealed high pro-BNP values. We did not detect any significant difference between severity of obstructive sleep apnea syndrome and serum pro-BNP levels (p = 0.534). A statistically significant difference was not observed between basal and sixth-month creatine kinase (CK), creatine kinase-MB (CK-MB), troponin I, pro-BNP, aspartate transaminase (AST), and CK levels in patients with sleep apnea syndrome (p > 0.05). Obstructive sleep apnea syndrome does not induce myocardial damage enough to increase serum pro-BNP, CK, CK-MB, troponin I, and AST levels. Markers sensitive to ischemia could be preferred to evaluate effect of obstructive sleep apnea syndrome.

Levetiracetam Reverses Synaptic Deficits Produced by Overexpression of SV2A

PubMed Central

Yao, Jia; Bleckert, Adam; Hill, Jessica; Bajjalieh, Sandra M.

2011-01-01

Levetiracetam is an FDA-approved drug used to treat epilepsy and other disorders of the nervous system. Although it is known that levetiracetam binds the synaptic vesicle protein SV2A, how drug binding affects synaptic functioning remains unknown. Here we report that levetiracetam reverses the effects of excess SV2A in autaptic hippocampal neurons. Expression of an SV2A-EGFP fusion protein produced a ∼1.5-fold increase in synaptic levels of SV2, and resulted in reduced synaptic release probability. The overexpression phenotype parallels that seen in neurons from SV2 knockout mice, which experience severe seizures. Overexpression of SV2A also increased synaptic levels of the calcium-sensor protein synaptotagmin, an SV2-binding protein whose stability and trafficking are regulated by SV2. Treatment with levetiracetam rescued normal neurotransmission and restored normal levels of SV2 and synaptotagmin at the synapse. These results indicate that changes in SV2 expression in either direction impact neurotransmission, and suggest that levetiracetam may modulate SV2 protein interactions. PMID:22220214

Assessment of gender-related differences in vitamin D levels and cardiovascular risk factors in Saudi patients with type 2 diabetes mellitus.

PubMed

Abudawood, Manal; Tabassum, Hajera; Ansar, Sabah; Almosa, Khalid; Sobki, Samia; Ali, Mir Naiman; Aljohi, Ali

2018-01-01

Diabetes is a major risk factor for cardiovascular disease (CVD) including stroke, coronary heart disease, and peripheral artery disease. It remains a leading cause of mortality throughout the world, affecting both women and men. This investigation was aimed to study gender based differences in cardiovascular risk factors of adult population with type-2 diabetes mellitus (T2DM) and to check the correlation between serum HbA1C, lipid profile and serum vitamin D levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross-sectional study involving subjects was divided into two gender based groups; normal male (800), diabetic male (800) and normal female (800) and T2DM females (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)-vitamin D in all groups. All the glycemic control parameters and lipid profile parameters were found to be significantly different in diabetic vs non-diabetic group (p < 0.001) in both genders. The results also show that vitamin D concentration decreased significantly (p < 0.001) in diabetic patients than the healthy individuals in both the genders. Vitamin-D and HbA1C were negatively correlated in both males and females in T2DM patients and significant at P < 0.05. Our study reveals that dyslipidemia remains one of the major risk factors of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.

Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy.

PubMed

Gozal, David; Kheirandish-Gozal, Leila; Serpero, Laura D; Sans Capdevila, Oscar; Dayyat, Ehab

2007-11-13

Obstructive sleep apnea (OSA) in children is associated with cardiovascular morbidity such as systemic and pulmonary hypertension. However, it remains unclear whether endothelial dysfunction occurs in pediatric OSA and whether it is reversible on effective treatment of OSA. Consecutive nonobese children (aged 6 to 11 years) who were diagnosed with OSA after overnight polysomnography and control children matched on the basis of age, gender, ethnicity, and body mass index underwent blood draw the next morning for soluble CD40 ligand, asymmetric dimethylarginine (ADMA), and nitrotyrosine levels, as well as 2 iterations of 60-second cuff-occlusion tests for assessment of endothelial function. These tests were repeated 4 to 6 months after adenotonsillectomy. OSA children showed blunted reperfusion kinetics after release of occlusion, which completely normalized in 20 of 26 patients after adenotonsillectomy. All 6 children in whom no improvements occurred had a strong family history of cardiovascular disease (versus 2 of the remaining 20 patients; P<0.04). Plasma nitrotyrosine and ADMA levels were similar in OSA and control children; however, soluble CD40 ligand levels were higher in OSA children and were reduced after treatment, particularly in those with normalized hyperemic responses. Postocclusive hyperemia is consistently blunted in children with OSA, and such altered endothelial function is reversible 4 to 6 months after treatment, particularly if a family history of cardiovascular disease is not present. Although no evidence for either nitric oxide-dependent oxidative/nitrosative stress or for the increased presence of the circulating nitric oxide synthase inhibitor ADMA was found in children with OSA, soluble CD40 ligand levels were increased in OSA and reflected the changes in endothelial function after treatment.

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues.

PubMed

Van Herck, Stijn L J; Geysens, Stijn; Bald, Edward; Chwatko, Grazyna; Delezie, Evelyne; Dianati, Elham; Ahmed, R G; Darras, Veerle M

2013-07-01

Methimazole (MMI) is an anti-thyroid drug used in the treatment of chronic hyperthyroidism. There is, however, some debate about its use during pregnancy as MMI is known to cross the mammalian placenta and reach the developing foetus. A similar problem occurs in birds, where MMI is deposited in the egg and taken up by the developing embryo. To investigate whether maternally derived MMI can have detrimental effects on embryonic development, we treated laying hens with MMI (0.03% in drinking water) and measured total and reduced MMI contents in the tissues of hens and embryos at different stages of development. In hens, MMI was selectively increased in the thyroid gland, while its levels in the liver and especially brain remained relatively low. Long-term MMI treatment induced a pronounced goitre with a decrease in thyroxine (T₄) content but an increase in thyroidal 3,5,3'-triiodothyronine (T₃) content. This resulted in normal T₃ levels in tissues except in the brain. In chicken embryos, MMI levels were similar in the liver and brain. They gradually decreased during development but always remained above those in the corresponding maternal tissues. Contrary to the situation in hens, T₄ availability was only moderately affected in embryos. Peripheral T₃ levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T₃ content was decreased at all embryonic stages tested. We conclude that all embryonic tissues are exposed to relatively high doses of MMI and its oxidised metabolites. The effect of maternal MMI treatment on embryonic thyroid hormone availability is most pronounced for brain T₃ content, which is reduced throughout the embryonic development period.

Detailed characterization of a long-term rodent model of critical illness and recovery.

PubMed

Hill, Neil E; Saeed, Saima; Phadke, Rahul; Ellis, Matthew J; Chambers, Darren; Wilson, Duncan R; Castells, Josiane; Morel, Jerome; Freysennet, Damien G; Brett, Stephen J; Murphy, Kevin G; Singer, Mervyn

2015-03-01

To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic, and muscle function. Randomized controlled animal study. University research laboratory. Male Wistar rats. Intraperitoneal injection of the fungal cell wall constituent, zymosan or n-saline. Following intervention, rats were followed for up to 2 weeks. Animals with zymosan peritonitis reached a clinical and biochemical nadir on day 2. Initial reductions were seen in body weight, total body protein and fat, and muscle mass. Leg muscle fiber diameter remained subnormal at 14 days with evidence of persisting myonecrosis, even though gene expression of regulators of muscle mass (e.g., MAFbx, MURF1, and myostatin) had peaked on days 2-4 but normalized by day 7. Treadmill exercise capacity, forelimb grip strength, and in vivo maximum tetanic force were also reduced. Food intake was minimal until day 4 but increased thereafter. This did not relate to appetite hormone levels with early (6 hr) rises in plasma insulin and leptin followed by persisting subnormal levels; ghrelin levels did not change. Serum interleukin-6 level peaked at 6 hours but had normalized by day 2, whereas interleukin-10 remained persistently elevated and high-density lipoprotein cholesterol persistently depressed. There was an early myocardial depression and rise in core temperature, yet reduced oxygen consumption and respiratory exchange ratio with a loss of diurnal rhythmicity that showed a gradual but incomplete recovery by day 7. This detailed physiological, metabolic, hormonal, functional, and histological muscle characterization of a model of critical illness and recovery reproduces many of the findings reported in human critical illness. It can be used to assess putative therapies that may attenuate loss, or enhance recovery, of muscle mass and function.

The Natural History of Subclinical Hyperthyroidism in Graves' Disease: The Rule of Thirds.

PubMed

Zhyzhneuskaya, Sviatlana; Addison, Caroline; Tsatlidis, Vasileios; Weaver, Jolanta U; Razvi, Salman

2016-06-01

There is little information regarding the natural history of subclinical hyperthyroidism (SH) due to Graves' disease (GD). A prospective analysis was conducted of patients with SH due to GD between 2007 and 2013 with at least 12 months of follow-up. SH was diagnosed if serum thyrotropin (TSH) was below the laboratory reference range (0.4-4.0 mIU/L) and when thyroid hormones were normal. GD was confirmed by either a raised TSH receptor antibody (TRAb) level or uniform uptake on Technetium scan. Forty-four patients (89% female, 16% current smokers, and 5% with active Graves' orbitopathy) were diagnosed with SH due to GD. Over the follow-up period (median 32 months), approximately one third (34%) of the cohort progressed to overt hyperthyroidism, one third (34%) normalized their thyroid function, slightly less than one third (30%) remained in the SH state, while one person became hypothyroid. Multivariate regression analysis showed that older age and positive antithyroid peroxidase (TPO) antibody status had a positive association with risk of progression to overt hyperthyroidism, with hazard ratios of 1.06 ([confidence interval (CI) 1.02-1.10], p < 0.01) per year and 10.15 ([CI 1.83-56.23], p < 0.01), respectively, independent of other risk factors including, smoking, TRAb levels at diagnosis, and sex. A third each of patients with SH due to GD progress, normalize, or remain in the SH state. Older people and those with positive anti-TPO antibodies have a higher risk of progression of the disease. These novel data need to be verified and confirmed in larger cohorts and over longer periods of follow-up.

Normalization of Elevated Tumor Marker CA27-29 after Bilateral Lung Transplantation in a patient with Breast Cancer and Idiopathic Pulmonary Fibrosis.

PubMed

Copur, Mehmet Sitki; Wurdeman, Julie Marie; Nelson, Debra; Ramaekers, Ryan; Gauchan, Dron; Crockett, David

2017-12-11

Solid tumors involving glandular organs express mucin glycoprotein which is eventually shed into the circulation. As aresult these proteins can easily be measured in the serum and be used as potential tumor markers. The most commonly used tumor markers for breast cancer are CA 27-29 and CA 15-3, which both measure the glycoprotein product of the mucin-1 (MUC1) gene. CA 27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in breast cancer patients. Most oncology clinical practice guidelines do not recommend the use of tumor markers for routine surveillance of early stage disease but recognize their utility in the metastatic setting. Herein, we present a patient with stage III-A breast cancer and pre-existing hypersensitivity pneumonitis who is found to have an elevated serum tumor marker CA 27-29. After successful curative intent treatment of her early stage breast cancer, she developed gradual and progressive worsening of her lung disease with eventual development of severe pulmonary fibrosis requiring bilateral lung transplantation. As part of the pre-transplant evaluation, she was found to have an elevation of serum tumor marker CA 27-29. While the diagnostic evaluation, including imaging studies was negative for the presence of recurrent disease, the serial serum tumor marker CA 27-29 levels remained persistently elevated. The decision was made for her to undergo bilateral lung transplantation. Shortly after surgery her CA27-29 tumor marker level returned to normal range, and it has continued to remain in the normal range with no evidence of breast cancer recurrence.

PRL-3 promotes breast cancer progression by downregulating p14ARF-mediated p53 expression.

PubMed

Xie, Hua; Wang, Hao

2018-03-01

Prior studies have demonstrated that phosphatase of regenerating liver-3 (PRL-3) serves avital function in cell proliferation and metastasis in breast cancer. However, the molecular mechanisms underlying the function of PRL-3 in breast cancer remain unknown. PRL-3 expression was analyzed in 24 pairs of breast cancer and normal tissues using the reverse transcription-quantitative polymerase chain reaction assay. The results of the present study identified that the expression of PLR-3 in breast cancer tissues was increased 4.2-fold, compared with normal tissues. Notably, overexpression of PRL-3 significantly promoted the proliferation of cancer cells and inhibited endogenous p53 expression by downregulating the expression level of p14 alternate reading frame (p14 ARF ). In addition, decreased expression levels of PRL-3 resulted in decreased breast cancer cell proliferation and increased expression level of p14 ARF . These results suggested that PRL-3 enhances cell proliferation by downregulating p14 ARF expression, which results in decreased levels ofp53. The results of the present study demonstrated that PRL-3 promotes tumor proliferation by affecting the p14 ARF -p53 axis, and that it may serve as a prognostic marker for patients with breast cancer.

Long-Term Prognosis of Patients with Esophageal Atresia and/or Tracheoesophageal Fistula.

PubMed

Bakal, Unal; Ersoz, Fikret; Eker, Irem; Sarac, Mehmet; Aydin, Mustafa; Kazez, Ahmet

2016-05-01

To investigate long-term prognosis of infants with esophageal atresia (EA) and/or tracheoesophageal fistula (TEF). The data of patients with EA were investigated from their medical files. For the neurodevelopmental evaluation, they were requested to come for a return visit to authors' polyclinic. Intellectual development was assessed by Ankara Developmental Screening Inventory (ADSI) (for 0-6 age) and Wechsler Intelligence Scale for Children-Revised (WISC-R) (for 6-16 age). Of the 57 patients, 50 had EA+ distal TEF (87.7 %), six had isolated EA (10.5 %) and one had isolated TEF (1.8 %). Of the total patients, 18 cases (31 %) died and remaining 39 cases (69 %) survived. In the surviving cases, the most common long-term complication was dysphagia (n = 37, 94.8 %). Intellectual levels of the 24 patients assessed by ADSI were normal and of the remaining 15 cases evaluated by WISC-R ranged between 95 and 110 points. The long-term complications and hospital visits are common in surviving cases of EA; however, they have normal cognitive functions and physical developmental characteristics.

Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum

PubMed Central

Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J.; Ingrand, Pierre; Hankard, Régis

2016-01-01

Introduction Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. Objective To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. Materials and Methods This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Results Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Conclusion Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period. PMID:28005966

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

PubMed Central

Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI. PMID:26474181

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

PubMed

Pogliaghi, Manuela; Ripa, Marco; Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5mg intravaginal prasterone for 12 weeks.

PubMed

Martel, Céline; Labrie, Fernand; Archer, David F; Ke, Yuyong; Gonthier, Renaud; Simard, Jean-Nicolas; Lavoie, Lyne; Vaillancourt, Mario; Montesino, Marlene; Balser, John; Moyneur, Érick

2016-05-01

This study integrates all data obtained in women aged 40-80years enrolled with moderate to severe symptoms of vulvovaginal atrophy (VVA) who received daily intravaginal administration of 0.50% (6.5mg) dehydroepiandrosterone (DHEA; prasterone) for 12weeks (n=723; ITT-S population) as compared with placebo (n=266; ITT-S population). To this end, serum steroid levels (DHEA, DHEA-sulfate (DHEA-S), androst-5-ene-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G)) were measured at Day 1 and Week 12 by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following validation performed according to the FDA guidelines [1-6]. In agreement with the mechanisms of intracrinology where DHEA is exclusively transformed intracellularly into active sex steroids which act and are inactivated locally before being released as glucuronided or sulfated metabolites for elimination by the kidneys and liver, all sex steroids remained well within normal postmenopausal values following administration of intravaginal DHEA. Serum estradiol, the most relevant sex steroid, was measured after 12weeks of treatment at 3.36pg/ml (cITT-S population) or 19% below the normal postmenopausal value of 4.17pg/ml. On the other hand, serum E1-S, the best recognized marker of global estrogenic activity, shows an average value of 209pg/ml at 12 weeks compared to 220pg/ml in normal postmenopausal women. Moreover, serum ADT-G, the main metabolite of androgens, also remains well within normal postmenopausal values. The present data shows that a low daily intravaginal dose (6.5mg) of DHEA (prasterone) which is efficacious on the symptoms and signs of VVA, permits to achieve the desired local efficacy without systemic exposure, in agreement with the stringent mechanisms of menopause established after 500 million years of evolution where each cell in each tissue is the master of its sex steroid exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sperm DNA fragmentation in boars is delayed or abolished by using sperm extenders.

PubMed

Pérez-Llano, Begoña; Enciso, María; García-Casado, Pedro; Sala, Rubén; Gosálvez, Jaime

2006-12-01

The semen quality of seven young adult boars was assessed for percentages of sperm motility, normal acrosomes, abnormal sperm, cells positive to sHOST (short Hipoosmotic Swelling Test), HPNA cells (sHOST Positive with Normal Acrosome cells) and the percentage of sperm heads, which exhibited DNA fragmentation using the Sperm Chromatin Dispersion test (SCD). These parameters were analysed in sperm samples both undiluted and diluted using a commercial extender and stored at 15 degrees C for 21 days. Results showed that semen quality decreases faster in the undiluted semen samples from day 0 to day 7 compared to diluted semen samples that remained with a high quality up to day 11. The undiluted semen exhibited a low DNA fragmentation index (DFI) during the first days and then a significant increase from day 7 up to day 21. This increase in the DFI coincided with the lowest levels of the other semen quality parameters. On the contrary, the samples diluted in the commercial extender showed very low levels of DNA fragmentation in all boars during the preservation period. When the evolution of DNA fragmentation was analysed in the undiluted samples, differences were found among boars. These differences were not shown in the samples diluted in the extender where the basal DFI remained stable during the 21 days. The main conclusion of this study was that some sperm extenders delay or partially prevent sperm DNA fragmentation.

Long-Term Energy Deficit in Mice Causes Long-Lasting Hypothalamic Alterations after Recovery.

PubMed

Méquinion, Mathieu; Le Thuc, Ophélia; Zgheib, Sara; Alexandre, David; Chartrel, Nicolas; Rovère, Carole; Hardouin, Pierre; Viltart, Odile; Chauveau, Christophe

2017-01-01

Although the short-term effects of fasting or energy deficit on hypothalamic neuropeptide circuitries are now better understood, the effects of long-term energy deficit and refeeding remain to be elucidated. We showed that after a long-term energy deficit, mice exhibited persistent hypoleptinemia following the refeeding period despite restoration of fat mass, ovarian activity, and feeding behavior. We aimed to examine the hypothalamic adaptations after 10 weeks of energy deficit and after 10 further weeks of nutritional recovery. To do so, we assessed the mRNA levels of the leptin receptor and the main orexigenic and anorexigenic peptides, and their receptors regulated by leptin. Markers of hypothalamic inflammation were assessed as leptin can also participate in this phenomenon. Long-term time-restricted feeding and separation induced significant increase in mRNA levels of hypothalamic orexigenic peptides, while both Y1 and Y5 receptor mRNAs were downregulated. No changes occurred in the mRNA levels of orexin (OX), melanin-concentrating hormone, pro-opiomelanocortin, 26RFa (26-amino acid RF-amide peptide), and their receptors despite an increase in the expression of melanocortin receptors (MC3-R and MC4-R) and OXR1 (OX receptor 1). The refeeding period induced an overexpression of leptin receptor mRNA in the hypothalamus. The other assessed mRNA levels were normalized except for Y2, Y5, MC3-R, and MC4-R, which remained upregulated. No convincing changes were observed in neuroinflammatory markers, even if interleukin-1β mRNA levels were increased in parallel with those of Iba1 (ionized calcium-binding adaptor molecule 1), a marker of microglial activation. Normalization of leptin-regulated functions and hypothalamic gene expressions in refed mice with low plasma leptin levels could be sustained by recalibration of hypothalamic sensitivity to leptin. © 2016 S. Karger AG, Basel.

Enzymes of creatine biosynthesis, arginine and methionine metabolism in normal and malignant cells.

PubMed

Bera, Soumen; Wallimann, Theo; Ray, Subhankar; Ray, Manju

2008-12-01

The creatine/creatine kinase system decreases drastically in sarcoma. In the present study, an investigation of catalytic activities, western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine-synthesizing enzymes l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carcinoma and Sarcoma 180 cells, whereas both enzymes were virtually undetectable in normal muscle. Compared to that of normal animals, these enzymes remained unaffected in the kidney or liver of sarcoma-bearing mice. High activity and expression of mitochondrial arginase II in sarcoma indicated increased ornithine formation. Slightly or moderately higher levels of ornithine, guanidinoacetate and creatinine were observed in sarcoma compared to muscle. Despite the intrinsically low level of creatine in Ehrlich ascites carcinoma and Sarcoma 180 cells, these cells could significantly take up and release creatine, suggesting a functional creatine transport, as verified by measuring mRNA levels of creatine transporter. Transcript levels of arginase II, ornithine-decarboxylase, S-adenosyl-homocysteine hydrolase and methionine-synthase were significantly upregulated in sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180 cells. Overall, the enzymes related to creatine and arginine/methionine metabolism were found to be significantly upregulated in malignant cells. However, the low levels of creatine kinase in the same malignant cells do not appear to be sufficient for the building up of an effective creatine/phosphocreatine pool. Instead of supporting creatine biosynthesis, l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase appear to be geared to support cancer cell metabolism in the direction of polyamine and methionine synthesis because both these compounds are in high demand in proliferating cancer cells.

Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves' disease.

PubMed

Wan Nazaimoon, W M; Khalid, B A

1998-04-01

Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.

Anatomy and Aesthetics of the Labia Minora: The Ideal Vulva?

PubMed

Clerico, C; Lari, A; Mojallal, A; Boucher, F

2017-06-01

Female genital cosmetic surgery is becoming more and more widespread both in the field of plastic and gynaecological surgery. The increased demand for vulvar surgery is spurred by the belief that the vulva is abnormal in appearance. What is normal in terms of labial anatomy? Labia minora enlargement or hypertrophy remains a clinical diagnosis which is poorly defined as it could be considered a variation of the normal anatomy. Enlarged labia minora can cause functional, aesthetic and psychosocial problems. In reality, given the wide variety of vulvar morphology among people, it is a very subjective issue to define the "normal" vulva. The spread of nudity in the general media plays a major role in creating an artificial image and standards with regard to the ideal form. Physicians should be aware that the patient's self-perception of the normal or ideal vulva is highly influenced by the arguably distorted image related to our socio-psychological environment, as presented to us by the general media and internet. As physicians, we have to educate our patients on the variation of vulvar anatomy and the potential risks of these surgeries. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of phosphate binders in moderate CKD.

PubMed

Block, Geoffrey A; Wheeler, David C; Persky, Martha S; Kestenbaum, Bryan; Ketteler, Markus; Spiegel, David M; Allison, Matthew A; Asplin, John; Smits, Gerard; Hoofnagle, Andrew N; Kooienga, Laura; Thadhani, Ravi; Mannstadt, Michael; Wolf, Myles; Chertow, Glenn M

2012-08-01

Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.

[Severe postmenopausal hyperandrogenism due to an ovarian lipoid cell tumor: a case report].

PubMed

Bernasconi, D; Del Monte, P; Marinaro, E; Marugo, A; Marugo, M

2004-03-01

The case of a 62-year-old woman with severe post-menopausal hirsutism is described. Her clinical history revealed regular menstrual periods until menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non-insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism, which had developed in the previous 3 years, with a deeping of the voice. Examination showed android obesity, hypertension and severe hirsutism involving the face and the trunk. Endocrine evaluation pointed out regular adrenal function, serum total and free-testosterone in the adult male range, with normal androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH and FSH were inappropriately low for her post-menopausal age. Computed tomography of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol scan was negative. A further pelvic transvaginal ultrasonography revealed a small cystic formation near the right ovary and a slight increase in the size of the left ovary. The patient underwent bilateral ovariectomy. Histological examination showed a lipoid cell tumor within the left ovary. Immunohistochemical studies were positive for inhibin and cytokeratin. After surgery, serum testosterone fell to normal levels, gonadotropins increased to menopausal levels, confirming that the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism greatly improved. Periodic hormonal tests remained normal and CT of the abdomen and pelvic ultrasonography did not show alterations at a 3 years follow-up.

Parathyroid hormone gene expression in hypophosphatemic rats.

PubMed Central

Kilav, R; Silver, J; Naveh-Many, T

1995-01-01

Phosphate is central to bone metabolism and we have therefore studied whether parathyroid hormone (PTH) is regulated by dietary phosphate in vivo. Weanling rats were fed diets with different phosphate contents for 3 wk: low phosphate (0.02%), normal calcium (0.6%), normal phosphate (0.3%), and calcium (0.6%); high phosphate (1.2%), high calcium (1.2%). The low phosphate diet led to hypophosphatemia, hypercalcemia, and increased serum 1,25(OH)2D3 together with decreased PTH mRNA levels (25 +/- 8% of controls, P < 0.01) and serum immunoreactive PTH (4.7 +/- 0.8: 22.1 +/- 3.7 pg/ml; low phosphate: control, P < 0.05). A high phosphate diet led to increased PTH mRNA levels. In situ hybridization showed that hypophosphatemia decreased PTH mRNA in all the parathyroid cells. To separate the effect of low phosphate from changes in calcium and vitamin D rats were fed diets to maintain them as vitamin D-deficient and normocalcemic despite the hypophosphatemia. Hypophosphatemic, normocalemic rats with normal serum 1,25(OH)2D3 levels still had decreased PTH mRNAs. Nuclear transcript run-ons showed that the effect of low phosphate was posttranscriptional. Calcium and 1,25(OH)2D3 regulate the parathyroid and we now show that dietary phosphate also regulates the parathyroid by a mechanism which remains to be defined. Images PMID:7615802

Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy.

PubMed

Verstovsek, Srdan; Harrison, Claire N; Kiladjian, Jean-Jacques; Miller, Carole; Naim, Ahmad B; Paranagama, Dilan C; Habr, Dany; Vannucchi, Alessandro M

2017-05-01

Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n=110) versus best available therapy (BAT; n=112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate iron status in a prospective study of patients with PV, investigated ruxolitinib effects on 7 serum iron markers and iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline iron deficiency, ruxolitinib was associated with normalization of iron marker levels, compared with lesser improvement with BAT. Iron levels remained stable in ruxolitinib patients with normal iron levels at baseline. Regardless of baseline iron status, treatment with ruxolitinib was associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity, although improvements were generally greater among patients with baseline iron deficiency. The improvements in iron deficiency markers and PROs observed with ruxolitinib are suggestive of clinical benefits that warrant further exploration. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Post-transplant increased levels of serum sCD30 is a marker for prediction of kidney allograft loss in a 5-year prospective study.

PubMed

Delgado, Julio C; Pavlov, Igor Y; Shihab, Fuad S

2009-12-01

Levels of sCD30 represent a biomarker for early outcome in kidney transplantation. The purpose of this study was to determine the role of sCD30 levels for prediction of graft loss in the late post-transplant period. Sera were collected immediately pre-transplant and yearly thereafter for up to 5-year post-transplant in 37 primary renal transplant recipients. Levels of serum sCD30 were tested using a fluorescent microsphere assay. Levels of sCD30 significantly decreased after transplantation and remained normal in 34 patients without graft loss up to 5-year post-transplant. Elevated levels of serum sCD30 preceded the increase of serum creatinine in patients with subsequent graft loss. Elevated levels of serum sCD30 post-transplant might be a marker for predicting subsequent graft loss in the post-transplant period.

Experimental intramammary inoculation with Mycoplasma bovis in vaccinated and unvaccinated cows: effect on milk production and milk quality.

PubMed Central

Boothby, J T; Jasper, D E; Thomas, C B

1986-01-01

The effect of vaccination on milk production was evaluated in vaccinated and control cows experimentally challenged in two of four quarters with live Mycoplasma bovis. During the first three weeks after experimental challenge, six of eight unchallenged quarters on vaccinated cows and seven of eight unchallenged quarters on control cows became infected. Most of these quarters secreted normal milk, with negative California Mastitis Test scores and maintained normal milk production throughout most of the study (although some quarters on control cows remained infected). All challenged quarters became infected, had strong California Mastitis Test reactions, and had a drastic (greater than 85%) loss in milk production. Thereafter, four of eight challenged quarters on control cows remained infected, had mostly positive California Mastitis Test scores, produced mostly normal-appearing milk, and recovered some productive capabilities. By the end of the study no M. bovis could be recovered from challenged quarters on vaccinated cows and the milk appeared mostly normal. The California Mastitis Test scores on these quarters, however, remained elevated and milk production remained very low. PMID:3756674

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice

PubMed Central

Salgueiro, Andréia Caroline Fernandes; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential. PMID:26839634

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

PubMed

Salgueiro, Andréia Caroline Fernandes; Folmer, Vanderlei; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Franco, Jeferson Luis; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women.

PubMed

Kim, Mi Joung; Hwang, Jung Hyun; Ko, Hyun Ji; Na, Hye Bock; Kim, Jung Hee

2015-05-01

The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive and motor functions of iodine-deficient but euthyroid children in Bangladesh do not benefit from iodized poppy seed oil (Lipiodol).

PubMed

Huda, S N; Grantham-McGregor, S M; Tomkins, A

2001-01-01

Iodine supplementation before pregnancy in iodine-deficient women prevents cretinism and neuromotor deficits in their offspring. It is unclear whether iodine supplementation benefits cognitive function in iodine-deficient school-aged children. We therefore conducted a double-blind, randomized, controlled trial of the effects of iodized poppy seed oil (Lipiodol) on cognitive and motor function and weight gain of iodine-deficient school children. The study was conducted with 305 children in grades 1 and 2 from 10 primary schools in two iodine-deficient areas in Bangladesh. The children were stratified by school and grade and randomly assigned to receive 400 mg of oral Lipiodol or a placebo. All children were given a battery of cognitive and motor function tests and had their weights, serum thyroxine (T4) and thyroid-stimulating hormone (TSH) and urinary iodine levels measured before and 4 mo after the intervention. On enrollment, both groups were moderately iodine deficient (median urinary iodine values: placebo group = 3.3 micromol/L, n = 148; iodine group = 3.1 micromol/L, n = 152; goiter prevalence in both groups >95%). However, their T4 and TSH levels were within the normal range. After 4 mo, there was a significant treatment effect on urinary iodine levels (P < 0.0001), but the levels of the treated group were still below normal (median = 7.9 micromol/L). No significant differences were found in T4 and TSH levels, weight gain, cognitive or motor function. The findings suggest that Lipiodol supplementation in moderately iodine-deficient children with normal T4 levels is unlikely to benefit their cognitive function. However, it remains possible that other iodine preparations may have benefits.

Changes in levels of peripheral hormones controlling appetite are inconsistent with hyperphagia in leptin-deficient subjects.

PubMed

Saeed, Sadia; Bech, Paul R; Hafeez, Tayyaba; Alam, Rabail; Falchi, Mario; Ghatei, Mohammad A; Bloom, Stephen R; Arslan, Muhammad; Froguel, Philippe

2014-04-01

Congenital leptin deficiency, a rare genetic disorder due to a homozygous mutation in the leptin gene (LEP), is accompanied by extreme obesity and hyperphagia. A number of gastrointestinal hormones have been shown to critically regulate food intake but their physiological role in hyperphagic response in congenital leptin deficiency has not been elucidated. This study is the first to evaluate the fasting and postprandial profiles of gut-derived hormones in homozygous and heterozygous carriers of LEP mutation. The study subjects from two consanguineous families consisted of five homozygous and eight heterozygous carriers of LEP mutation, c.398delG. Ten wild-type normal-weight subjects served as controls. Fasting and 1-h postprandial plasma ghrelin, glucagon-like peptide (GLP) 1, peptide YY (PYY), leptin and insulin levels were measured by immunoassays. Fasting plasma ghrelin levels in homozygotes remained remarkably unchanged following food consumption (P = 0.33) in contrast to a significant decline in heterozygous (P < 0.03) and normal (P < 0.02) subjects. A significant postprandial increase in PYY was observed in heterozygous (P < 0.02) and control subjects (P < 0.01), but not in the homozygous group (P = 0.22). A postprandial rise in GLP-1 levels was significant (P < 0.02) in all groups. Interestingly, fasting leptin levels in heterozygotes were not significantly different from controls and did not change significantly following meal. Our results demonstrate that gut hormones play little or no physiological role in driving the hyperphagic response of leptin-deficient subjects. In contrast, fasting and postprandial levels of gut hormones in heterozygous mutation carriers were comparable to those of normal-weight controls.

Acacia nilotica leave extract and glyburide: comparison of fasting blood glucose, serum insulin, beta-thromboglubulin levels and platelet aggregation in streptozotocin induced diabetic rats.

PubMed

Asad, Munnaza; Munir, Tahir Ahmad; Afzal, Nasir

2011-03-01

To evaluate the hypoglycaemic and anti-platelet aggregation effect of aqueous methanol extract of Acacia Nilotica (AN) leaves compared with glyburide on streptozotocin induced diabetic rats. Diabetes mellitus was induced in 90 out of 120 albino rats by administering 50 mg/kg body weight (b.w) streptozotocin and was confirmed by measuring fasting blood glucose level >200 mg/dL on 4th post-induction day. The rats were equally divided into 4 groups, A (normal control), B (diabetic control), C (diabetic rats treated with AN extract) and group D (diabetic rats treated with glyburide). The rats of group C and D were given 300 mg/kg b.w AN extract and 900 microgm/kg b.w glyburide respectively for 3 weeks. Blood glucose was measured by glucometer, platelet aggregation by Dia-Med method and insulin and beta-thromboglobulin by ELISA technique. A significant increase (p<0.05) in fasting blood glucose, beta-thromboglobulin and platelet aggregation and a significant decrease (p<0.05) in insulin levels was observed in streptozotocin induced diabetic rats than the normal controls. The rats treated with AN extract and glyburide showed a significant decrease (p<0.05) in fasting blood glucose and increase (p<0.05) in insulin levels than the diabetic control rats. However, the levels in both the treatment groups remained significantly different than the normal controls. A significant decrease (p<0.05) in beta-thromboglobulin levels was seen in diabetic rats treated with glyburide than the diabetic control rats and diabetic rats treated with AN extract. AN leaves extract result into hypoglycaemic and anti-platelet aggregation activity in diabetic rats as that of glyburide.

Iron promotes protein insolubility and aging in C. elegans

PubMed Central

Klang, Ida M.; Schilling, Birgit; Sorensen, Dylan J.; Sahu, Alexandria K.; Kapahi, Pankaj; Andersen, Julie K.; Swoboda, Peter; Killilea, David W.; Gibson, Bradford W.; Lithgow, Gordon J.

2014-01-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity of Caenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation. PMID:25554795

[The investigation of the influence of cryopreservation and inbreeding on the variability of morphological characteristics of the evening-primrose biennial (Oenothera biennis L.)].

PubMed

Chetviverikova, E P; Iashina, S G; Shabaeva, E V; Egorova, E F; Iashina, A V

2005-01-01

The effect of deep freezing of seeds at -196 degrees C (-320.8 degrees Fahrenheit) and inbreeding on the morphological characteristics of the evening-primrose biennal (Oenothera biennis L.), such as the size of plant parts and the amount of fruits, cauline nodes, and generative and vegetative shoots was investigated. The variation coefficients for these characteristics after treatment with low temperatures and inbreeding were calculated. It was shown that the characteristics of plant size show a low and a middle level of variability in the control group. The variation curves for these characteristics are similar to normal distribution curves. After stresses they slightly change or remain invariant. Large adventive shoots show a high level of variability. The distribution of the results in this case significantly differs from the normal. The branching of plants changes after both stress factors: the amount of all kinds of shoots decreases by half or even more.

We Can Change the Natural History of Type 2 Diabetes

PubMed Central

Ratner, Robert E.; Buse, John B.; Kahn, Steven E.

2014-01-01

As diabetes develops, we currently waste the first ∼10 years of the natural history. If we found prediabetes and early diabetes when they first presented and treated them more effectively, we could prevent or delay the progression of hyperglycemia and the development of complications. Evidence for this comes from trials where lifestyle change and/or glucose-lowering medications decreased progression from prediabetes to diabetes. After withdrawal of these interventions, there was no “catch-up”—cumulative development of diabetes in the previously treated groups remained less than in control subjects. Moreover, achieving normal glucose levels even transiently during the trials was associated with a substantial reduction in subsequent development of diabetes. These findings indicate that we can change the natural history through routine screening to find prediabetes and early diabetes, combined with management aimed to keep glucose levels as close to normal as possible, without hypoglycemia. We should also test the hypothesis with a randomized controlled trial. PMID:25249668

Endogenous subclinical hyperthyroidism and cardiovascular system: time to reconsider?

PubMed

Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

2011-05-19

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Exogenous sublinical hyperthyroidism is a thyroid metabolic state caused by L-thyroxine administration. Endogenous subclinical hyperthyroidism is a thyroid metabolic state in patients with autonomously functioning thyroid nodule or multinodular goiter, various forms of thyroiditis, in areas with endemic goiter and particularly in elderly subjects. Endogenous subclinical hyperthyroidism is currently the subject of numerous studies and it yet remains controversial particularly as it relates to its treatment and to cardiovascular impact nevertheless established effects have been demonstrated. Recently, acute myocardial infarction without significant coronary stenoses and recurrent acute pulmonary embolism have been reported associated with subclinical hyperthyroidism without L-thyroxine administration. So, it is very important to recognize and to treat promptly also endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Hypoglycaemia and hypoxic-ischaemic encephalopathy.

PubMed

Boardman, James P; Hawdon, Jane M

2015-04-01

The transition from fetal to neonatal life requires metabolic adaptation to ensure that energy supply to vital organs and systems is maintained after separation from the placental circulation. Under normal conditions, this is achieved through the mobilization and use of alternative cerebral fuels (fatty acids, ketone bodies, and lactate) when blood glucose concentration falls. Severe hypoxia-ischaemia is associated with impaired metabolic adaptation, and animal and human data suggest that levels of hypoglycaemia that are tolerated under normal conditions can be harmful in association with hypoxia-ischaemia. The optimal target blood glucose level for ensuring adequate energy provision in hypoxic-ischaemic encephalopathy (HIE) remains unknown. However, recent data support guidance to maintain a blood glucose concentration of 2.5 mmol/L or more in neonates with signs of acute neurological dysfunction, which includes those with HIE, and this is higher than the accepted threshold of 2 mmol/L in infants without signs of neurological dysfunction or hyperinsulinism. © The Authors. Journal compilation © 2015 Mac Keith Press.

Normal carboxyhaemoglobin level in carbon monoxide poisoning treated with hyperbaric oxygen therapy.

PubMed

Helgeson, Scott A; Wilson, Michael E; Guru, Pramod K

2017-07-24

Throughout the world both intentional and inadvertent exposure to carbon monoxide (CO) remains an important public health issue. While CO poisoning can be lethal, the morbidity is predominantly due to nervous system injury. A previously healthy 22-year-old woman was found unconscious at home by her sister. Her parents were found dead in the house with a recent history of a dysfunctional furnace. She was presumed to have CO poisoning despite an initial carboxyhaemoglobin level of 2.5%. Patient had both clinical and radiological evidence of neurological damage. However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered to a near normal functional status. There is no consensus that exists among treating physicians about the role of hyperbaric oxygen in management of neurological injury. The case described here has significant neurological damage related to CO exposure but improved after HBO therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Expression and rearrangement of the ROS1 gene in human glioblastoma cells

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

Birchmeier, C.; Sharma, S.; Wigler, M.

1987-12-01

The human ROS1 gene, which possibly encodes a growth factor receptor, was found to be expressed in human tumor cell lines. In a survey of 45 different human cell lines, the authors found ROS1 to be expressed in glioblastoma-derived cell lines at high levels and not to be expressed at all, or expressed at very low levels, in the remaining cell lines. The ROS1 gene was present in normal copy numbers in all cell lines that expressed the gene. However, in one particular glioblastoma line, they detected a potentially activating mutation at the ROS1 locus.

Antibody and B Cell Subset Perturbations in Human Immunodeficiency Virus-Uninfected Patients With Cryptococcosis

PubMed Central

Rohatgi, Soma; Nakouzi, Antonio; Carreño, Leandro J; Slosar-Cheah, Magdalena; Kuniholm, Mark H; Wang, Tao; Pappas, Peter G

2018-01-01

Abstract The importance of antibody immunity in protection against Cryptococcus neoformans remains unresolved. We measured serum C neoformans-specific and total antibody levels and peripheral blood B cell subsets of 12 previously healthy patients with cryptococcosis (cases) and 21 controls. Before and after adjustment for age, sex, and race, cryptococcal capsular polysaccharide immunoglobulin G was higher in cases than controls, whereas total B and memory B cell levels were lower. These associations parallel previous findings in patients with human immunodeficiency virus-associated cryptococcosis and suggest that B cell subset perturbations may also associate with disease in previously normal individuals with cryptococcosis. PMID:29354657

Antibody and B Cell Subset Perturbations in Human Immunodeficiency Virus-Uninfected Patients With Cryptococcosis.

PubMed

Rohatgi, Soma; Nakouzi, Antonio; Carreño, Leandro J; Slosar-Cheah, Magdalena; Kuniholm, Mark H; Wang, Tao; Pappas, Peter G; Pirofski, Liise-Anne

2018-01-01

The importance of antibody immunity in protection against Cryptococcus neoformans remains unresolved. We measured serum C neoformans -specific and total antibody levels and peripheral blood B cell subsets of 12 previously healthy patients with cryptococcosis (cases) and 21 controls. Before and after adjustment for age, sex, and race, cryptococcal capsular polysaccharide immunoglobulin G was higher in cases than controls, whereas total B and memory B cell levels were lower. These associations parallel previous findings in patients with human immunodeficiency virus-associated cryptococcosis and suggest that B cell subset perturbations may also associate with disease in previously normal individuals with cryptococcosis.

Electromagnetically induced transparency in the case of elliptic polarization of interacting fields

NASA Astrophysics Data System (ADS)

Parshkov, Oleg M.

2018-04-01

The theoretical investigation results of disintegration effect of elliptic polarized shot probe pulses of electromagnetically induced transparency in the counterintuitive superposed elliptic polarized control field and in weak probe field approximation are presented. It is shown that this disintegration occurs because the probe field in the medium is the sum of two normal modes, which correspond to elliptic polarized pulses with different speeds of propagation. The polarization ellipses of normal modes have equal eccentricities and mutually perpendicular major axes. Major axis of polarization ellipse of one normal mode is parallel to polarization ellipse major axis of control field, and electric vector of this mode rotates in the opposite direction, than electric vector of the control field. The electric vector other normal mode rotates in the same direction that the control field electric vector. The normal mode speed of the first type aforementioned is less than that of the second type. The polarization characteristics of the normal mode depend uniquely on the polarization characteristics of elliptic polarized control field and remain changeless in the propagation process. The theoretical investigation is performed for Λ-scheme of degenerated quantum transitions between 3P0, 3P10 and 3P2 energy levels of 208Pb isotope.

Feature-based attention potentiates recovery of fine direction discrimination in cortically blind patients.

PubMed

Cavanaugh, Matthew R; Barbot, Antoine; Carrasco, Marisa; Huxlin, Krystel R

2017-12-10

Training chronic, cortically-blind (CB) patients on a coarse [left-right] direction discrimination and integration (CDDI) task recovers performance on this task at trained, blind field locations. However, fine direction difference (FDD) thresholds remain elevated at these locations, limiting the usefulness of recovered vision in daily life. Here, we asked if this FDD impairment can be overcome by training CB subjects with endogenous, feature-based attention (FBA) cues. Ten CB subjects were recruited and trained on CDDI and FDD with an FBA cue or FDD with a neutral cue. After completion of each training protocol, FDD thresholds were re-measured with both neutral and FBA cues at trained, blind-field locations and at corresponding, intact-field locations. In intact portions of the visual field, FDD thresholds were lower when tested with FBA than neutral cues. Training subjects in the blind field on the CDDI task improved FDD performance to the point that a threshold could be measured, but these locations remained impaired relative to the intact field. FDD training with neutral cues resulted in better blind field FDD thresholds than CDDI training, but thresholds remained impaired relative to intact field levels, regardless of testing cue condition. Importantly, training FDD in the blind field with FBA lowered FDD thresholds relative to CDDI training, and allowed the blind field to reach thresholds similar to the intact field, even when FBA trained subjects were tested with a neutral rather than FBA cue. Finally, FDD training appeared to also recover normal integration thresholds at trained, blind-field locations, providing an interesting double dissociation with respect to CDDI training. In summary, mechanisms governing FBA appear to function normally in both intact and impaired regions of the visual field following V1 damage. Our results mark the first time that FDD thresholds in CB fields have been seen to reach intact field levels of performance. Moreover, FBA can be leveraged during visual training to recover normal, fine direction discrimination and integration performance at trained, blind-field locations, potentiating visual recovery of more complex and precise aspects of motion perception in cortically-blinded fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety of disclosing amyloid status in cognitively normal older adults.

PubMed

Burns, Jeffrey M; Johnson, David K; Liebmann, Edward P; Bothwell, Rebecca J; Morris, Jill K; Vidoni, Eric D

2017-09-01

Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk. We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure. Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid). There was no difference in depressive symptoms across groups over time. There was a significant group by time interaction in anxiety, although post hoc analyses revealed no group differences at any time point, suggesting a minimal nonsustained increase in anxiety symptoms immediately postdisclosure in the elevated group. Slight but measureable increases in test-related distress were present after disclosure and were related to greater baseline levels of anxiety and depression. Disclosing amyloid imaging results to cognitively normal adults in the clinical research setting with pre- and postdisclosure counseling has a low risk of psychological harm. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Evidence for two populations of hair bundles in the sea anemone, Nematostella vectensis.

PubMed

Menard, Shelcie S; Watson, Glen M

2017-06-01

Cytochalasin D (CD) was employed to disrupt F-actin within stereocilia of anemone hair bundles. CD treatment decreases the abundance of hair bundles (by 85%) while significantly impairing predation. The remaining hair bundles are 'CD-resistant.' Surprisingly, the morphology and F-actin content of resistant hair bundles are comparable to those of untreated controls. However, the resistant hair bundles fail to respond normally to the N-acetylated sugar, NANA, by elongating. Instead, they remain at resting length. Immediately after CD treatment, when only CD-resistant hair bundles are present, nematocyst discharge is normal into targets touched to tentacles in the absence of vibrations (i.e., baseline) but fails to increase normally in the presence of nearby vibrations at 56Hz, a key frequency. After CD treatment, the abundance of hair bundles recovers to control levels within three hours. At 2h after CD treatment, when CD-resistant and CD-sensitive hair bundles are both present, but a full-recovery is not yet complete, somewhat enhanced discharge of nematocysts occurs into targets touched to tentacles in the presence of nearby vibrations at 56Hz (at least as compared to the response of CD-treated animals to contact with test probes in the absence of vibrations). Additionally, at 2h after CD-treatment, prey capture recovers to normal. Thus, two populations of hair bundles may be present on tentacles of sea anemones: those that are CD-resistant and those that are CD-sensitive. The functions of these hair bundles may be distinct. Copyright © 2017 Elsevier Inc. All rights reserved.

Suppression of natural killer cell cytotoxicity in postpartum women: time course and potential mechanisms.

PubMed

Groer, Maureen W; El-Badri, Nagwa; Djeu, Julie; Williams, S Nicole; Kane, Bradley; Szekeres, Karoly

2014-07-01

Little is known about the recovery of the immune system from normal pregnancy and whether the postpartum period is a uniquely adapted immune state. This report extends previous observations from our group of decreased natural killer (NK) cell cytotoxicity in the postpartum period. NK cytotoxicity was measured from 1 week through 9 months postpartum. In addition, NK cytotoxicity was assayed in the presence or absence of pooled plasmas collected from either postpartum or nonpostpartum women. Samples of cells were stained for inhibitory receptors and analyzed by flow cytometry. NK cytotoxicity remained decreased in postpartum women compared to controls through the first 6 postpartum months, returned to normal levels by 9 months, and remained normal at 12 months. NK cytotoxicity during the first 6 months was further inhibited by the addition of pooled plasma to NK cultures from postpartum women, but the addition of pooled plasma from the control group did not affect that group's NK cultures. There were differences in inhibitory receptor staining between the two groups, with decreased CD158a and CD158b and increased NKG2A expression on postpartum NK cells during the first 3 postpartum months. These data suggest that NK cytotoxicity postpartum inhibition lasts 6 months and is influenced by unidentified postpartum plasma components. The effect may also involve receptors on NK cells. © The Author(s) 2013.

CpG location and methylation level are crucial factors for the early detection of oral squamous cell carcinoma in brushing samples using bisulfite sequencing of a 13-gene panel.

PubMed

Morandi, Luca; Gissi, Davide; Tarsitano, Achille; Asioli, Sofia; Gabusi, Andrea; Marchetti, Claudio; Montebugnoli, Lucio; Foschini, Maria Pia

2017-01-01

Oral squamous cell carcinoma (OSCC) is usually diagnosed at an advanced stage and is commonly preceded by oral premalignant lesions. The mortality rates have remained unchanged (50% within 5 years after diagnosis), and it is related to tobacco smoking and alcohol intake. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic value of methylation level in a set of 18 genes by bisulfite next-generation sequencing. With minimally invasive oral brushing, 28 consecutive OSCC, one squamous cell carcinoma with sarcomatoid features, six high-grade squamous intraepithelial lesions (HGSIL), 30 normal contralateral mucosa from the same patients, and 65 healthy donors were evaluated for DNA methylation analyzing 18 target genes by quantitative bisulfite next-generation sequencing. We further evaluated an independent cohort (validation dataset) made of 20 normal donors, one oral fibroma, 14 oral lichen planus (OLP), three proliferative verrucous leukoplakia (PVL), and two OSCC. Comparing OSCC with normal healthy donors and contralateral mucosa in 355 CpGs, we identified the following epigenetically altered genes: ZAP70 , ITGA4 , KIF1A , PARP15 , EPHX3 , NTM , LRRTM1 , FLI1 , MIR193 , LINC00599 , PAX1 , and MIR137HG showing hypermethylation and MIR296 , TERT , and GP1BB showing hypomethylation . The behavior of ZAP70 , GP1BB , H19 , EPHX3 , and MIR193 fluctuated among different interrogated CpGs. The gap between normal and OSCC samples remained mostly the same (Kruskal-Wallis P values < 0.05), but the absolute values changed conspicuously. ROC curve analysis identified the most informative CpGs, and we correctly stratified OSCC and HGSIL from normal donors using a multiclass linear discriminant analysis in a 13-gene panel (AUC 0.981). Only the OSCC with sarcomatoid features was negative. Three contralateral mucosa were positive, a sign of a possible field cancerization. Among imprinted genes, only MIR296 showed loss of imprinting. DNMT1 , TERC , and H19 together with the global methylation of long interspersed element 1 were unchanged. In the validation dataset, values over the threshold were detected in 2/2 OSCC, in 3/3 PVL, and in 2/14 OLP. Our data highlight the importance of CpG location and correct estimation of DNA methylation level for highly accurate early diagnosis of OSCC.

Energetics and biomechanics of locomotion by red kangaroos (Macropus rufus).

PubMed

Kram, R; Dawson, T J

1998-05-01

As red kangaroos hop faster over level ground, their rate of oxygen consumption (indicating metabolic energy consumption) remains nearly the same. This phenomenon has been attributed to exceptional elastic energy storage and recovery via long compliant tendons in the legs. Alternatively, red kangaroos may have exceptionally efficient muscles. To estimate efficiency, we measured the metabolic cost of uphill hopping, where muscle fibers must perform mechanical work against gravity. We found that uphill hopping was much more expensive than level hopping. The maximal rate of oxygen consumption measured (3 ml O2 kg-1 s-1) exceeds all but a few vertebrate species. However, efficiency values were normal, approximately 30%. At faster level hopping speeds the effective mechanical advantage of the extensor muscles of the ankle joint remained the same. Thus, kangaroos generate the same muscular force at all speeds but do so more rapidly at faster hopping speeds. This contradicts a recent hypothesis for what sets the cost of locomotion. The cost of transport (J kg-1 m-1) decreases at faster hopping speeds, yet red kangaroos prefer to use relatively slow speeds that avoid high levels of tendon stress.

Nuclear sequestration of COL1A1 mRNA transcript associated with type I osteogenesis imperfecta (OI)

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

Primorac, D.; Stover, M.L.; McKinstry, M.B.

Previously we identified an OI type I patient with a splice donor mutation that resulted in intron 26 retention instead of exon skipping and sequestration of normal levels of the mutant transcript in the nuclear compartment. Intron retention was consistent with the exon definition hypothesis for splice site selection since the size of the exon-intron-exon unit was less than 300 bp. Furthermore, the retained intron contained in-frame stop codons which is thought to cause the mutant RNA to remain within the nucleus rather than appearing in the cytoplasm. To test these hypotheses, genomic fragments containing the normal sequence or themore » donor mutation were cloned into a collagen minigene and expressed in stably tansfected NIH 3T3 cells. None of the modifications to the normal intron altered the level of RNA that accumulated in the cytoplasm, as expected. However none of the modifications to the mutant intron allowed accumulation of normal levels of mRNA in the cytoplasm. Moreover, in contrast to our findings in the patient`s cells only low levels of mutant transcript were found in the nucleus; a fraction of the transcript did appear in the cytoplasm which had spliced the mutant donor site correctly. Nuclear run-on experiments demonstrated equal levels of transcription from each transgene. Expression of another donor mutation known to cause in-frame exon skipping in OI type IV was accurately reproduced in the minigene in transfected 3T3 cells. Our experience suggests that either mechanism can lead to formation of a null allele possibly related to the type of splicing events surrounding the potential stop codons. Understanding the rules governing inactivation of a collagen RNA transcript may be important in designing a strategy to inactivate a dominate negative mutation associated with the more severe forms of OI.« less

Exertional rhabdomyolysis in a collegiate american football player after preventive cold-water immersion: a case report.

PubMed

Kahanov, Leamor; Eberman, Lindsey E; Wasik, Mitchell; Alvey, Thurman

2012-01-01

To describe a case of exertional rhabdomyolysis in a collegiate American football player after preventive coldwater immersion. A healthy man (19 years old) participated in full-contact football practice followed by conditioning (2.5 hours). After practice, he entered a coach-mandated postpractice cold-water immersion and had no signs of heat illness before developing leg cramps, for which he presented to the athletic training staff. After 10 minutes of repeated stretching, massage, and replacement of electrolyte-filled fluids, he was transported to the emergency room. Laboratory tests indicated a creatine kinase (CK) level of 2545 IU/L (normal range, 45-260 IU/L), CK-myoglobin fraction of 8.5 ng/mL (normal < 6.7 ng/mL), and CK-myoglobin relative index of 30% (normal range, 25%-30%). Myoglobin was measured at 499 ng/mL (normal = 80 ng/mL). The attending physician treated the athlete with intravenous fluids. Exercise-associated muscle cramps, dehydration, exertional rhabdomyolysis. The patient was treated with rest and rehydration. One week after the incident, he began biking and swimming. Eighteen days later, the patient continued to demonstrate elevated CK levels (527 IU/L) but described no other symptoms and was allowed to return to football practice as tolerated. Two months after the incident, his CK level remained high (1900 IU/L). The athlete demonstrated no signs of heat illness upon entering the cold-water immersion but experienced severe leg cramping after immersion, resulting in a diagnosis of exertional rhabdomyolysis. Previously described cases have not linked cold-water immersion with the pathogenesis of rhabdomyolysis. In this football player, CK levels appeared to be a poor indicator of rhabdomyolysis. Our patient demonstrated no other signs of the illness weeks after the incident, yet his elevated CK levels persisted. Cold-water immersion immediately after exercise should be monitored by the athletic training staff and may not be appropriate to prevent muscle damage, given the lack of supporting evidence.

Unique spatial and cellular expression patterns of Hoxa5, Hoxb4 and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia

PubMed Central

Volpe, MaryAnn Vitoria; Wang, Karen Ting Wai; Nielsen, Heber Carl; Chinoy, Mala Romeshchandra

2009-01-01

Background Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 proteins compared to normal lung development. Methods Temporal, spatial and cellular Hoxa5, Hoxb4 and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, 19 fetuses and neonates using western blot and immunohistochemistry. Results Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 isoforms changed with development and further in NT-PH lungs. Compared to normal lungs, Gd19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways. Conclusions Unique spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition. PMID:18553509

Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Sun, Clare; Tian, Xin; Lee, Yuh Shan; Gunti, Sreenivasulu; Lipsky, Andrew; Herman, Sarah E M; Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance; Kardava, Lela; Moir, Susan; Maric, Irina; Valdez, Janet; Soto, Susan; Marti, Gerald E; Farooqui, Mohammed Z; Notkins, Abner L; Wiestner, Adrian; Aue, Georg

2015-11-05

Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P < .0001). To distinguish the effects on clonal B cells from normal B cells, we measured serum free light chains (FLCs). In κ-clonal CLL cases, clonal (κ) FLCs were elevated at baseline and normalized by 6 months. Nonclonal (λ) FLCs, which were often depressed at baseline, increased, suggesting the recovery of normal B cells. Consistently, we observed normal B-cell precursors in the bone marrow and an increase in normal B-cell numbers in the peripheral blood. Patients with superior immune reconstitution, as defined by an increase in serum IgA of ≥50% from baseline to 12 months, had a significantly lower rate of infections (P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330.

Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Sun, Clare; Tian, Xin; Lee, Yuh Shan; Gunti, Sreenivasulu; Lipsky, Andrew; Herman, Sarah E. M.; Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance; Kardava, Lela; Moir, Susan; Maric, Irina; Valdez, Janet; Soto, Susan; Marti, Gerald E.; Farooqui, Mohammed Z.; Notkins, Abner L.; Aue, Georg

2015-01-01

Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P < .0001). To distinguish the effects on clonal B cells from normal B cells, we measured serum free light chains (FLCs). In κ-clonal CLL cases, clonal (κ) FLCs were elevated at baseline and normalized by 6 months. Nonclonal (λ) FLCs, which were often depressed at baseline, increased, suggesting the recovery of normal B cells. Consistently, we observed normal B-cell precursors in the bone marrow and an increase in normal B-cell numbers in the peripheral blood. Patients with superior immune reconstitution, as defined by an increase in serum IgA of ≥50% from baseline to 12 months, had a significantly lower rate of infections (P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330. PMID:26337493

Sensitivity to synchronicity of biological motion in normal and amblyopic vision

PubMed Central

Luu, Jennifer Y.; Levi, Dennis M.

2017-01-01

Amblyopia is a developmental disorder of spatial vision that results from abnormal early visual experience usually due to the presence of strabismus, anisometropia, or both strabismus and anisometropia. Amblyopia results in a range of visual deficits that cannot be corrected by optics because the deficits reflect neural abnormalities. Biological motion refers to the motion patterns of living organisms, and is normally displayed as points of lights positioned at the major joints of the body. In this experiment, our goal was twofold. We wished to examine whether the human visual system in people with amblyopia retained the higher-level processing capabilities to extract visual information from the synchronized actions of others, therefore retaining the ability to detect biological motion. Specifically, we wanted to determine if the synchronized interaction of two agents performing a dancing routine allowed the amblyopic observer to use the actions of one agent to predict the expected actions of a second agent. We also wished to establish whether synchronicity sensitivity (detection of synchronized versus desynchronized interactions) is impaired in amblyopic observers relative to normal observers. The two aims are differentiated in that the first aim looks at whether synchronized actions result in improved expected action predictions while the second aim quantitatively compares synchronicity sensitivity, or the ratio of desynchronized to synchronized detection sensitivities, to determine if there is a difference between normal and amblyopic observers. Our results show that the ability to detect biological motion requires more samples in both eyes of amblyopes than in normal control observers. The increased sample threshold is not the result of low-level losses but may reflect losses in feature integration due to undersampling in the amblyopic visual system. However, like normal observers, amblyopes are more sensitive to synchronized versus desynchronized interactions, indicating that higher-level processing of biological motion remains intact. We also found no impairment in synchronicity sensitivity in the amblyopic visual system relative to the normal visual system. Since there is no impairment in synchronicity sensitivity in either the nonamblyopic or amblyopic eye of amblyopes, our results suggest that the higher order processing of biological motion is intact. PMID:23474301

Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23.

PubMed

Imel, Erik A; Zhang, Xiaoping; Ruppe, Mary D; Weber, Thomas J; Klausner, Mark A; Ito, Takahiro; Vergeire, Maria; Humphrey, Jeffrey S; Glorieux, Francis H; Portale, Anthony A; Insogna, Karl; Peacock, Munro; Carpenter, Thomas O

2015-07-01

In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. The objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH. Two sequential open-label phase 1/2 studies were done. Six academic medical centers were used. Twenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05-0.6 mg/kg); 22 entered a 12-month extension study (0.1-1 mg/kg). KRN23 was injected sc every 28 days. The main outcome measure was the proportion of subjects attaining normal serum Pi and safety. At baseline, mean TmP/GFR, serum Pi, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 1.6 ± 0.4 mg/dL, 1.9 ± 0.3 mg/dL, and 36.6 ± 14.3 pg/mL, respectively. During dose escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3-7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL in 14.8, 37.0, 74.1, and 88.5% of subjects, respectively. During the 12-month extension, peak Pi was in the normal range for 57.9-85.0% of subjects, and ≥25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5 mg/dL in any subject. Although 1,25(OH)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile. Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH.

Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23

PubMed Central

Zhang, Xiaoping; Ruppe, Mary D.; Weber, Thomas J.; Klausner, Mark A.; Ito, Takahiro; Vergeire, Maria; Humphrey, Jeffrey S.; Glorieux, Francis H.; Portale, Anthony A.; Insogna, Karl; Peacock, Munro; Carpenter, Thomas O.

2015-01-01

Context: In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. Objective: The objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH. Design: Two sequential open-label phase 1/2 studies were done. Setting: Six academic medical centers were used. Participants: Twenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05–0.6 mg/kg); 22 entered a 12-month extension study (0.1–1 mg/kg). Intervention: KRN23 was injected sc every 28 days. Main Outcome Measure: The main outcome measure was the proportion of subjects attaining normal serum Pi and safety. Results: At baseline, mean TmP/GFR, serum Pi, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 1.6 ± 0.4 mg/dL, 1.9 ± 0.3 mg/dL, and 36.6 ± 14.3 pg/mL, respectively. During dose escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3–7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL in 14.8, 37.0, 74.1, and 88.5% of subjects, respectively. During the 12-month extension, peak Pi was in the normal range for 57.9–85.0% of subjects, and ≥25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5 mg/dL in any subject. Although 1,25(OH)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile. Conclusions: Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH. PMID:25919461

Environmental lead exposure accelerates progressive diabetic nephropathy in type II diabetic patients.

PubMed

Huang, Wen-Hung; Lin, Ja-Liang; Lin-Tan, Dan-Tzu; Hsu, Ching-Wei; Chen, Kuan-Hsing; Yen, Tzung-Hai

2013-01-01

Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead burden (BLB) (<600  μ g/72 hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80  μ g) and low-normal BLB (<80  μ g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100  μ g increment in BLB and each 10  μ g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72 m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.

Expression and distribution of endocan in human tissues.

PubMed

Zhang, S M; Zuo, L; Zhou, Q; Gui, S Y; Shi, R; Wu, Q; Wei, W; Wang, Y

2012-04-01

Endocan is a novel human endothelial cell specific molecule. Its expression is regulated by cytokines and vascular endothelial growth factor (VEGF). The distribution of endocan in normal human tissues, however, remains unclear. We examined the expression of endocan in normal human tissue using immunohistochemical stains. Endocan was expressed in actively proliferative or neogeneic tissues and cells such as glandular tissues, endothelium of neovasculature, bronchial epithelium, germinal centers of lymph nodes etc. Endocan was not present in silent or resting tissues or cells such as endothelium of great arteries and spleen etc. Our findings suggest that endocan may act as a marker for angiogenesis or oncogenesis and could be regarded as a candidate gene for inflammatory tissue, neoplasia, tumor development and metastasis. The expression level of endocan may assist early diagnosis and prognosis of some tumors.

Recurrent protein-losing enteropathy and tricuspid valve insufficiency in a transplanted heart: a causal relationship?

PubMed

Aggarwal, Sanjeev; Delius, Ralph E; Walters, Henry L; L'Ecuyer, Thomas J

2012-01-01

This case report describes a toddler who developed a protein-losing enteropathy (PLE) 4 years after orthotopic heart transplantation (OHT). He was born with a hypoplastic left heart syndrome for which he underwent a successful Norwood procedure, a Hemi-Fontan palliation, and a Fontan palliation at 18 months of age. Fifteen months following the Fontan operation, he developed a PLE and Fontan failure requiring OHT. Four years after OHT, he developed a severe tricuspid regurgitation and a PLE. His PLE improved after tricuspid valve replacement. It is now 2 years since his tricuspid valve replacement and he remains clinically free of ascites and peripheral edema with a normal serum albumin level. His prosthetic tricuspid valve is functioning normally. © 2011 Wiley Periodicals, Inc.

Iodinated contrast media can induce long-lasting oxidative stress in hemodialysis patients.

PubMed

Hwang, Seun Deuk; Kim, Yoon Ji; Lee, Sang Heun; Cho, Deok Kyu; Cho, Yun Hyeong; Moon, Sung Jin; Lee, Sang Choel; Yoon, Soo Young

2013-11-01

Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population. We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days. In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure. Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients.

Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging.

PubMed

Bültmann, Eva; Nägele, Thomas; Lanfermann, Heinrich; Klose, Uwe

2017-01-01

We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic.

A protocol for resuscitation of severe burn patients guided by transpulmonary thermodilution and lactate levels: a 3-year prospective cohort study.

PubMed

Sánchez, Manuel; García-de-Lorenzo, Abelardo; Herrero, Eva; Lopez, Teresa; Galvan, Beatriz; Asensio, María; Cachafeiro, Lucia; Casado, Cesar

2013-08-15

The use of urinary output and vital signs to guide initial burn resuscitation may lead to suboptimal resuscitation. Invasive hemodynamic monitoring may result in over-resuscitation. This study aimed to evaluate the results of a goal-directed burn resuscitation protocol that used standard measures of mean arterial pressure (MAP) and urine output, plus transpulmonary thermodilution (TPTD) and lactate levels to adjust fluid therapy to achieve a minimum level of preload to allow for sufficient vital organ perfusion. We conducted a three-year prospective cohort study of 132 consecutive critically burned patients. These patients underwent resuscitation guided by MAP (>65 mmHg), urinary output (0.5 to 1 ml/kg), TPTD and lactate levels. Fluid therapy was adjusted to achieve a cardiac index (CI) >2.5 L/minute/m² and an intrathoracic blood volume index (ITBVI) >600 ml/m2, and to optimize lactate levels. Statistical analysis was performed using mixed models. We also used Pearson or Spearman methods and the Mann-Whitney U-test. A total of 98 men and 34 women (mean age, 48 ± 18 years) was studied. The mean total body surface area (TBSA) burned was 35% ± 22%. During the early resuscitation phase, lactate levels were elevated (2.58 ± 2.05 mmol/L) and TPTD showed initial hypovolemia by the CI (2.68 ± 1.06 L/minute/m²) and the ITBVI (709 ± 254 mL/m²). At 24 to 32 hours, the CI and lactic levels were normalized, although the ITBVI remained below the normal range (744 ± 276 ml/m²). The mean fluid rate required to achieve protocol targets in the first 8 hours was 4.05 ml/kg/TBSA burned, which slightly increased in the next 16 hours. Patients with a urine output greater than or less than 0.5 ml/kg/hour did not show differences in heart rate, mean arterial pressure, CI, ITBVI or lactate levels. Initial hypovolemia may be detected by TPTD monitoring during the early resuscitation phase. This hypovolemia might not be reflected by blood pressure and hourly urine output. An adequate CI and tissue perfusion can be achieved with below-normal levels of preload. Early resuscitation guided by lactate levels and below-normal preload volume targets appears safe and avoids unnecessary fluid input.

Use of labelled triolein, vitamin A, and D-xylose in the diagnosis of malabsorption 1

PubMed Central

Wormsley, K. G.

1963-01-01

This paper discusses the type of results given by a group of test procedures used in the study of small intestinal dysfunction. While the chemical estimation of faecal fat remains the most valuable criterion for the laboratory detection of malabsorption, the occurrence of abnormal faecal or blood radioactivity also denotes the presence of malabsorption, although some patients with staetorrhoea appear to `absorb' labelled triolein normally. Analysis of data from the other tests shows that steatorrhoea is not necessarily present in patients who give abnormal results and that the presence of malabsorption does not preclude a normal capacity for handling the test substances. These reservations impair the value of the vitamin A and xylose `tolerance' tests and serum carotene levels as screening procedures for the determination of malabsorption states. On the other hand, these tests show patterns of results which are useful in differentiating idiopathic from secondary steatorrhoea, since patients with secondary malabsorption often handle one or more of these test substances normally. PMID:14058268

eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor cells

PubMed Central

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R.; Beadnell, Thomas C.; Schwertfeger, Kathryn L.; Benyumov, Alexey O.; Manivel, J. Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B.; Polunovsky, Vitaly A.

2015-01-01

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biological outputs remains unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased cell self-renewal, triggered DNA replication stress, and induced formation of pre-malignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biological output in lactating mammary glands, and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its pro-neoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. PMID:25524901

eIF4E threshold levels differ in governing normal and neoplastic expansion of mammary stem and luminal progenitor cells.

PubMed

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R; Beadnell, Thomas C; Schwertfeger, Kathryn L; Benyumov, Alexey O; Manivel, J Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2015-02-15

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its proneoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. ©2014 American Association for Cancer Research.

DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin.

PubMed

Gao, Liqin; Yang, Bin; Zhang, Hairong; Ou, Qishui; Lin, Yulan; Zhang, Mei; Zhang, Zhenhuan; Kim, Sunghee; Wu, Bing; Wang, Zeng; Fu, Lengxi; Lin, Jingan; Chen, Ruiqing; Lan, Ruilong; Chen, Junying; Chen, Wei; Chen, Long; Zhang, Hengshan; Han, Deping; Chen, Jingrong; Okunieff, Paul; Lin, Jianhua; Zhang, Lurong

2018-02-16

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis ( n = 134), SIRS ( n = 60) and normal adults ( n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1-2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis ( r s = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1-2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.

Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats

PubMed Central

Xin, Fengjiao; Yu, Xiaobing

2018-01-01

Background & Aims Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. Methods A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. Results We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck, G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3–V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Phascolarctobacterium, and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio, which produce lipopolysaccharide (LPS). The abundance of Lachnospiraceae was negatively correlated with the blood glucose response after a glucose load. Conclusion In summary, diabetic rats have different gut microbiota from control rats. Inulin treatment can alleviate gut microbiota dysbiosis in T2D model rats. Moreover, inulin treatment enhanced serum GLP-1 level to suppress IL-6 secretion and production and hepatic gluconeogenesis, resulted in moderation of insulin tolerance. PMID:29507837

Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats.

PubMed

Zhang, Qian; Yu, Hongyue; Xiao, Xinhua; Hu, Ling; Xin, Fengjiao; Yu, Xiaobing

2018-01-01

Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck , G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3-V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae , Phascolarctobacterium , and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio , which produce lipopolysaccharide (LPS). The abundance of Lachnospiraceae was negatively correlated with the blood glucose response after a glucose load. In summary, diabetic rats have different gut microbiota from control rats. Inulin treatment can alleviate gut microbiota dysbiosis in T2D model rats. Moreover, inulin treatment enhanced serum GLP-1 level to suppress IL-6 secretion and production and hepatic gluconeogenesis, resulted in moderation of insulin tolerance.

Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.

PubMed

Eirin, Alfonso; Zhu, Xiang-Yang; Ferguson, Christopher M; Riester, Scott M; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O

2015-01-19

Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.

Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy.

PubMed

Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Ito, Takanori; Maeda, Atsuyuki; Kaneoka, Yuji; Kagebayashi, Chiaki; Satomura, Shinji

2014-06-01

We investigated changes in highly sensitive lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (hsAFP-L3) measured using a novel method and its predictive ability for prognosis in patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy, comparing to other HCC tumor markers, that is, AFP, des-gamma-carboxy prothrombin (DCP), and AFP-L3 measured with conventional method (cAFP-L3). AFP, DCP, and AFP-L3 including both cAFP-L3 and hsAFP-L3 were measured before and after curative hepatectomy in 187 patients. The percentage of patients with elevated tumor marker levels pre- and postoperatively was compared, and recurrence-free and overall survival rates were analyzed based on changes in tumor markers. The percentages of patients with elevated AFP, DCP, and cAFP-L3 decreased postoperatively. In contrast, the percentage of patients with elevated hsAFP-L3 did not decrease postoperatively. Both recurrence-free and overall survival rates were significantly lower in patients whose tumor marker levels remained elevated postoperatively than patients without tumor marker elevation postoperatively. Recurrence-free and overall survival rates of patients in whom hsAFP-L3 became elevated postoperatively despite normal preoperative hsAFP-L3 levels were significantly lower than those of patients with normal hsAFP-L3 postoperatively, and were similar to those of patients with persistent elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many patients postoperatively, but not for hsAFP-L3. The elevation of hsAFP-L3 identifies patients with poor prognosis despite the normalization of AFP and DCP. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Stress inhibits PYY secretion in obese and normal weight women.

PubMed

Kiessl, Gundula R R; Laessle, Reinhold G

2016-06-01

The impact of stress on circulating levels of appetite-regulating hormones remains largely unknown. The aim of this study was to analyze the effect of acute psychosocial stress on the gut hormone peptide YY (PYY) secretion in obese and normal weight women. Therefore, we compared pre- and post-prandial plasma PYY secretion of 42 obese and 43 normal weight women in a repeated measure randomized controlled laboratory experiment. PYY and cortisol concentrations were measured and ratings of stress and satiety were also recorded in response to a psychological stressor (Trier Social Stress Test, TSST). PYY samples were collected in the fasting state both before participating in the TSST and before a control session. Participants had a standardized meal after the TSST and control session, respectively. PYY was measured both 30 and 60 min after the TSST and control session, respectively. Stress inhibited PYY secretion as well as food intake in all women, but did not influence subjective satiety perception. The present data indicate that despite of lower PYY levels the subjects' requirement to overeat was not increased. From an evolutionary perspective this finding is adaptive. After stress the organism is prepared for fight or flight reaction, whereas not primarily necessary functions are inhibited. Therefore, increased food intake during stress would be dysfunctional.

Maternal Nanos-Dependent RNA Stabilization in the Primordial Germ Cells of Drosophila Embryos.

PubMed

Sugimori, Seiko; Kumata, Yuji; Kobayashi, Satoru

2018-01-01

Nanos (Nos) is an evolutionary conserved protein expressed in the germline of various animal species. In Drosophila, maternal Nos protein is essential for germline development. In the germline progenitors, or the primordial germ cells (PGCs), Nos binds to the 3' UTR of target mRNAs to repress their translation. In contrast to this prevailing role of Nos, here we report that the 3' UTR of CG32425 mRNA mediates Nos-dependent RNA stabilization in PGCs. We found that the level of mRNA expressed from a reporter gene fused to the CG32425 3' UTR was significantly reduced in PGCs lacking maternal Nos (nos PGCs) as compared with normal PGCs. By deleting the CG32425 3' UTR, we identified the region required for mRNA stabilization, which includes Nos-binding sites. In normal embryos, CG32425 mRNA was maternally supplied into PGCs and remained in this cell type during embryogenesis. However, as expected from our reporter assay, the levels of CG32425 mRNA and its protein product expressed in nos PGCs were lower than in normal PGCs. Thus, we propose that Nos protein has dual functions in translational repression and stabilization of specific RNAs to ensure proper germline development. © 2017 Japanese Society of Developmental Biologists.

A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function.

PubMed

Safaeian, Navid; David, Tim

2013-10-01

The oxygen exchange and correlation between the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) in the cortical capillary levels for normal and pathologic brain functions remain the subject of debate. A 3D realistic mesoscale model of the cortical capillary network (non-tree like) is constructed using a random Voronoi tessellation in which each edge represents a capillary segment. The hemodynamics and oxygen transport are numerically simulated in the model, which involves rheological laws in the capillaries, oxygen diffusion, and non-linear binding of oxygen to hemoglobin, respectively. The findings show that the cerebral hypoxia due to a significant decreased perfusion (as can occur in stroke) can be avoided by a moderate reduction in oxygen demand. Oxygen extraction fraction (OEF) can be an important indicator for the brain oxygen metabolism under normal perfusion and misery-perfusion syndrome (leading to ischemia). The results demonstrated that a disproportionately large increase in blood supply is required for a small increase in the oxygen demand, which, in turn, is strongly dependent on the resting OEF. The predicted flow-metabolism coupling in the model supports the experimental studies of spatiotemporal stimulations in humans by positron emission tomography and functional magnetic resonance imaging.

A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function

PubMed Central

Safaeian, Navid; David, Tim

2013-01-01

The oxygen exchange and correlation between the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) in the cortical capillary levels for normal and pathologic brain functions remain the subject of debate. A 3D realistic mesoscale model of the cortical capillary network (non-tree like) is constructed using a random Voronoi tessellation in which each edge represents a capillary segment. The hemodynamics and oxygen transport are numerically simulated in the model, which involves rheological laws in the capillaries, oxygen diffusion, and non-linear binding of oxygen to hemoglobin, respectively. The findings show that the cerebral hypoxia due to a significant decreased perfusion (as can occur in stroke) can be avoided by a moderate reduction in oxygen demand. Oxygen extraction fraction (OEF) can be an important indicator for the brain oxygen metabolism under normal perfusion and misery-perfusion syndrome (leading to ischemia). The results demonstrated that a disproportionately large increase in blood supply is required for a small increase in the oxygen demand, which, in turn, is strongly dependent on the resting OEF. The predicted flow-metabolism coupling in the model supports the experimental studies of spatiotemporal stimulations in humans by positron emission tomography and functional magnetic resonance imaging. PMID:23921901

Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway.

PubMed

Osumi, Tomoo; Awazu, Midori; Fujimura, Eriko; Yamazaki, Fumito; Hashiguchi, Akinori; Shimada, Hiroyuki

2013-06-01

Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1-32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1α, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement. Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.

Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.

PubMed

Schaufler, Jörg; Ronovsky, Marianne; Savalli, Giorgia; Cabatic, Maureen; Sartori, Simone B; Singewald, Nicolas; Pollak, Daniela D

2016-01-01

Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.

Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels

NASA Technical Reports Server (NTRS)

Steffen, J. M.; Musacchia, X. J.

1987-01-01

The effect of whole-body suspension on the time course and the extent of plasma corticosterone changes and the tissue sensitivity to glucocorticoids were investigated in rats subjected to seven days of whole-body suspension. Plasma corticosterone increased significantly on the first and the third days of suspension, but returned to control levels by day seven. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity (evaluated in competitive-displacement experiments). In controls, receptor site concentration in the slow-twitch soleus was comparable to that in the fast-twitch gastrocnemius and plantaris, but was significantly less than in the extensor; seven days of suspension resulted in significant differential effects on muscle receptor levels. The largest increase in receptor concentration was observed in the soleus in which it remained elevated after the receptor levels in other muscles returned to normal.

S-ADENOSYLMETHIONINE IN LIVER HEALTH, INJURY, AND CANCER

PubMed Central

Lu, Shelly C.; Mato, José M.

2013-01-01

S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well. PMID:23073625

Decreased panicle-derived indole-3-acetic acid reduces gibberellin A1 level in the uppermost internode, causing panicle enclosure in male sterile rice Zhenshan 97A.

PubMed

Yin, Changxi; Gan, Lijun; Ng, Denny; Zhou, Xie; Xia, Kai

2007-01-01

Cytoplasmic male sterile (CMS) rice Zhenshan 97A (ZS97A) has been widely used in hybrid rice production in China. However, ZS97A suffers from serious panicle enclosure, which blocks normal pollination and greatly reduces seed production of hybrid rice. Little is known about the cause of panicle closure in ZS97A. In this study, it was found that the occurrence of cytoplasmic male sterility caused a deficiency of indole-3-acetic acid (IAA) in ZS97A panicles, and less IAA was provided to the uppermost internode (UI). Further, it was found that the decreased panicle-derived IAA caused a gibberellin A(1) (GA(1)) deficiency in the UI by the down-regulation of OsGA3ox2 transcript level. Reduced GA(1) level in the UI led to decreases of both cell number and cell elongation, resulting in a shortened UI. The shortened UI was unable to push the panicle out of the flag leaf sheath that remained normal, which resulted in panicle enclosure in ZS97A. These findings suggest that decreased panicle-derived IAA reduces the GA(1) level in the UI, causing panicle enclosure in CMS rice ZS97A.

The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes.

PubMed

Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

2016-03-07

As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies.

The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes

PubMed Central

Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

2016-01-01

As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies. PMID:26949191

Positive end-expiratory pressure at minimal respiratory elastance represents the best compromise between mechanical stress and lung aeration in oleic acid induced lung injury.

PubMed

Carvalho, Alysson Roncally S; Jandre, Frederico C; Pino, Alexandre V; Bozza, Fernando A; Salluh, Jorge; Rodrigues, Rosana; Ascoli, Fabio O; Giannella-Neto, Antonio

2007-01-01

Protective ventilatory strategies have been applied to prevent ventilator-induced lung injury in patients with acute lung injury (ALI). However, adjustment of positive end-expiratory pressure (PEEP) to avoid alveolar de-recruitment and hyperinflation remains difficult. An alternative is to set the PEEP based on minimizing respiratory system elastance (Ers) by titrating PEEP. In the present study we evaluate the distribution of lung aeration (assessed using computed tomography scanning) and the behaviour of Ers in a porcine model of ALI, during a descending PEEP titration manoeuvre with a protective low tidal volume. PEEP titration (from 26 to 0 cmH2O, with a tidal volume of 6 to 7 ml/kg) was performed, following a recruitment manoeuvre. At each PEEP, helical computed tomography scans of juxta-diaphragmatic parts of the lower lobes were obtained during end-expiratory and end-inspiratory pauses in six piglets with ALI induced by oleic acid. The distribution of the lung compartments (hyperinflated, normally aerated, poorly aerated and non-aerated areas) was determined and the Ers was estimated on a breath-by-breath basis from the equation of motion of the respiratory system using the least-squares method. Progressive reduction in PEEP from 26 cmH2O to the PEEP at which the minimum Ers was observed improved poorly aerated areas, with a proportional reduction in hyperinflated areas. Also, the distribution of normally aerated areas remained steady over this interval, with no changes in non-aerated areas. The PEEP at which minimal Ers occurred corresponded to the greatest amount of normally aerated areas, with lesser hyperinflated, and poorly and non-aerated areas. Levels of PEEP below that at which minimal Ers was observed increased poorly and non-aerated areas, with concomitant reductions in normally inflated and hyperinflated areas. The PEEP at which minimal Ers occurred, obtained by descending PEEP titration with a protective low tidal volume, corresponded to the greatest amount of normally aerated areas, with lesser collapsed and hyperinflated areas. The institution of high levels of PEEP reduced poorly aerated areas but enlarged hyperinflated ones. Reduction in PEEP consistently enhanced poorly or non-aerated areas as well as tidal re-aeration. Hence, monitoring respiratory mechanics during a PEEP titration procedure may be a useful adjunct to optimize lung aeration.

Characteristics of locomotion, muscle strength, and muscle tissue in regenerating rat skeletal muscles.

PubMed

Iwata, Akira; Fuchioka, Satoshi; Hiraoka, Koichi; Masuhara, Mitsuhiko; Kami, Katsuya

2010-05-01

Although numerous studies have aimed to elucidate the mechanisms used to repair the structure and function of injured skeletal muscles, it remains unclear how and when movement recovers following damage. We performed a temporal analysis to characterize the changes in movement, muscle function, and muscle structure after muscle injury induced by the drop-mass technique. At each time-point, movement recovery was determined by ankle kinematic analysis of locomotion, and functional recovery was represented by isometric force. As a histological analysis, the cross-sectional area of myotubes was measured to examine structural regeneration. The dorsiflexion angle of the ankle, as assessed by kinematic analysis of locomotion, increased after injury and then returned to control levels by day 14 post-injury. The isometric force returned to normal levels by day 21 post-injury. However, the size of the myotubes did not reach normal levels, even at day 21 post-injury. These results indicate that recovery of locomotion occurs prior to recovery of isometric force and that functional recovery occurs earlier than structural regeneration. Thus, it is suggested that recovery of the movement and function of injured skeletal muscles might be insufficient as markers for estimating the degree of neuromuscular system reconstitution.

Quality of Golden papaya stored under controlled atmosphere conditions.

PubMed

Martins, Derliane Ribeiro; de Resende, Eder Dutra

2013-10-01

This work evaluated physicochemical parameters of Golden papaya stored under refrigeration in controlled atmospheres. The fruits were kept at 13  in chambers containing either 3 or 6% O2 combined with 6%, 10% or 15% CO2. Moreover, a normal atmosphere was produced with 20.8% O2 and 0.03% CO2 with ethylene scrubbing, and a control treatment was used with ambient conditions. Evaluations were performed at the following times: before storage, after 30 days of storage in controlled atmosphere, and after removal from controlled atmosphere and storage for 7 days in the cold room. At the lower O2 levels and higher CO2 levels, the ripening rate was decreased. The drop in pulp acidity was avoided after 30 days of storage at 3% O2, but the fruits reached normal acidity after removal from controlled atmosphere and storage for 7 days in the cold room. The reducing sugars remained at a higher concentration after 30 days under 3% O2 and 15% CO2 even 7 days after removal from controlled atmosphere and storage in the cold room. This atmosphere also preserved the content of ascorbic acid at a higher level.

Thyroid dysfunctions of prematurity and their impacts on neurodevelopmental outcome.

PubMed

Chung, Mi Lim; Yoo, Han Wok; Kim, Ki-Soo; Lee, Byong Sop; Pi, Soo-Young; Lim, Gina; Kim, Ellen Ai-Rhan

2013-01-01

Thyroid dysfunction is very common and is associated with neurodevelopmental impairments in preterm infants. This study was conducted to determine the incidence and natural course of various thyroid dysfunctions and their impacts on neurodevelopmental outcomes among premature infants. A total of 177 infants were enrolled who were born at <34 weeks or whose birth weight was <1500 g and who underwent repeat thyroid function tests. We analyzed how various thyroid dysfunctions affected neurodevelopmental outcomes at 18 months of corrected age. Thyroid dysfunction was noted in 88 infants. Hypothyroxinemia was observed in 23 infants, and their thyroid function was influenced by variable clinical factors. Free T4 levels were all normalized without thyroxine medication, and neurodevelopmental outcomes were not affected. In contrast, hyperthyrotropinemia was not associated with other clinical factors. Among 58 subjects who had hyperthyrotropinemia, only 31 infants showed normal thyroid-stimulating hormone (TSH) levels at follow-up tests. The remaining 27 infants had persistently high TSH levels, which significantly and poorly influenced the neurodevelopmental outcomes. Thyroid dysfunction is common among preterm infants. With the exception of persistent hyperthyrotropinemia, it generally does not affect neurodevelopmental outcomes. However, the beneficial effects of thyroid hormone therapy in patients with persistent hyperthyrotropinemia merits further study.

Brain natriuretic peptide and right heart dysfunction after heart transplantation.

PubMed

Talha, Samy; Charloux, Anne; Piquard, François; Geny, Bernard

2017-06-01

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vitamin D deficiency in multiple sclerosis: Should testing and treatment be based on racial background?

PubMed

Avasarala, Jagannadha; Zachariah, Phenu

2015-11-15

Maintaining adequate levels of vitamin D may have a protective effect and lower the risk of multiple sclerosis (MS). For patients with MS, maintaining an adequate level of vitamin D level is probably associated with lessening of the frequency and severity of their symptoms. However, what remains unclear is whether if this is true across all racial/ethnic backgrounds. In African-Americans (AAs) this effect is not only absent but curiously enough, low levels of vitamin D do not matter since the bioavailability of this molecule in AA subjects is normal. It is this paradox that led to this brief report and we suggest more research and database construction based on race/ethnicity be done, as a first step to understand the biological mechanisms that confer or negate the effect of vitamin D levels in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Renal Cortical Pyruvate Depletion during AKI

PubMed Central

Johnson, Ali C.M.; Becker, Kirsten

2014-01-01

Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15–60 minutes; 0–18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury. PMID:24385590

Early superoxide dismutase alterations during SV40-transformation of human fibroblasts.

PubMed

Bravard, A; Hoffschir, F; Sabatier, L; Ricoul, M; Pinton, A; Cassingena, R; Estrade, S; Luccioni, C; Dutrillaux, B

1992-11-11

The expression of superoxide dismutases (SOD) 1 and 2 was studied in 4 clones of human fibroblasts after their infection by simian virus 40 (SV40), in parallel with the alterations of chromosomes 21 and chromosome 6q arms, carrying the genes that encode for SOD1 and SOD2 respectively. For all clones, a similar scheme with 2 main phases was observed for both chromosome and SOD variations. The first phase, defined as the pre-crisis phase, was characterized by chromosomal instability, but maintenance of normal numbers of chromosome 6q arms and chromosomes 21. The level of SOD2 mRNA was high, while SOD2 activity and immunoreactive protein were low. SOD1 protein and activity were decreased. In the second phase, defined as the post-crisis phase, the accumulation of clonal chromosomal rearrangements led to the loss of 6q arms, while the number of chromosomes 21 remained normal. SOD2 mRNA level was decreased and SOD2 immunoreactive protein and activity remained low. SOD1 protein and activity increased with passages, reaching values similar to those of control cells at late passages. As in established SV40-transformed human fibroblast cell lines, good correlation was found between SOD2 activity and the relative number of 6q arms. These results allow us to reconstruct the sequence of events leading to the decrease of SOD2, a possible tumor-suppressor gene, during the process of SV40-transformation of human fibroblasts.

Ground-water conditions and studies in Georgia, 2001

USGS Publications Warehouse

Leeth, David C.; Clarke, John S.; Craigg, Steven D.; Wipperfurth, Caryl J.

2003-01-01

The U.S. Geological Survey (USGS) collects ground-water data and conducts studies to monitor hydrologic conditions, to better define ground-water resources, and address problems related to water supply and water quality. Data collected as part of ground-water studies include geologic, geophysical, hydraulic property, water level, and water quality. A ground-water-level network has been established throughout most of the State of Georgia, and ground-water-quality networks have been established in the cities of Albany, Savannah, and Brunswick and in Camden County, Georgia. Ground-water levels are monitored continuously in a network of wells completed in major aquifers of the State. This network includes 17 wells in the surficial aquifer, 12 wells in the upper and lower Brunswick aquifers, 73 wells in the Upper Floridan aquifer, 10 wells in the Lower Floridan aquifer and underlying units, 12 wells in the Claiborne aquifer, 1 well in the Gordon aquifer, 11 wells in the Clayton aquifer, 11 wells in the Cretaceous aquifer system, 2 wells in Paleozoic-rock aquifers, and 7 wells in crystalline-rock aquifers. In this report, data from these 156 wells were evaluated to determine whether mean-annual ground-water levels were within, below, or above the normal range during 2001, based on summary statistics for the period of record. Information from these summaries indicates that water levels during 2001 were below normal in almost all aquifers monitored, largely reflecting climatic effects from drought and pumping. In addition, water-level hydrographs for selected wells indicate that water levels have declined during the past 5 years (since 1997) in almost all aquifers monitored, with water levels in some wells falling below historical lows. In addition to continuous water-level data, periodic measurements taken in 52 wells in the Camden County-Charlton County area, and 65 wells in the city of Albany-Dougherty County area were used to construct potentiometric-surface maps for the Upper Floridan aquifer. Ground-water quality in the Upper Floridan aquifer is monitored in the cities of Albany, Savannah, and Brunswick and in Camden County; and monitored in the Lower Floridan aquifer in the Savannah and Brunswick areas. In the Albany area since 1998, nitrate concentrations in the Upper Floridan aquifer have increased in 4 of the 11 wells monitored, and in 1 well, concentrations were above the U.S. Environmental Protection Agency's (USEPA) 10 milligrams per liter (mg/L) drinking-water standard. In the Savannah area, chloride concentration in water from four wells in the Upper Floridan aquifer showed no appreciable change during 2001, remaining within the USEPA 250 mg/L drinking-water standard; in seven wells completed in the Lower Floridan aquifer and in underlying zones, the chloride concentration remained above the drinking-water standard, with one well showing an increase over previous years. In the Brunswick area, water samples from 66 wells completed in the Upper or Lower Floridan aquifers were collected during June 2001 and analyzed for chloride. A map showing chloride concentrations in the Upper Floridan aquifer during June 2001 indicates that concentrations remained above USEPA drinking-water standards across a 2-square-mile area. In the north Brunswick area, chloride concentrations in the Upper Floridan aquifer continued to increase, whereas in the south Brunswick area, concentrations continued to decrease. In the Camden County area, chloride concentrations in six wells completed in the Upper Floridan aquifer remained within drinking-water standards. With the exception of one well, concentrations remained the same and were below 40 mg/L. In one well, concentrations showed a sharp decline during 2001, but remained above 130 mg/L. Ongoing studies during 2001 include evaluation of agricultural chemicals in shallow ground water in southwestern Georgia; evaluation of saltwater intrusion and water-level and water-quality m

Central and peripheral effects of chronic food restriction and weight restoration in the rat.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L; Tao, Erin E

2009-02-01

Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis

PubMed Central

Zhang, Zhiqiang; Li, Zhennan; Zou, Chen; Zhang, Jingjing; Zhu, Yi; Miao, Yi

2015-01-01

Background/aims: Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis. Methodology: To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis). Results: The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). Conclusions: The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies. PMID:26550120

Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

PubMed

Zhang, Wei; Chen, Lulu; Zhang, Luqing; Xiao, Ming; Ding, Jiong; Goltzman, David; Miao, Dengshun

2015-02-19

Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Activation of RAS family genes in urothelial carcinoma.

PubMed

Boulalas, I; Zaravinos, A; Karyotis, I; Delakas, D; Spandidos, D A

2009-05-01

Bladder cancer is the fifth most common malignancy in men in Western society. We determined RAS codon 12 and 13 point mutations and evaluated mRNA expression levels in transitional cell carcinoma cases. Samples from 30 human bladder cancers and 30 normal tissues were analyzed by polymerase chain reaction/restriction fragment length polymorphism and direct sequencing to determine the occurrence of mutations in codons 12 and 13 of RAS family genes. Moreover, we used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profile of RAS genes in bladder cancer specimens compared to that in adjacent normal tissues. Overall H-RAS mutations in codon 12 were observed in 9 tumor samples (30%). Two of the 9 patients (22%) had invasive bladder cancer and 7 (77%) had noninvasive bladder cancer. One H-RAS mutation (11%) was homozygous and the remaining 89% were heterozygous. All samples were WT for K and N-RAS oncogenes. Moreover, 23 of 30 samples (77%) showed over expression in at least 1 RAS family gene compared to adjacent normal tissue. K and N-RAS had the highest levels of over expression in bladder cancer specimens (50%), whereas 27% of transitional cell carcinomas demonstrated H-RAS over expression relative to paired normal tissues. Our results underline the importance of H-RAS activation in human bladder cancer by codon 12 mutations. Moreover, they provide evidence that increased expression of all 3 RAS genes is a common event in bladder cancer that is associated with disease development.

Proecdysial changes in serum ecdysone titers, gastrolith formation, and limb regeneration following molt induction by limb autotomy and/or eyestalk removal in the land crab, Gecarcinus lateralis

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

McCarthy, J.F.; Skinner, D.M.

1977-01-01

The changes in serum ecdysone titers, gastrolith deposition, and limb regeneration were monitored at each stage of the molt cycle in the land crab, Gecarcinus lateralis. Animals were induced to molt by multiple-limb autotomy or eyestalk removal. The presence of ..cap alpha..-ecdysone and b-ecdysone (20-hydroxyecdysone) in the animals' serum was demonstrated chromatographically. ..beta..-ecdysone was the major circulating ecdysone, while ..cap alpha..-ecdysone was present only at very low concentrations. Four other components reacting with the ecdysone antiserum were separated chromatographically; one of these, a nonpolar compound, became a major component of the serum ecdysones at the time of maximum hormone titers.more » Ecdysone titers in the serum remained at the level characteristic of intermolt (approximately 10 ng/ml) during basal regeneration and rose linearly during the premolt period, reaching a maximum when regeneration of limbs had ceased and exoskeleton was deposited. Ecdysone decreased during stages D/sub 3/ and D/sub 4/, approaching intermolt levels at the time of ecdysis, where they remained through postmolt stages A and B. The patterns of premolt changes in ecdysone titers, gastroliths, and regeneration were very similar in ''normal'' animals (stimulated to molt by the loss of eight pereiopods) and in animals without eyestalks; however, in crabs without eyestalks, the changes were completed in about half the time as in crabs with eyestalks. Basal regeneration is associated with low ecdysone levels even in crabs without eyestalks. The normal sequence of proecdysial events is not initiated until the completion of basal regeneration. It is suggested that there exists a yet-unidentified mechanism outside the eyestalk capable of preventing increases in ecdysone titers while limbs engage in basal regeneration.« less

The impact of signal normalization on seizure detection using line length features.

PubMed

Logesparan, Lojini; Rodriguez-Villegas, Esther; Casson, Alexander J

2015-10-01

Accurate automated seizure detection remains a desirable but elusive target for many neural monitoring systems. While much attention has been given to the different feature extractions that can be used to highlight seizure activity in the EEG, very little formal attention has been given to the normalization that these features are routinely paired with. This normalization is essential in patient-independent algorithms to correct for broad-level differences in the EEG amplitude between people, and in patient-dependent algorithms to correct for amplitude variations over time. It is crucial, however, that the normalization used does not have a detrimental effect on the seizure detection process. This paper presents the first formal investigation into the impact of signal normalization techniques on seizure discrimination performance when using the line length feature to emphasize seizure activity. Comparing five normalization methods, based upon the mean, median, standard deviation, signal peak and signal range, we demonstrate differences in seizure detection accuracy (assessed as the area under a sensitivity-specificity ROC curve) of up to 52 %. This is despite the same analysis feature being used in all cases. Further, changes in performance of up to 22 % are present depending on whether the normalization is applied to the raw EEG itself or directly to the line length feature. Our results highlight the median decaying memory as the best current approach for providing normalization when using line length features, and they quantify the under-appreciated challenge of providing signal normalization that does not impair seizure detection algorithm performance.

Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol.

PubMed

Archer, D F; Thomas, M A; Conard, J; Merkatz, R B; Creasy, G W; Roberts, K; Plagianos, M; Blithe, D; Sitruk-Ware, R

2016-01-01

Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150mcg Nestorone® (NES) and 15mcg ethinyl estradiol (EE). A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. NES/EE CVR for up to 13cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC. Copyright © 2016 Elsevier Inc. All rights reserved.

Aging-associated changes in L-type calcium channels in the left atria of dogs.

PubMed

Gan, Tian-Yi; Qiao, Weiwei; Xu, Guo-Jun; Zhou, Xian-Hui; Tang, Bao-Peng; Song, Jian-Guo; Li, Yao-Dong; Zhang, Jian; Li, Fa-Peng; Mao, Ting; Jiang, Tao

2013-10-01

Action potential (AP) contours vary considerably between the fibers of normal adult and aged left atria. The underlying ionic and molecular mechanisms that mediate these differences remain unknown. The aim of the present study was to investigate whether the L-type calcium current (I Ca.L ) and the L-type Ca 2+ channel of the left atria may be altered with age to contribute to atrial fibrillation (AF). Two groups of mongrel dogs (normal adults, 2-2.5 years old and older dogs, >8 years old) were used in this study. The inducibility of AF was quantitated using the cumulative window of vulnerability (WOV). A whole-cell patch-clamp was used to record APs and I Ca.L in left atrial (LA) cells obtained from the two groups of dogs. Protein and mRNA expression levels of the a1C (Cav1.2) subunit of the L-type calcium channel were assessed using western blotting and quantitative PCR (qPCR), respectively. Although the resting potential, AP amplitude and did not differ with age, the plateau potential was more negative and the APD 90 was longer in the aged cells compared with that in normal adult cells. Aged LA cells exhibited lower peak I Ca.L current densities than normal adult LA cells (P<0.05). In addition, the Cav1.2 mRNA and protein expression levels in LA cells were decreased in the aged group compared with those in the normal adult group. The lower AP plateau potential and the decreased I Ca.L of LA cells in aged dogs may contribute to the slow and discontinuous conduction of the left atria. Furthermore, the reduction of the expression levels of Cav1.2 with age may be the molecular mechanism that mediates the decline in I Ca.L with increasing age.

[Clinical use of RU 486: control of the menstrual cycle and effect on the hypophyseal-adrenal axis].

PubMed

Gaillard, R C; Herrmann, W

1983-01-01

RU 486 is a synthetic 19 norsteroid with a great affinity for progesterone and glucocorticosteroid receptors. The antiprogesterone activity of RU 486 permits interruption of the luteal phase of the menstrual cycle and of early pregnancy, while the antiglucocorticosteroid activity interrupts the feedback mechanisms of cortisol at the hypothalamic-pituitary axis. 11 women aged 18-34 years who were 6-8 weeks pregnant were given daily doses of 200 mg of sensation of lipothymia. Blood pressure and laboratory test results remained normal. The daily increase of beta human chorionic gonadotropin (HCG) and progesterone was stopped by the antiprogesterone. It has been demonstrated in vitro that RU 486 inhibits secretion of beta HCG by cells of trophoblastic origin. 2 weeks after expulsion of the products of conception, the blood levels of beta HCG, progesterone, and estradiol had returned to nonpregnant values and ovarian activity was normal in women not using oral contraceptives. The reason for failure of expulsion in 2 cases was not known. RU 486 was also used to interrupt the luteal phase of normal menstrual cycles in 3 young women. 50 mg/day of RU 486 starting on the 22nd day was sufficient to induce bleeding within 48 hours. Studies using RU 486 50 mg/day beginning on the 10th cycle day indicate that progesterone plays a central and follicular role during the preovulatory period. The antiglucocorticosteroid activity of RU 486 was observed in pregnant women who received the abortifacient dose of 200 mg/day. The 8 a.m. plasma level of ACTH and beta-LPH cortisol remained elevated for thee 4 days of treatment. Nonpregnant women receiving 50 mg of RU 486 for 4 days beginning on the 22nd cycle day had no change in the level of hypophyseal-adrenal hormones.dd Tests in young male volunteers showed that RU 486 amplified circadian rhythms of the hypophysealadrenal axis, affecting specifically the morning hormonal levels without influencing afternoon levels. A test in which RU 486 was used to antagonize the inhibition producedd by dexamethasone during a test of suppression of the hypophyseal-adrenal axis confirmed that the antiglucocorticosteroid effect of RU 486 is produced at the level of the glucocorticosteroid receptors. The antiglucocorticosteroid effect is independent of the antiprogesterone effect. RU 486 may be utilizable in fertility control, to control undesirable effects of steroids in cases of hypercorticism, and perhaps eventually to test the hypophyseal-adrenal axis.

Immunosuppression Enhances Oncolytic Adenovirus Replication and Antitumor Efficacy in the Syrian Hamster Model

PubMed Central

Thomas, Maria A; Spencer, Jacqueline F; Toth, Karoly; Sagartz, John E; Phillips, Nancy J; Wold, William SM

2012-01-01

We recently described an immunocompetent Syrian hamster model for oncolytic adenoviruses (Ads) that permits virus replication in tumor cells as well as some normal tissues. This model allows exploration of interactions between the virus, tumor, normal organs, and host immune system that could not be examined in the immunodeficient or nonpermissive animal models previously used in the oncolytic Ad field. Here we asked whether the immune response to oncolytic Ad enhances or limits antitumor efficacy. We first determined that cyclophosphamide (CP) is a potent immunosuppressive agent in the Syrian hamster and that CP alone had no effect on tumor growth. Importantly, we found that the antitumor efficacy of oncolytic Ads was significantly enhanced in immunosuppressed animals. In animals that received virus therapy plus immunosuppression, significant differences were observed in tumor histology, and in many cases little viable tumor remained. Notably, we also determined that immunosuppression allowed intratumoral virus levels to remain elevated for prolonged periods. Although favorable tumor responses can be achieved in immunocompetent animals, the rate of virus clearance from the tumor may lead to varied antitumor efficacy. Immunosuppression, therefore, allows sustained Ad replication and oncolysis, which leads to substantially improved suppression of tumor growth. PMID:18665155

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Comparison between the effects of inhaled isoprenaline and fenoterol on plasma cyclic AMP and heart rate in normal subjects.

PubMed Central

Fairfax, A J; Rehahn, M; Jones, D; O'Malley, B

1984-01-01

The time course of changes in plasma cyclic AMP, heart rate and bronchial tone after inhalation of fenoterol or isoprenaline from a dose-metered aerosol are reported in a group of normal subjects. After isoprenaline, plasma cyclic AMP increased rapidly reaching a peak by 10 min and returned to basal levels within 60 min. A rapid, transient rise in heart rate occurred that was maximal by 5 min and returned to a basal level by 45 min. After fenoterol, the changes in cyclic AMP and heart rate were of much longer duration. The rise in plasma cyclic AMP was slower in onset and of greater magnitude than for isoprenaline, reaching a peak by 20 min and remaining above basal level for more than 6 h. The maximum increase in heart rate after fenoterol was less than that observed with isoprenaline but an elevated rate persisted for 4 h after inhalation of fenoterol. Fenoterol is known to have a longer duration of action as a bronchodilator in comparison with isoprenaline. The prolonged rise in plasma cyclic AMP in normal subjects given inhaled fenoterol may reflect this long duration of action. The concomitant rise in heart rate, however, suggests that the duration of plasma cyclic AMP response may in part be due to the systemic effect of the fraction of inhaled fenoterol known to be absorbed via the buccal and intestinal routes. PMID:6322828

The impact of obesity on pentraxin 3 and inflammatory milieu to acute aerobic exercise.

PubMed

Slusher, Aaron L; Mock, J Thomas; Whitehurst, Michael; Maharaj, Arun; Huang, Chun-Jung

2015-02-01

Pentraxin 3 (PTX3) has recently been linked to obesity-associated inflammation, serving as a cardioprotective modulator against cardiovascular disease (CVD). Aerobic exercise has been shown to enhance plasma PTX3 levels; however, the impact of obesity on PTX3 response to exercise remains unknown. Therefore, this study sought to examine whether obese subjects would have an attenuated plasma PTX3 response compared to normal-weight subjects following acute aerobic exercise. The relationship of plasma PTX3 with pro-inflammatory cytokines (IL-6 and TNF-α) was also examined. Twenty healthy subjects (10 obese [4 males and 6 females] and 10 normal-weight [4 males, 6 females]) performed 30min of continuous submaximal aerobic exercise. At baseline, obese subjects exhibited approximately 40% lower plasma PTX3 and a 7-fold greater IL-6 concentration compared to normal-weight subjects. In response to exercise, no difference was observed in PTX3 or IL-6 as indicated by area-under-the-curve "with respect to increase" (AUCi) analyses. Furthermore, PTX3 AUCi was positively correlated with cardiorespiratory fitness levels (VO(2max)) (r=0.594, p=0.006), even after controlling for body mass index. These findings suggest that in addition to obesity-associated complications, low cardiorespiratory fitness levels could impact exercise-induced PTX3 elevations, thereby potentially diminishing PTX3's effects of anti-inflammation and/or cardioprotection. Copyright © 2015 Elsevier Inc. All rights reserved.

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

PubMed Central

Vidal Fortuny, J.; Belfontali, V.; Sadowski, S. M.; Karenovics, W.; Guigard, S.

2016-01-01

Background Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Methods Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Results Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. Conclusion PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID:26864909

Changes in the predominant human Lactobacillus flora during in vitro fertilisation

PubMed Central

Jakobsson, Tell; Forsum, Urban

2008-01-01

Background Signature matching of nucleotide sequences in the V1 and V3 regions 16S rRNA genes using pyrosequencing technology is a powerful tool for typing vaginal Lactobacilli to the species level and has been used for investigating the vaginal microbial niche. Methods This study has characterized the normal cultivable vaginal Lactobacillus flora at varying estradiol levels in plasma; the study comprised 17 patients undergoing ovarian stimulation for In Vitro Fertilization (IVF) treatment. The vaginal status of each participant was initially assessed as normal according to Amsel and Nugent criteria. Results L. crispatus, L. gasseri and/or L. jensenii were present in 10 of the patients throughout the study period, and little variation among these three species was encountered in individual patients. The flora of three women was dominated by L. delbrüeckii, L. rhamnosus or L. vaginalis. One woman exhibited a dominance of L. iners. The flora of the remaining three women were initially dominated by L. rhamnosus or L. reuteri, but as their estrogen levels rose, their flora composition altered, to become dominated by one of the three species most common in a normal, healthy vagina. Conclusion Signature matching of nucleotide sequences in the V1 and V3 regions of 16S rRNA genes is a discriminative tool for the study of vaginal Lactobacilli and can be used to track the Lactobacillus flora under a variety of physiological conditions. PMID:18590533

Woman with virilizing congenital adrenal hyperplasia and Leydig cell tumor of the ovary.

PubMed

Fernández-García Salazar, Rosario; Muñoz-Darias, Carmen; Haro-Mora, Juan Jesús; Almaraz, M Cruz; Audí, Laura; Martínez-Tudela, Juana; Yahyaoui, Raquel; Esteva, Isabel

2014-08-01

We report the case of a 36-year-old woman with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, and corticosteroid replacement therapy since birth. She manifested persistent virilization and high testosterone levels that were attributed to nonadherence to medical treatment. The patient was referred to our gender unit for genitoplastic surgery. We recommended the patient for left oophorectomy after detecting an ovarian mass. Pathologic findings confirmed an ovarian hilus cell tumor. Testosterone levels fell back to normal and masculinization disappeared but ACTH remained elevated. This case represents a very rare type of primary ovarian tumor that must be considered in persistent virilizing symptoms in women with CAH.

Premenstrual dysphoric disorder: neuroendocrine interferences.

PubMed

Poiană, Cătălina; Muşat, Mădălina; Carsote, Mara; Chiriţă, Corina

2009-01-01

Premenstrual dysphoric disorder (PMDD) consists in severe cognitive and mood changes, more aggressive as seen in premenstrual syndrome (PMS). These two syndromes are situated at the border between gynecology and psychiatry but the link between the two domains remains the neuroendocrine underlying mechanisms. In present, there are some molecular systems certainly proved as being involved, like estrogens. The hormonal pattern consists not in different levels of the hormones but different response to normal hormonal levels. The cyclical biochemical triggers are related to neurotransmitters as serotonin, endorphin and gamma-amino butyric acid (GABA). The heritability of the syndrome is sustained by genetic polymorphism in ESR1 gene. Thus, the PMDD is the result of multiple disturbances regarding neuroendocrine systems.

[Effect of stress on nucleic acid metabolism in the rat spleen and liver after a flight on the Kosmos-1129 biosatellite].

PubMed

Komolova, G S; Troitskaia, E N; Egorov, I A; Tigranian, R A

1982-01-01

Changes in nucleic acid metabolism of the spleen and liver of rats flown for 18.5 days on Cosmos-112 were investigated. Postflight changes in the liver RNA synthesis after an additional stress effect (immobilization) in the flown rats were expressed to a lesser degree than in the controls. The DNA synthesis remained essentially at the preflight level. The tissue content of nucleic acids suggests that postflight the dystrophic changes induced by the additional stress effect increased. It is very likely that an exposure to space flight effects contributes to the depletion of compensatory mechanisms maintaining the normal level of metabolic processes.

Impact of Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus on the Amyloid Cascade

PubMed Central

Moriya, Masao; Miyajima, Masakazu; Nakajima, Madoka; Ogino, Ikuko; Arai, Hajime

2015-01-01

The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid β-peptide (Aβ), by measuring the levels of Alzheimer’s disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived Aβ-like peptides (APL1β) (a surrogate marker for Aβ). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP) and Aβ38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ≥ 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in Aβ38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1β25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPPα and sAPPβ, Aβ38 and 42, and APL1β25 and 28, with shifts from sAPPβ to sAPPα, from APL1β28 to 25, and from Aβ42 to 38 in all patients with iNPH. Our results suggest that Aβ production remained unchanged by the shunt procedure because the levels of sAPP and APL1β were unchanged. Moreover, the shift of Aβ from oligomer to monomer due to the shift of Aβ42 (easy to aggregate) to Aβ38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to increased Aβ levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of Aβ in patients with iNPH. PMID:25821958

Anterior Cruciate Ligament Injury, Reconstruction, and the Optimization of Outcome

PubMed Central

Bliss, James Philip

2017-01-01

Anterior cruciate ligament reconstruction (ACLR) provides an established surgical intervention to control pathological tibiofemoral translational and rotational movement. ACLR is a safe and reproducible intervention, but there remains an underlying rate of failure to return to preinjury sporting activity levels. Postoperative pathological laxity and graft reinjury remain concerns. Previously, unrecognized meniscal lesions, disruption of the lateral capsule, and extracapsular structures offer potential avenues to treat and to therefore improve kinematic outcome and functional results, following reconstruction. Addressing laterally based injuries may also improve the durability of intraarticular ACLR. Improving the anterior cruciate ligament (ACL) graft replication of the normal ACL attachment points on the femur and the tibia, using either double bundle or anatomical single bundle techniques, improves kinematics, which may benefit outcome and functionality, following reconstruction. PMID:28966384

Peach gum polysaccharides improve the spermatogenesis of KKAy mice with impaired reproduction system.

PubMed

Qian, Li; Wang, Wenjun; Song, Jie; Chen, Dezhong

2017-03-01

Peach gum polysaccharides (PGPs) exhibit antioxidant and antibacterial activities. Nevertheless, the effect of PGPs on the spermatogenesis of KKAy mice with impaired reproduction system remains undetermined. PGPs were extracted with hot water. KKAy mice were randomly divided into two groups, namely, control and PGPs (treated with 100 mg/kg PGPs). Oral administration of PGPs decreased the levels of serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, plasma insulin, and nitrate nitrogen level in the testes of KKAy mice. Moreover, treatment with PGPs increased the sperm density, sperm movement, rate of normal sperm morphology, protein expression level, and superoxide dismutase activity. PGPs can effectively protect the spermatogenesis of KKAy mice with impaired reproduction system. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Changes in parental weight and smoking habits and offspring adiposity: data from the HUNT-study.

PubMed

Fasting, Magnus Hølmo; Nilsen, Tom Ivar Lund; Holmen, Turid Lingaas; Vik, Torstein

2011-06-01

Adverse parental life-style habits are associated with offspring adiposity, but it is unclear how changes in these habits affect offspring adiposity. Thus, the aim of this study was to assess how parental change in body weight, smoking habits and levels of physical activity were associated with adiposity in their children. The study population consisted of 3 681 adolescents and their parents from the Nord-Trøndelag-Health-Study (HUNT). The parents participated in the two first waves of HUNT (HUNT-1:1984-86, HUNT-2:1995-97), where information on anthropometry, smoking habits and physical activity were obtained. The adolescents participated in the Youth-Part of HUNT-2. We used logistic regression to calculate odds-ratios (ORs) for adolescent offspring overweight according to parental change in body-weight, smoking habits and physical activity, adjusting for these factors in both parents, as well as for socioeconomic status and adolescent age and sex. Children of parents who changed weight from normal weight to overweight from HUNT-1 to HUNT-2 had higher OR for overweight in adolescence than children of parents who remained normal weight (mothers: 1.9 [95% CI: 1.4,2.5], fathers: 2.2 [95% CI: 1.5,3.0]). Children of mothers who reduced their weight from overweight to normal weight had no higher OR for overweight in adolescence than mothers who remained normal weight (OR: 1.0; 95% CI: 0.2, 4.7). Children of mothers who quit smoking (OR: 0.5; 95% CI: 0.3, 0.8) had lower OR for overweight in adolescence than children of mothers who persisted in smoking. Healthy changes in parental life-style during childhood are associated with lower occurrence of offspring overweight in adolescence.

High normal urine albumin-to-creatinine ratio predicts development of hypertension in Korean men.

PubMed

Park, Sung Keun; Moon, Soo Young; Oh, Chang-Mo; Ryoo, Jae-Hong; Park, Min Suk

2014-01-01

Microalbuminuria is known as a risk factor for hypertension. Recently it was suggested that urine albumin-to-creatinine ratio (UACR), even within the normal range, can be associated with hypertension, but the temporal relationship between normal range UACR and hypertension was not confirmed. Therefore the aim of this study was to verify an association between normal range UACR and the development of hypertension in Korean men. This prospective cohort study was performed on 1,284 initially non-hypertensive Korean men. The total follow-up period was 4,109.5 person-years and the mean follow-up period was 3.2±1.51 years. Cox proportional hazards model was used to estimate the hazard ratios (HR) for the risk of hypertension development. After adjusting for multiple covariates, the HR (95% confidence interval [CI]) for incident hypertension, comparing the second to the fourth quartiles of UACR level to the first quartile, were 1.35 (95% CI: 0.93-1.97), 1.55 (95% CI: 1.07-2.25) and 1.89 (95% CI: 1.31-2.71), respectively (P for trend=0.001). High UACR within the normal range was significantly associated with hypertension development. Furthermore, this association remained significant after adjusting for multiple baseline covariates. 

Iron, transferrin and myelinogenesis

NASA Astrophysics Data System (ADS)

Sergeant, C.; Vesvres, M. H.; Devès, G.; Baron, B.; Guillou, F.

2003-09-01

Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

Changes in circulating IGF1 receptor stimulating activity do not parallel changes in total IGF1 during GH treatment of GH-deficient adults.

PubMed

Varewijck, Aimee J; Lamberts, Steven W J; van der Lely, A J; Neggers, Sebastian J C M M; Hofland, Leo J; Janssen, Joseph A M J L

2015-08-01

Previously we demonstrated that IGF1 receptor stimulating activity (IGF1RSA) offers advantages in diagnostic evaluation of adult GH deficiency (GHD). It is unknown whether IGF1RSA can be used to monitor GH therapy. To investigate the value of circulating IGF1RSA for monitoring GH therapy. 106 patients (54 m; 52 f) diagnosed with GHD were included; 22 were GH-naïve, 84 were already on GH treatment and discontinued therapy 4 weeks before baseline values were established. IGF1RSA was determined by the IGF1R kinase receptor activating assay, total IGF1 by immunoassay (Immulite). GH doses were titrated to achieve total IGF1 levels within the normal range. After 12 months, total IGF1 and IGF1RSA increased significantly (total IGF1 from 8.1 (95% CI 7.3-8.9) to 14.9 (95% CI 13.5-16.4) nmol/l and IGF1RSA from 115 (95% CI 104-127) to 181 (95% CI 162-202) pmol/l). After 12 months, total IGF1 normalized in 81% of patients, IGF1RSA in 51% and remained below normal in more than 40% of patients in whom total IGF1 had normalized. During 12 months of GH treatment, changes in IGF1RSA did not parallel changes in total IGF1. Despite normalization of total IGF1, IGF1RSA remained subnormal in a considerable proportion of patients. At present our results have no short-term consequences for GH therapy of GHD patients. However, based on our findings we propose future studies to examine whether titrating GH dose against IGF1RSA results in a better clinical outcome than titrating against total IGF1. © 2015 European Society of Endocrinology.

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes.

PubMed

O'Dwyer, David N; Norman, Katy C; Xia, Meng; Huang, Yong; Gurczynski, Stephen J; Ashley, Shanna L; White, Eric S; Flaherty, Kevin R; Martinez, Fernando J; Murray, Susan; Noth, Imre; Arnold, Kelly B; Moore, Bethany B

2017-04-25

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals.

PubMed

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A; Sachdev, Perminder S

2012-01-01

Apolipoproteins have recently been implicated in the etiology of Alzheimer's disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

PubMed Central

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A.; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A.; Sachdev, Perminder S.

2012-01-01

Objectives Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. Methods 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. Results At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Conclusions Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals. PMID:22701550

Identification and evaluation of reference genes for accurate gene expression normalization of fresh and frozen-thawed spermatozoa of water buffalo (Bubalus bubalis).

PubMed

Ashish, Shende; Bhure, S K; Harikrishna, Pillai; Ramteke, S S; Muhammed Kutty, V H; Shruthi, N; Ravi Kumar, G V P P S; Manish, Mahawar; Ghosh, S K; Mihir, Sarkar

2017-04-01

The quantitative real time PCR (qRT-PCR) has become an important tool for gene-expression analysis for a selected number of genes in life science. Although large dynamic range, sensitivity and reproducibility of qRT-PCR is good, the reliability majorly depend on the selection of proper reference genes (RGs) employed for normalization. Although, RGs expression has been reported to vary considerably within same cell type with different experimental treatments. No systematic study has been conducted to identify and evaluate the appropriate RGs in spermatozoa of domestic animals. Therefore, this study was conducted to analyze suitable stable RGs in fresh and frozen-thawed spermatozoa. We have assessed 13 candidate RGs (BACT, RPS18s, RPS15A, ATP5F1, HMBS, ATP2B4, RPL13, EEF2, TBP, EIF2B2, MDH1, B2M and GLUT5) of different functions and pathways using five algorithms. Regardless of the approach, the ranking of the most and the least candidate RGs remained almost same. The comprehensive ranking by RefFinder showed GLUT5, ATP2B4 and B2M, MDH1 as the top two stable and least stable RGs, respectively. The expression levels of four heat shock proteins (HSP) were employed as a target gene to evaluate RGs efficiency for normalization. The results demonstrated an exponential difference in expression levels of the four HSP genes upon normalization of the data with the most stable and the least stable RGs. Our study, provides a convenient RGs for normalization of gene-expression of key metabolic pathways effected during freezing and thawing of spermatozoa of buffalo and other closely related bovines. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute high-intensity interval exercise induces comparable levels of circulating cell-free DNA and Interleukin-6 in obese and normal-weight individuals.

PubMed

Ferrandi, Peter J; Fico, Brandon G; Whitehurst, Michael; Zourdos, Michael C; Bao, Fanchen; Dodge, Katelyn M; Rodriguez, Alexandra L; Pena, Gabriel; Huang, Chun-Jung

2018-06-01

Obesity is associated with lipid aggregation in adipocytes and macrophage infiltration, leading to increased oxidative stress and inflammation. Increased cell-free DNA (cfDNA) concentrations have been observed in clinical conditions of systemic inflammation. While the beneficial effects of regular physical activity on the release of circulating cfDNA still remain unknown, acute intense exercise has been shown to increase inflammatory cytokines and cfDNA concentrations in normal-weight individuals. Therefore, the primary purpose of this study was to examine the effect of acute high-intensity interval Exercise (HIIE) on plasma cfDNA and interleukin-6 (IL-6) responses in obese and normal-weight subjects. Fourteen male subjects (7 obese and 7 normal-weight) participated in an acute HIIE protocol (30 min, 4x4min @ 80% - 90% of VO 2max ) on a treadmill. Between HIIE intervals, subjects performed 3 min of active recovery at 50-60% VO 2max . Blood samples were collected prior to, immediately following exercise, and one hour into recovery for measurements of plasma cfDNA and IL-6. Our results demonstrated a significant elevation in plasma cfDNA immediately following acute HIIE in both obese and normal-weight subjects. A comparable elevation in the concentration of plasma IL-6 was also found between two groups in response to acute HIIE. Furthermore, the level of plasma cfDNA was not correlated with IL-6 either at baseline or in response to acute HIIE. These findings may support the utilization of HIIE as a time-efficient exercise protocol to understand the obesity-associated cfDNA and inflammatory responses. Published by Elsevier Inc.

Toxicity following methoxyflurane anaesthesia. IV. The role of obesity and the effect of low dose anaesthesia on fluoride metabolism and renal function.

PubMed

Samuelson, P N; Merin, R G; Taves, D R; Freeman, R B; Calimlim, J F; Kumazawa, T

1976-09-01

Seven obese and five normal weight patients were studied before, during and after one hour of methoxyflurane-nitrous oxide anaesthesia during peripheral surgical operations and compared with eight patients of normal weight anaesthetized with nitrous oxide-meperidine and d-tubocurare. Estimates were made of renal function, including serum and urinary electrolytes, osmolarity, uric acid, urea and creatinine. Renal clearances for the latter three substances were also calculated. Serum and urinary inorganic and organic fluoride concentrations were measured, as were renal clearances. This low dose methoxyflurane anaesthesia resulted only in a decrease in uric acid clearance among all the measures, when compared to the meperidine-nitrous oxide controls. The clearance of uric acid remained depressed for longer in the obese patients, but otherwise they did not differ from the normal weight patients. It is possible but not proven that depressed uric acid clearance may be related to the organic fluoride metabolite and an early indicator of methoxyflurane renal toxicity. The previously documented biotransformation of methoxyflurane was seen in this study. A double peak in serum inorganic fluoride was shown in all patients but one. Rather large differences in peak levels of serum inorganic fluoride occurred. The only significant difference between the obese and normal weight patients as far as fluoride metabolism was concerned was a greater variability in the serum inorganic fluoride levels in the obese patients. It would appear that the obese patient metabolizes methoxyflurane in a quantitatively if not qualitatively different fashion than the normal weight patient, perhaps because of fatty infiltration of the liver. Caution is advised in the use of methoxyflurane for more than 90 minutes of low concentration administration in view of the unpredictability of the biotransformation.

Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infancia y Medio Ambiente Cohort, Spain.

PubMed

León, Gemma; Murcia, Mario; Rebagliato, Marisa; Álvarez-Pedrerol, Mar; Castilla, Ane M; Basterrechea, Mikel; Iñiguez, Carmen; Fernández-Somoano, Ana; Blarduni, Elizabeth; Foradada, Carles M; Tardón, Adonina; Vioque, Jesús

2015-03-01

Maternal clinical thyroid disorders can cause reproductive complications. However, the effects of mild thyroid dysfunctions are not yet well established. The aim was to evaluate the association of maternal thyroid function during the first half of pregnancy with birthweight and preterm delivery. We analysed data on 2170 pregnant women and their children from a prospective population-based cohort study in four Spanish areas. Mid-gestation maternal serum and urine samples were gathered to determine thyroid-stimulating hormone (TSH), free thyroxine (fT4 ), and urinary iodine concentration (UIC). Thyroid status was defined according to percentile distribution as: euthyroid (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4  < 5 th percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal or <5th percentile), hyperthyroxinaemia (fT4  > 95 th percentile and TSH normal), and hyperthyroidism (TSH < 5 th percentile and fT4 normal or >95th percentile). Response variables were birthweight, small and large for gestational age (SGA/LGA), and preterm delivery. An inverse association of fT4 and TSH with birthweight was found, the former remaining when restricted to euthyroid women. High fT4 levels were also associated with an increased risk of SGA [odds ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight was higher in the hypothyroxinaemic group (β = 109, P < 0.01). Iodine intake and UIC were not associated with birth outcomes. High maternal fT4 levels during the first half of pregnancy were related to lower birthweight and increased risk of SGA newborns, suggesting that maternal thyroid function may affect fetal growth, even within the normal range. © 2015 John Wiley & Sons Ltd.

Review of the gastrointestinal tract: from macro to micro.

PubMed

Reed, Kathleen K; Wickham, Rita

2009-02-01

To review the normal anatomy and physiology of the gastrointestinal (GI) tract, the malignant transformations in GI cancers, and the rationale for targeted therapy for these cancers. Published articles, book chapters and web sources. Oncology nurses require an understanding of normal GI anatomy and physiology, along with an understanding of malignant transformations at the cellular and molecular level, to effectively educate and care for the patient with a diagnosis of a GI cancer. Challenges for the oncology nurse include continuing education related to GI cancer, the development of effective patient education skills, ensuring safe administration of oral agents and remaining current regarding GI clinical trial opportunities. Education of nursing colleagues, development of an area of expertise through specialization, and development of leadership skills are opportunities associated with practicing in the dynamic environment of oncology nursing.

A 3 Year-Old Male Child Ingested Approximately 750 Grams of Elemental Mercury.

PubMed

Uysalol, Metin; Parlakgül, Güneş; Yılmaz, Yasin; Çıtak, Agop; Uzel, Nedret

2016-07-01

The oral ingestion of elemental mercury is unlikely to cause systemic toxicity, as it is poorly absorbed through the gastrointestinal system. However, abnormal gastrointestinal function or anatomy may allow elemental mercury into the bloodstream and the peritoneal space. Systemic effects of massive oral intake of mercury have rarely been reported. In this paper, we are presenting the highest single oral intake of elemental mercury by a child aged 3 years. A Libyan boy aged 3 years ingested approximately 750 grams of elemental mercury and was still asymptomatic. The patient had no existing disease or abnormal gastrointestinal function or anatomy. The physical examination was normal. His serum mercury level was 91 µg/L (normal: <5 µg/L), and he showed no clinical manifestations. Exposure to mercury in children through different circumstances remains a likely occurrence.

Manganese intoxication: the cause of an inexplicable epileptic syndrome in a 3 year old child.

PubMed

Herrero Hernandez, Elena; Discalzi, Gianluigi; Dassi, Patrizia; Jarre, Laura; Pira, Enrico

2003-08-01

Excess manganese (Mn) can cause several neurotoxic effects, however only a few studies have reported epileptic syndromes related to manganese intoxication. We describe an epileptic syndrome due to manganese intoxication in a 3 year old male child. His blood manganese was elevated, but no other abnormal values or toxic substances were found in blood or urine. The electroencephalogram (EEG) showed a picture of progressive encephalopathy, while brain magnetic resonance was normal. The patient's conditions rapidly worsened to epileptic status despite the use of antiepileptic drugs. Chelating treatment with CaNa(2)EDTA was initiated to remove excess manganese and promptly succeeded in reverting epileptic symptoms. Concurrently, manganese blood levels and electroencephalogram progressively normalized. Thereafter it has been possible to discontinue antiepileptic treatment, and the patient remains in excellent conditions without any treatment.

An on-line modified least-mean-square algorithm for training neurofuzzy controllers.

PubMed

Tan, Woei Wan

2007-04-01

The problem hindering the use of data-driven modelling methods for training controllers on-line is the lack of control over the amount by which the plant is excited. As the operating schedule determines the information available on-line, the knowledge of the process may degrade if the setpoint remains constant for an extended period. This paper proposes an identification algorithm that alleviates "learning interference" by incorporating fuzzy theory into the normalized least-mean-square update rule. The ability of the proposed methodology to achieve faster learning is examined by employing the algorithm to train a neurofuzzy feedforward controller for controlling a liquid level process. Since the proposed identification strategy has similarities with the normalized least-mean-square update rule and the recursive least-square estimator, the on-line learning rates of these algorithms are also compared.

Sperm characteristics, antioxidant status and hormonal profile in rats treated with artemisinin.

PubMed

Farombi, E O; Adedara, I A; Abolaji, A O; Anamelechi, J P; Sangodele, J O

2014-10-01

The indiscriminate use, abuse and patients' noncompliance to normal prescription of artemisinin and its derivatives are a common practice during the treatment for drug-resistant malaria parasites in most developing countries. This study investigated the influence of artemisinin on the testicular and epididymal sperm antioxidant systems as well as on the plasma levels of hormones from the pituitary and thyroid components of the brain-pituitary-testicular axis. Oral exposure of rats to 0, 7 and 35 mg kg(-1) artemisinin for 7 days showed that the testicular antioxidant status at both therapeutic dose (7 mg kg(-1) ) and overdose (35 mg kg(-1) ), and the sperm antioxidant status at therapeutic dose of artemisinin remained unaffected compared with control. However, increased hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant decrease in glutathione peroxidase and glutathione-S-transferase activities as well as glutathione level in spermatozoon of rats administered with overdose of artemisinin. While plasma levels of all the hormones investigated remained unaffected, severe epididymal degeneration with concomitant decrease in sperm quantity and quality was observed in rats treated with overdose of artemisinin compared with control. Overall, induction of oxidative stress in the epididymis, but not in the testes, could cause reproductive deficits in individuals unduly undergoing artemisinin therapy. © 2013 Blackwell Verlag GmbH.

Targeting neurotensin as a potential novel approach for the treatment of autism.

PubMed

Ghanizadeh, Ahmad

2010-10-01

The pathophysiology of autism remains obscure. Recently, serum neurotensin levels in children with autistic disorder have been found to be higher than those of normal children. Neurotensin is known to intensify neuronal NMDA-mediated glutamate signaling, which may cause apoptosis in autism. Further, an imbalance of glutamate/GABAergic system in autism has been described. These observations lead to a postulate that neurotensin may accentuate the hyperglutaminergic state in autism, leading to apoptosis. Targeting neurotensin might be a possible novel approach for the treatment of autism.

Targeting neurotensin as a potential novel approach for the treatment of autism

PubMed Central

2010-01-01

The pathophysiology of autism remains obscure. Recently, serum neurotensin levels in children with autistic disorder have been found to be higher than those of normal children. Neurotensin is known to intensify neuronal NMDA-mediated glutamate signaling, which may cause apoptosis in autism. Further, an imbalance of glutamate/GABAergic system in autism has been described. These observations lead to a postulate that neurotensin may accentuate the hyperglutaminergic state in autism, leading to apoptosis. Targeting neurotensin might be a possible novel approach for the treatment of autism. PMID:20920308

Standardization of plasma vitellogenin level for surveying environmental estrogen pollution using the Japanese common goby Acanthogobius flavimanus.

PubMed

Song, Jing; Nagae, Masaki; Soyano, Kiyoshi

2018-07-01

Field surveys of the impact of environmental estrogen (EE) pollution in aquatic wildlife have been conducted using vitellogenin (VTG) as a biomarker to evaluate the influence of EE. However, a standard baseline of VTG level that can be used to evaluate EE pollution has not been fully determined. To the best of our knowledge, the present study is the first to determine the standard baseline VTG level for evaluating the biological effects of EE pollution using the Japanese common goby (Acanthogobius flavimanus) as the target model fish. Plasma VTG and estradiol-17β (E 2 ) levels associated with the reproductive cycle of wild goby inhabiting an unpolluted environment were measured. Mean plasma VTG and E 2 levels exhibited similar changes, increasing in the yolk vesicle stage and peaking in the tertiary yolk stage in females. However, plasma VTG and E 2 levels showed no significant changes in males, remaining at low levels throughout the reproductive cycle. The highest VTG levels in females and males were 1.6 mg ml -1 and 124.87 ng ml -1 , respectively. These results indicate that the baseline level (normal level) in males was approximately 130 ng ml -1 at most. We concluded that the threshold between normal and abnormal levels with a 10% risk rate was 150 ng ml -1 in the wild male goby. Plasma VTG levels in males captured from Nagasaki Harbor were higher than the threshold in each reproductive developmental stage, indicating the possibility of EE pollution at this site. The biological standard baseline for VTG established in this study is useful for assessing EE pollution in natural waters. Copyright © 2018 John Wiley & Sons, Ltd.

Reconstruction for chronic grade-II posterior cruciate ligament deficiency in Malaysian military personnel.

PubMed

Ahmad, Shahrulazua; Mahidon, Rafedon; Shukur, Mohammad Hassan; Hamdan, Amiruddin; Kasmin, Musa

2014-12-01

To evaluate the outcome of reconstruction for chronic grade-II posterior cruciate ligament (PCL) deficiency in Malaysian military personnel. Medical records of 16 male military personnel aged 25 to 41 years who underwent reconstruction for chronic grade-II PCL deficiency using the quadruple hamstrings tendon by a single surgeon were reviewed. The mean time from injury to surgery was 43.6 (range, 3-104) months. 10 patients had grade-I (n=4), grade-III (n=2), and grade-IV (n=4) lesions of the medial femoral condyles. Seven patients had medial (n=6) and lateral (n=1) meniscus tears. At the 2-year follow-up, patients were asked to complete a questionnaire consisting of the Lysholm score, Tegner activity level, and International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form. Posterior drawer test, KT-2000 arthrometer test for posterior translation of the tibia, and military health grade (MHG) were assessed by an independent assessor. At the 2-year follow-up, the mean Lysholm score was 83; the score was excellent in 2 patients, good in 9, fair in 4, and poor in one. The mean IKDC subjective score was 74. The median Tegner activity level increased from 5.5 to 6. The posterior drawer test of 11 patients improved to grade I and the remaining 5 remained at grade II. The mean posterior translation of the tibia was 2.4 mm postoperatively; the posterior translation was normal in 8 patients, nearly normal in 7, and abnormal (≥ 6 mm) in one. The MHG improved in 14 patients and remained unchanged in 2. The latter 2 patients had no chondral lesion or meniscus injury. The first one was 40 years old with a postoperative IKDC score of 55 and a Tegner activity level of 2. The second one was 34 years old with a postoperative IKDC score of 65 and posterior translation of the tibia of 6 mm. Surgical reconstruction for chronic grade-II PCL injury achieved satisfactory outcome and may be appropriate for military personnel.

Pressure effects on band structures in dense lithium

NASA Astrophysics Data System (ADS)

Goto, Naoyuki; Nagara, Hitose

2012-07-01

We studied the change of the band structures in some structures of Li predicted at high pressures, using GGA and GW calculations. The width of the 1s band coming from the 1s electron of Li shows broadening by the pressurization, which is the normal behavior of bands at high pressure. The width of the band just below the Fermi level decreases by the pressurization, which is an opposite behavior to the normal bands. The character of this narrowing band is mostly p-like with a little s-like portion. The band gaps in some structures are really observed even by the GGA calculations. The gaps by the GW calculations increase to about 1.5 times the GGA values. Generally the one-shot GW calculation (diagonal only calculations) gives more reliable values than the GGA, but it may fail to predict band gaps for the case where band dispersion shows complex crossing near the Fermi level. There remains some structures for which GW calculations with off-diagonal elements taken into account are needed to identify the phase to be metallic or semiconducting.

Functional central hypothyroidism in the elderly.

PubMed

Sell, Maren A; Schott, Matthias; Tharandt, Lutz; Cissewski, Klaus; Scherbaum, Werner A; Willenberg, Holger S

2008-06-01

Previous studies have shown that blood concentrations of free thyroxin and basal thyroid-stimulating hormone (TSH) decrease during adult life. Suggested mechanisms include reduced thyroid activity resulting from decreased serum TSH concentrations, impairment of peripheral 5'-deiodinase, and an increase in reverse 3,5,3'-triiodothyronine due to non-thyroidal illness. However, testing of pituitary reserves leads to contradictory results and has infrequently been evaluated in studies. We investigated whether the response of TSH to thyrotropin-releasing hormone (TRH) is preserved during aging. This was tested in a cohort of 387 subjects aged 13 to 100 years in whom thyroid disease was excluded by normal thyroid ultrasound, normal values for free thyroxin, free triiodothyronin, TSH, and negative thyroid peroxidase antibodies. Serum concentrations of free thyroxin remained almost unchanged, whereas free triiodothyronin and TSH levels were lower in older subjects. In addition, the TSH response to TRH was blunted in older subjects, especially in male individuals. There is evidence that the decreased thyroid hormone levels observed in aging are due to lower TSH concentrations, and that lower TSH concentrations may be linked to an impaired pituitary activity.

Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease.

PubMed

Soldan, Anja; Pettigrew, Corinne; Cai, Qing; Wang, Jiangxia; Wang, Mei-Cheng; Moghekar, Abhay; Miller, Michael I; Albert, Marilyn

2017-12-01

We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau, and neurodegeneration. Higher CR scores were associated with better cognitive performance but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI before symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Fossil insect evidence for the end of the Western Settlement in Norse Greenland

NASA Astrophysics Data System (ADS)

Panagiotakopulu, Eva; Skidmore, Peter; Buckland, Paul

2007-04-01

The fate of Norse farming settlements in southwest Greenland has often been seen as one of the great mysteries of North Atlantic colonization and expansion. Preservation of organic remains in the permafrost of the area of the Western Settlement, inland from the modern capital Nuuk, allowed very detailed study of the phases of occupation. Samples were taken from house floors and middens during the process of archaeological excavations and from insect remains were abstracted and identified in the laboratory. In this study, we present a new paleoecological approach principally examining the fossil fly faunas from house floors. The results of our study provide contrasting detailed pictures of the demise of two neighboring farms, Gården under Sandet and Nipaatsoq, one where abandonment appears as part of a normal process of site selection and desertion, and the other where the end was more traumatic. The level of detail, which was obtained by analysis of the dipterous (true fly) remains, exceeds all previous work and provides insights otherwise unobtainable.

Fossil insect evidence for the end of the Western Settlement in Norse Greenland.

PubMed

Panagiotakopulu, Eva; Skidmore, Peter; Buckland, Paul

2007-04-01

The fate of Norse farming settlements in southwest Greenland has often been seen as one of the great mysteries of North Atlantic colonization and expansion. Preservation of organic remains in the permafrost of the area of the Western Settlement, inland from the modern capital Nuuk, allowed very detailed study of the phases of occupation. Samples were taken from house floors and middens during the process of archaeological excavations and from insect remains were abstracted and identified in the laboratory. In this study, we present a new paleoecological approach principally examining the fossil fly faunas from house floors. The results of our study provide contrasting detailed pictures of the demise of two neighboring farms, Gården under Sandet and Nipaatsoq, one where abandonment appears as part of a normal process of site selection and desertion, and the other where the end was more traumatic. The level of detail, which was obtained by analysis of the dipterous (true fly) remains, exceeds all previous work and provides insights otherwise unobtainable.

Relationships between serum bilirubins and production and conjugation of bilirubin. Studies in Gilbert's syndrome, Crigler-Najjar disease, hemolytic disorders, and rat models.

PubMed

Muraca, M; Fevery, J; Blanckaert, N

1987-02-01

The pattern of serum bilirubins was determined in serum of humans and rats with unconjugated hyperbilirubinemia due to increased pigment load or defective hepatic conjugation. Bilirubin ester conjugates were present in all serum samples tested and were identified as bilirubin 1-O-acyl glucuronides. In Gilbert's syndrome, the concentration of total conjugates was comparable to the values in healthy control subjects. Because the concentration of unconjugated pigment was increased, the fraction of conjugated relative to total bilirubins was markedly decreased. Sera from patients with Crigler-Najjar disease differed from those with Gilbert's syndrome by the higher unconjugated bilirubin levels and the undetectability of diconjugated bilirubins. A striking finding was that in hemolytic disease, the concentration of both monoconjugates and diconjugates was enhanced in parallel with the increase of unconjugated pigment. Therefore, the fraction of conjugated relative to total bilirubins remained within the normal range. As in Gilbert's syndrome, heterozygote R/APfd-j/+ rats with impaired hepatic bilirubin conjugation exhibit an increased unconjugated bilirubin level in serum, whereas the concentration of total conjugates was comparable to the values in normal rats. In serum of normal rats loaded intraperitoneally with unconjugated bilirubin, both unconjugated and mono- and diconjugated bilirubins were increased in parallel so that the ratio of unconjugated to esterified pigment remained unaffected. Decreased hepatic conjugation or increased bilirubin load was associated with a lower percentage of diconjugates relative to total conjugates both in human and rat serum. The present results are consistent with a compartmental model in which there is bidirectional transfer across the sinusoidal membrane for unconjugated bilirubin as well as for the bilirubin glucuronides. Because typical patterns of serum bilirubins are found in Gilbert's syndrome and patients with hemolytic hyperbilirubinemia, determination of esterified bilirubins in serum is of value to study the pathophysiology and the differential diagnosis of unconjugated hyperbilirubinemia.

STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells.

PubMed

Liu, Yi; Luo, Fei; Wang, Bairu; Li, Huiqiao; Xu, Yuan; Liu, Xinlu; Shi, Le; Lu, Xiaolin; Xu, Wenchao; Lu, Lu; Qin, Yu; Xiang, Quanyong; Liu, Qizhan

2016-01-01

Although microRNA (miRNA) enclosed in exosomes can mediate intercellular communication, the roles of exosomal miRNA and angiogenesis in lung cancer remain unclear. We investigated functions of STAT3-regulated exosomal miR-21 derived from cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells in the angiogenesis of CSE-induced carcinogenesis. miR-21 levels in serum were higher in smokers than those in non-smokers. The medium from transformed HBE cells promoted miR-21 levels in normal HBE cells and angiogenesis of human umbilical vein endothelial cells (HUVEC). Transformed cells transferred miR-21 into normal HBE cells via exosomes. Knockdown of STAT3 reduced miR-21 levels in exosomes derived from transformed HBE cells, which blocked the angiogenesis. Exosomes derived from transformed HBE cells elevated levels of vascular endothelial growth factor (VEGF) in HBE cells and thereby promoted angiogenesis in HUVEC cells. Inhibition of exosomal miR-21, however, decreased VEGF levels in recipient cells, which blocked exosome-induced angiogenesis. Thus, miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of HBE cells. These results, demonstrating the function of exosomal miR-21 from transformed HBE cells, provide a new perspective for intervention strategies to prevent carcinogenesis of lung cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reduced m6A mRNA methylation is correlated with the progression of human cervical cancer

PubMed Central

Kong, Beihua; Song, Chen; Cong, Jianglin; Hou, Jianqing; Wang, Shaoguang

2017-01-01

The m6A mRNA methylation involves in mRNA splicing, degradation and translation. Recent studies have revealed that reduced m6A mRNA methylation might promote cancer development. However, the role of m6A mRNA methylation in cervical cancer development remains unknown. Therefore, we investigated the role of m6A methylation in cervical cancer in the current study. We first evaluated the m6A mRNA methylation level in 286 pairs of cervical cancer samples and their adjacent normal tissues by dot blot assay. Then the role of m6A on patient survival rates and cervical cancer progression were assessed. The m6A level was significantly reduced in the cervical cancer when comparing with the adjacent normal tissue. The m6A level reduction was significantly correlated with the FIGO stage, tumor size, differentiation, lymph invasion and cancer recurrence. It was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with cervical cancer. Reducing m6A level via manipulating the m6A regulators expression promoted cervical cancer cell proliferation. And increasing m6A level significantly suppressed tumor development both in vitro and in vivo. Our results showed that the reduced m6A level is tightly associated with cervical cancer development and m6A mRNA methylation might be a potential therapeutic target in cervical cancer. PMID:29228737

The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas

PubMed Central

Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

2016-01-01

Introduction Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. Aim The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. Materials and Methods This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn’t warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Results Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple’s procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Conclusion Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn’t predict vascular involvement and liver metastasis. PMID:27134925

The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas.

PubMed

Pandiaraja, Jayabal; Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

2016-03-01

Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn't warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple's procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn't predict vascular involvement and liver metastasis.

Seminar: Developmental Dyslexia

PubMed Central

Peterson, Robin L.; Pennington, Bruce F.

2012-01-01

Summary Dyslexia is a neurodevelopmental disorder that is characterized by slow and inaccurate word recognition. Dyslexia has been found in every culture studied, and mounting evidence underscores cross-linguistic similarity in its neurobiological and neurocognitive bases. There has been considerable progress across levels of analysis in the last five years. At a neuropsychological level, the phonological theory remains the most compelling, though it is increasingly clear that phonological problems interact with other cognitive risk factors. At a neurobiological level, recent research confirms that dyslexia is characterized by dysfunction of the normal left hemisphere language network and also implicates abnormal white matter development. Studies accounting for reading experience demonstrate that many observed neural differences reflect causes rather than effects of dyslexia. At an etiologic risk level, six candidate genes have been identified, and there is evidence for gene by environment interaction. This review includes a focus on these and other recent developments. PMID:22513218

Assessment of activity in Sarcoidosis. Sensitivity and specificity of 67Gallium scintigraphy, serum ACE levels, chest roentgenography, and blood lymphocyte subpopulations

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

Klech, H.; Kohn, H.; Kummer, F.

1982-12-01

The value of different factors are examined to assess activity in 60 patients with biopsy-proven sarcoidosis. In patients with active sarcoidosis (n . 35), /sup 67/Ga scans proved to be the most sensitive method (94 percent sensitivity), followed by serum angiotensin I converting enzyme (S-ACE) levels, chest x-ray films, and lymphocyte assays. In patients with peripheral pulmonary lesions, chest x-ray films failed in 32 percent of cases to document activity (68 percent sensitivity) whereas /sup 67/Ga scans and S-ACE levels remained to give reliable results. Despite poor specificity, negative /sup 67/Ga scans together with normal ACE levels have a highmore » predictive value for exclusion of active sarcoidosis. In patients with peripheral pulmonary lesions, chest roentgenography is of doubtful value for staging lung involvement and assessment of activity including monitoring and control of therapy.« less

Efficacy and safety of enzyme-replacement-therapy with agalsidase alfa in 36 treatment-naïve Fabry disease patients.

PubMed

Tsuboi, Kazuya; Yamamoto, Hiroshi

2017-06-07

Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the α-galactosidase A gene mutations. Enzyme-replacement-therapy (ERT) products for FD currently used include agalsidase alfa and agalsidase beta. There are many reports on efficacy and safety of ERT. However, most of the previous studies are done as a retrospective medical records analysis. The Japan Fabry Research - 002 (JFR-002) was a prospective observational clinical study of 36 ERT-naïve FD patients (14 men and 22 women) at baseline (BL) and after initiation of ERT with agalsidase alfa 0.2 mg/kg every two weeks, a median period 62.5 months. The parameters measured included globotriaosylceramide (Gb3), globotriaosylsphingosine (Lyso-Gb3), left ventricular mass index (LVMI), brain natriuretic peptide (BNP), high-sensitivity troponin I (hs-Trop I), estimated glomerular filtration rate (eGFR), and anti-agalsidase alfa IgG antibody formation. All parameters remained steady during ERT treatment period. BNP levels in 14 patients whose BL levels were within the normal range (<19.5 pg/mL) remained within the same range, while 22 patients whose BL levels were abnormally high (≥19.5 pg/mL) gradually showed decreased levels after start of ERT. Gb3 and Lyso-Gb3 levels remarkably decreased after the initiation of ERT and remained low. The JFR-002 suggests that agalsidase alfa is effective in maintaining organ function in FD patients, and that the incidence of infusion reactions related to the treatment with agalsidase alfa is low, indicating the good tolerability to this ERT. The JFR-002 was retrospectively registered at Japan Medical Association Center for Clinical Trials (Registration number: JMA-IIA00291 ) on May 19th, 2017.

Quantifying the behavioral response of spawning chum salmon to elevated discharges from Bonneville Dam, Columbia River, USA

USGS Publications Warehouse

Tiffan, K.F.; Haskell, C.A.; Kock, T.J.

2010-01-01

Chum salmon Oncorhynchus keta that spawn in main-stem habitats below Bonneville Dam on the Columbia River, USA, are periodically subjected to elevated discharges that may alter spawning behaviour. We investigated behavioural responses of spawning chum salmon to increased water velocities associated with experimental increases in tailwater elevation using acoustic telemetry and a dual-frequency identification sonar. Chum salmon primarily remained near their redds at base tailwater elevations (3.5 m above mean sea level), but displayed different movement and behavioural responses as elevations were increased to either 4.1 or 4.7m for 8-h periods. When velocities remained suitable (<0.8m s-1) during elevated-tailwater tests, female chum salmon remained near their redds but exhibited reduced digging activity as water velocities increased. However, when velocities exceeded 0.8m s-1, the females that remained on their redds exhibited increased swimming activity and digging virtually ceased. Female and male chum salmon that left their redds when velocities became unsuitable moved mean distances ranging from 32 to 58 m to occupy suitable velocities, but returned to their redds after tailwaters returned to base levels. Spawning events (i.e. egg deposition) were observed for five of nine pairs of chum salmon following tests indicating any disruptions to normal behaviour caused by elevated tailwaters were likely temporary. We believe a chum salmon's decision to either remain on, or leave, its redd during periods of unsuitably high water velocities reflects time invested in the redd and the associated energetic costs it is willing to incur. ?? 2009 John Wiley & Sons, Ltd.

Evidence that histamine is the causative toxin of scombroid-fish poisoning.

PubMed

Morrow, J D; Margolies, G R; Rowland, J; Roberts, L J

1991-03-14

The highest morbidity worldwide from fish poisoning results from the ingestion of spoiled scombroid fish, such as tuna and mackerel, and its cause is not clear. Histamine could be responsible, because spoiled scombroid fish contain large quantities of histamine. Whether histamine is the causative toxin, however, has remained in question. To address this issue, we investigated whether histamine homeostasis is altered in poisoned people. The urinary excretion of histamine and its metabolite, N-methylhistamine, was measured in three persons who had scombroid-fish poisoning (scombrotoxism) after the ingestion of marlin. We measured 9 alpha, 11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid (PGD-M), the principal metabolite of prostaglandin D2, a mast-cell secretory product, to assess whether mast cells had been activated to release histamine. The fish contained high levels of histamine (842 to 2503 mumol per 100 g of tissue). Symptoms of scombrotoxism--flushing and headache--began 10 to 30 minutes after the ingestion of fish. In urine samples collected one to four hours after fish ingestion, the levels of histamine and N-methylhistamine were 9 to 20 times and 15 to 20 times the normal mean, respectively. During the subsequent 24 hours, the levels fell to 4 to 15 times and 4 to 11 times the normal values. Levels of both were normal 14 days later. PGD-M excretion was not increased at any time. Two persons treated with diphenhydramine had prompt amelioration of symptoms. Scombroid-fish poisoning is associated with urinary excretion of histamine in quantities far exceeding those required to produce toxicity. The histamine is most likely derived from the spoiled fish. These results identify histamine as the toxin responsible for scombroid-fish poisoning.

Hyporeninemic hypoaldosteronism in a patient with diabetes mellitus: an unforgettable case report.

PubMed

Chelaghma, Naziha; Oyibo, Samson O

2018-01-01

A 58-year-old man presented with a 3-year history of chronic and intermittent hyperkalemia requiring recurrent attendances to the emergency department for urgent treatment. His medical history included secondary diabetes mellitus following a bout of acute pancreatitis and a previous splenectomy for a spontaneous splenic rupture. He also had a history of prolonged use of non-steroidal anti-inflammatory drugs for back pain and painful neuropathy. He was not on any medication or diet that would cause a raised serum potassium level and his renal function was normal. He was on a basal-bolus insulin regimen but his diabetes control had been poor for several years. As the hyperkalemia had gone on for so long in the presence of normal renal function, he went on to have further tests. Adrenal insufficiency had been ruled out following a short Synacthen test. Further investigations revealed low serum aldosterone levels and inappropriately low serum renin levels in the presence of hyperkalemia. This was suggestive of hyporeninemic hypoaldosteronism (HH). He was then treated with fludrocortisone and furosemide and his serum potassium levels remained normal. Additionally, he did not require any more emergency admissions to treat hyperkalemia thereafter. It was concluded that the HH-induced hyperkalemia was caused by diabetes mellitus or due to a combination of diabetes and prolonged use of non-steroidal anti-inflammatory drugs. The absence of renal impairment may have contributed to the delay in diagnosis. HH is a commonly overlooked cause of hyperkalemia. This case highlights the fact that it should always be suspected when unexplained hyperkalemia is found in patients with only mild-moderately impaired renal function, especially in the presence of diabetes mellitus.

Plasma progesterone levels and luteal activity during gestation and prolonged oviductal egg retention in a tropical lizard, Calotes versicolor.

PubMed

Shanbhag, B A; Radder, R S; Saidapur, S K

2001-07-01

Plasma progesterone (P) levels and luteal and adrenal activities were studied during normal gestation and unusual prolonged period of oviductal egg retention in a polyautochronic, multiclutched lizard, Calotes versicolor. The normal gestation period (approximately 15 days) was categorized into four stages: stage I--a few hours following ovulation, stage II--eggs with shell and embryo at primitive streak, stage III--embryonic stages 16-20, and stage IV--prior to ovipostion (stages 26-27). The gravid lizards maintained in captivity retained eggs in their oviducts for 45 days. Plasma P levels were low in stage I, increased significantly during stage II, declined in stage III, and reached their lowest in stage IV of gestation. 3Beta-hydroxysteroid dehydrogenase (3beta-HSDH) activity was greater in lutein cells at stage II and was present in traces in stage IV gestation. Interestingly, plasma P titers that were high in lizards with eggs retained longer though the corpora lutea (CL) showed a trace 3beta-HSDH activity. However, 3beta-HSDH activity was greater in the adrenocortical cells in these lizards than that in lizards during a normal gestation period. The present study on C. versicolor shows that the CL remains active and secretes P only during the early part of the gestation. The drop in P level during the later part of gestation might facilitate growth of a second set of vitellogenic follicles. During unfavorable conditions when the lizards are forced to retain eggs in the oviduct, the adrenal glands seem to secrete progesterone to help in egg retention and in inhibition of oviposition.

Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

PubMed Central

Anderson, W P; Johnston, C I; Korner, P I

1979-01-01

1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

The influence of body position and microclimate on ketamine and metabolite distribution in decomposed skeletal remains.

PubMed

Cornthwaite, H M; Watterson, J H

2014-10-01

The influence of body position and microclimate on ketamine (KET) and metabolite distribution in decomposed bone tissue was examined. Rats received 75 mg/kg (i.p.) KET (n = 30) or remained drug-free (controls, n = 4). Following euthanasia, rats were divided into two groups and placed outdoors to decompose in one of the three positions: supine (SUP), prone (PRO) or upright (UPR). One group decomposed in a shaded, wooded microclimate (Site 1) while the other decomposed in an exposed sunlit microclimate with gravel substrate (Site 2), roughly 500 m from Site 1. Following decomposition, bones (lumbar vertebrae, thoracic vertebra, cervical vertebrae, rib, pelvis, femora, tibiae, humeri and scapulae) were collected and sorted for analysis. Clean, ground bones underwent microwave-assisted extraction using acetone : hexane mixture (1 : 1, v/v), followed by solid-phase extraction and analysis using GC-MS. Drug levels, expressed as mass normalized response ratios, were compared across all bone types between body position and microclimates. Bone type was a main effect (P < 0.05) for drug level and drug/metabolite level ratio for all body positions and microclimates examined. Microclimate and body position significantly influenced observed drug levels: higher levels were observed in carcasses decomposing in direct sunlight, where reduced entomological activity led to slowed decomposition. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Empirical Research on Ecological Development Level of Resource-based Industries-Base on the data of the Silk Road Economic Belt Core Zone

NASA Astrophysics Data System (ADS)

Wang, Lei; Yan, Min

2017-11-01

Industrial ecology is the epitome of sustainable development in industry level, is one effective gateway to realizing green transformation. On the basis of industrial ecology development, including resource efficiency and environmental efficiency of ecological evaluation index system, this paper evaluates the level of industrial ecology development of resource-based industries in Xinjiang using entropy method. Research shows that the overall ecological development level of resource-based industries has remained at continuous improved trend with slow improvement in resource efficiency, and relative faster improvement in environmental efficiency. With economic development entering into the period of new normal at the end of the “twelfth five year plan”, the resource efficiency of ecological development of resource-based industries demonstrated a downward trend. The overall level of industrial ecology also faced with certain fluctuations, various ecological development level of resource-based industries also presented a downward trend. To promote ecological development of resource-based industries in Xinjiang, countermeasures and suggestions are initiated.

Identity: empirical contribution. Changes in the identity integration of adolescents in treatment for personality disorders.

PubMed

Feenstra, Dine J; Hutsebaut, Joost; Verheul, Roel; van Limbeek, Jacques

2014-02-01

A renewed interest in identity as one of the core markers of personality disorders has been introduced by the DSM-5 Level of Personality Functioning Scale. However, little is known about the utility of the construct of identity in children and adolescents. This study aimed to broaden the knowledge of identity integration as a core component of personality functioning in adolescents. The authors investigated levels of identity integration, as measured by the Severity Indices of Personality Problems (SIPP-118; Verheul et al., 2008), in adolescents in both normal (n = 406) and clinical populations (n = 285). Furthermore, changes in levels of identity integration during treatment were investigated in a clinical subsample (n = 76). Levels of identity integration were not associated with age. They were, however, associated with the absence or presence of personality pathology. Most adolescents receiving inpatient psychotherapy gradually changed toward more healthy levels of identity integration; a significant number, however, remained at maladaptive levels of identity functioning after intensive psychotherapy.

suPAR level is associated with myocardial impairment assessed with advanced echocardiography in patients with type 1 diabetes with normal ejection fraction and without known heart disease or end-stage renal disease.

PubMed

Theilade, Simone; Rossing, Peter; Eugen-Olsen, Jesper; Jensen, Jan S; Jensen, Magnus T

2016-06-01

Heart disease is a common fatal diabetes-related complication. Early detection of patients at particular risk of heart disease is of prime importance. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker for development of cardiovascular disease. We investigate if suPAR is associated with early myocardial impairment assessed with advanced echocardiographic methods. In an observational study on 318 patients with type 1 diabetes without known heart disease and with normal left ventricular ejection fraction (LVEF) (biplane LVEF >45%), we performed conventional, tissue Doppler and speckle tracking echocardiography, and measured plasma suPAR levels. Associations between myocardial function and suPAR levels were studied in adjusted models including significant covariates. Patients were 55±12 years (mean±s.d.) and 160 (50%) males. Median (interquartile range) suPAR was 3.4 (1.7) ng/mL and LVEF was 58±5%. suPAR levels were not associated with LVEF (P=0.11). In adjusted models, higher suPAR levels were independently associated with both impaired systolic function assessed with global longitudinal strain (GLS) and tissue velocity s', and with impaired diastolic measures a' and e'/a' (all P=0.034). In multivariable analysis including cardiovascular risk factors and both systolic and diastolic measures (GLS and e'/a'), both remained independently associated with suPAR levels (P=0.012). In patients with type 1 diabetes with normal LVEF and without known heart disease, suPAR is associated with early systolic and diastolic myocardial impairment. Our study implies that both suPAR and advanced echocardiography are useful diagnostic tools for identifying patients with diabetes at risk of future clinical heart disease, suited for intensified medical therapy. © 2016 European Society of Endocrinology.

Role of endogenous cortistatin in the regulation of ghrelin system expression at pancreatic level under normal and obese conditions.

PubMed

Chanclón, Belén; Luque, Raúl M; Córdoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; Castaño, Justo P; Gracia-Navarro, Francisco; Martínez-Fuentes, Antonio J

2013-01-01

Ghrelin-system components [native ghrelin, In1-ghrelin, Ghrelin-O-acyltransferase enzyme (GOAT) and receptors (GHS-Rs)] are expressed in a wide variety of tissues, including the pancreas, where they exert different biological actions including regulation of neuroendocrine secretions, food intake and pancreatic function. The expression of ghrelin system is regulated by metabolic conditions (fasting/obesity) and is associated with the progression of obesity and insulin resistance. Cortistatin (CORT), a neuropeptide able to activate GHS-R, has emerged as an additional link in gut-brain interplay. Indeed, we recently reported that male CORT deficient mice (cort-/-) are insulin-resistant and present a clear dysregulation in the stomach ghrelin-system. The present work was focused at analyzing the expression pattern of ghrelin-system components at pancreas level in cort-/- mice and their control littermates (cort +/+) under low- or high-fat diet. Our data reveal that all the ghrelin-system components are expressed at the mouse pancreatic level, where, interestingly, In1-ghrelin was expressed at higher levels than native-ghrelin. Thus, GOAT mRNA levels were significantly lower in cort-/- mice compared with controls while native ghrelin, In1-ghrelin and GHS-R transcript levels remained unaltered under normal metabolic conditions. Moreover, under obese condition, a significant increase in pancreatic expression of native-ghrelin, In1-ghrelin and GHS-R was observed in obese cort+/+ but not in cort-/- mice. Interestingly, insulin expression and release was elevated in obese cort+/+, while these changes were not observed in obese cort-/- mice. Altogether, our results indicate that the ghrelin-system expression is clearly regulated in the pancreas of cort+/+ and cort -/- under normal and/or obesity conditions suggesting that this system may play relevant roles in the endocrine pancreas. Most importantly, our data demonstrate, for the first time, that endogenous CORT is essential for the obesity-induced changes in insulin expression/secretion observed in mice, suggesting that CORT is a key regulatory component of the pancreatic function.

Exertional Rhabdomyolysis in a Collegiate American Football Player After Preventive Cold-Water Immersion: A Case Report

PubMed Central

Kahanov, Leamor; Eberman, Lindsey E.; Wasik, Mitchell; Alvey, Thurman

2012-01-01

Objective: To describe a case of exertional rhabdomyolysis in a collegiate American football player after preventive cold-water immersion. Background: A healthy man (19 years old) participated in full-contact football practice followed by conditioning (2.5 hours). After practice, he entered a coach-mandated post-practice cold-water immersion and had no signs of heat illness before developing leg cramps, for which he presented to the athletic training staff. After 10 minutes of repeated stretching, massage, and replacement of electrolyte-filled fluids, he was transported to the emergency room. Laboratory tests indicated a creatine kinase (CK) level of 2545 IU/L (normal range, 45–260 IU/L), CK-myoglobin fraction of 8.5 ng/mL (normal < 6.7 ng/mL), and CK-myoglobin relative index of 30% (normal range, 25%– 30%). Myoglobin was measured at 499 ng/mL (normal = 80 ng/mL). The attending physician treated the athlete with intravenous fluids. Differential Diagnosis: Exercise-associated muscle cramps, dehydration, exertional rhabdomyolysis. Treatment: The patient was treated with rest and rehydration. One week after the incident, he began biking and swimming. Eighteen days later, the patient continued to demonstrate elevated CK levels (527 IU/L) but described no other symptoms and was allowed to return to football practice as tolerated. Two months after the incident, his CK level remained high (1900 IU/L). Uniqueness: The athlete demonstrated no signs of heat illness upon entering the cold-water immersion but experienced severe leg cramping after immersion, resulting in a diagnosis of exertional rhabdomyolysis. Previously described cases have not linked cold-water immersion with the pathogenesis of rhabdomyolysis. Conclusions: In this football player, CK levels appeared to be a poor indicator of rhabdomyolysis. Our patient demonstrated no other signs of the illness weeks after the incident, yet his elevated CK levels persisted. Cold-water immersion immediately after exercise should be monitored by the athletic training staff and may not be appropriate to prevent muscle damage, given the lack of supporting evidence. PMID:22488291

Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion

PubMed Central

Ortega‐Sáenz, Patricia; Macías, David; Levitsky, Konstantin L.; Rodríguez‐Gómez, José A.; González‐Rodríguez, Patricia; Bonilla‐Henao, Victoria; Arias‐Mayenco, Ignacio

2016-01-01

Key points Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB).In biotin‐deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin.Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis. Remarkably, glomus cells from these animals have normal electrical and neurochemical properties. However, they show a marked decrease in the size of quantal dopaminergic secretory events.Inhibitors of the vesicular monoamine transporter 2 (VMAT2) mimic the effect of biotin deficiency. In biotin‐deficient animals, VMAT2 protein expression decreases in parallel with biotin depletion in CB cells.These data suggest that dopamine transport and/or storage in small secretory granules in glomus cells depend on biotin. Abstract Biotin is a water‐soluble vitamin required for the function of carboxylases as well as for the regulation of gene expression. Here, we report that biotin accumulates in unusually large amounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). We show in a biotin‐deficient rat model that the vitamin rapidly disappears from the blood and other tissues (including the AM), while remaining at relatively high levels in the CB. We have also observed that, in comparison with other peripheral neural tissues, CB cells contain high levels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Biotin‐deficient rats show a syndrome characterized by marked weight loss, metabolic lactic acidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably, CB cells from biotin‐deficient animals have normal electrophysiological and neurochemical (ATP levels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the size of quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differential secretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor of the vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (in comparison with VMAT1), and in biotin‐deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotin has an essential role in the homeostasis of dopaminergic transmission modulating the transport and/or storage of transmitters within small secretory granules in glomus cells. PMID:27570189

Quality of Clotting Factor Activity in Fresh Frozen Plasma at Thaw with a Microwave System and after Storage at 4 degrees C for 48 Hours.

PubMed

Kuta, Piotr; Hauck-Dlimi, Barbara; Strobel, Julian; Zimmermann, Robert; Eckstein, Reinhold

2016-01-01

Uncontrolled hemorrhage in polytrauma patients usually results in rapid need of blood products. Despite the shorter thawing times of microwave devices for heating fresh frozen plasma (FFP), their use has remained controversial, and just a few laboratory analyses have been published on this topic. The aim of this study was to analyse the quality of clotting factors immediately after thawing FFP with a microwave device and after 48-hour post thaw storage at 4 degrees C. 24 FFP units of all four ABO blood groups (six of each blood group) were thawed with a Transfusio-therm 2000 and later stored at 4 degrees C for 48 hours. Samples were drawn aseptically and investigated on various clotting factors and protein proteases (fibrinogen, antithrombin, FII, FV, FVII, FVIII, FIX, FX, FXI, FXIII, vWF antigen and activity, protein S, and protein C) using standard coagulation and chromogenic assays immediately after thawing and again after a 48-hour storage period at 4 degrees C. All units were tested for both anaerobic and aerobic microbial contamination using standard operating procedures immediately after thawing. After thawing, all coagulation factors and protein protease activities were within normal ranges. Blood group O individuals had approximately 25% lower plasma levels of vWF antigen and activity. After a 48-hour storage period at 4 degrees C, FVIII and FIX activities declined significantly in all blood groups, whereas the remaining clotting factors remained comparably stable. Immediately after rapid thawing using a microwave system, all FFP units contained adequate coagulation factor activities to maintain hemostatic activity at the time of product thaw. The post thaw refrigerated storage caused an anticipated decrease in factor VIII and IX activities, but retained normal coagulation factor levels of many plasma proteins. Therefore we conclude that the Transfusio-therm 2000 has no clinically significant influence on the activity of clotting factors and plasma proteases in FFP units.

THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS

PubMed Central

Hirsch, Robert L.; Kellner, Aaron

1956-01-01

Rabbits subjected to subtotal hepatectomy failed to develop increased serum cholesterol levels following parenteral injection of triton WR 1339, the finding indicating that the liver is essential for the establishment of the hypercholesterolemia induced by surface-active agents. The cholesterol content of the livers of rabbits rendered hyperlipemic by means of triton remained unchanged both during the rapid rise of the serum cholesterol levels and during the return to normal values. By contrast, the cholesterol content of the livers of rabbits fed cholesterol rose progressively over a period of 5 weeks, concommittant with the increase in serum cholesterol levels. The findings provide support for the hypothesis that surface-active agents bring about hyperlipemia by altering the circulating lipoproteins in some manner so that they are retained in the circulating body fluids. PMID:13332177

HIV models for treatment interruption: Adaptation and comparison

NASA Astrophysics Data System (ADS)

Hillmann, Andreas; Crane, Martin; Ruskin, Heather J.

2017-10-01

In recent years, Antiretroviral Therapy (ART) has become commonplace for treating HIV infections, although a cure remains elusive, given reservoirs of replicating latently-infected cells, which are resistant to normal treatment regimes. Treatment interruptions, whether ad hoc or structured, are known to cause a rapid increase in viral production to detectable levels, but numerous clinical trials remain inconclusive on the dangers inherent in this resurgence. In consequence, interest in examining interruption strategies has recently been rekindled. This overview considers modelling approaches, which have been used to explore the issue of treatment interruption. We highlight their purpose and the formalisms employed and examine ways in which clinical data have been used. Implementation of selected models is demonstrated, illustrative examples provided and model performance compared for these cases. Possible extensions to bottom-up modelling techniques for treatment interruptions are briefly discussed.

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

PubMed

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.

Validation of OMI Measured Radiances Over Ice

NASA Astrophysics Data System (ADS)

Jaross, G.; Cebula, R. P.; Warner, J.

2005-12-01

The Ozone Monitoring Instrument (OMI) was launched aboard the EOS Aura satellite on 15 July, 2004 and has since performed quite well. Calibrated radiances in the form of Level 1 data products are produced regularly every orbit with minimal data loss. A total of 12 atmospheric constituent data products are currently planned for the OMI science data processing. All rely, to varying degrees, on the sun-normalized radiances of the OMI sensor. Retrievals of atmospheric trace constituents, such as NO{}_2, BrO, OCLO, and HCHO, rely upon spectroscopy and tend to be insensitive to errors in the absolute radiance levels. But column O{}_3 amount, aerosol properties, cloud heights, and UV surface radiation have significant sensitivities to changes in the sun-normalized radiances. In this presentation we discuss our evaluation of the OMI sun-normalized radiances between 330 nm and 500 nm. This covers most of the OMI spectral range where ozone absorption is small. Our technique involves a comparison of normalized radiances measured by OMI over the Antarctic continent with top-of-the-atmosphere (TOA) values computed with a radiative transfer model. In our model we assume a Rayleigh-scattering, aerosol-free, cloud-free atmosphere, and a mean surface reflectance derived from measurements on the ground. TOA radiances are sensitive to the bi-directional distribution of surface reflectance, especially at high solar zenith angles. We have developed a surface reflectance model to help correct these effects, but it still remains the largest source of uncertainty. We estimate the residual uncertainty at all wavelengths to be 2%.

Effect of tibial plateau leveling osteotomy on femorotibial contact mechanics and stifle kinematics.

PubMed

Kim, Stanley E; Pozzi, Antonio; Banks, Scott A; Conrad, Bryan P; Lewis, Daniel D

2009-01-01

To evaluate the effects of tibial plateau leveling osteotomy (TPLO) on femorotibial contact mechanics and 3-dimensional (3D) kinematics in cranial cruciate ligament (CrCL)-deficient stifles of dogs. In vitro biomechanical study. Unpaired pelvic limbs from 8 dogs, weighing 28-35 kg. Digital pressure sensors placed subjacent to the menisci were used to measure femorotibial contact force, contact area, peak and mean contact pressure, and peak pressure location with the limb under an axial load of 30% body weight and a stifle angle of 135 degrees. Three-dimensional static poses of the stifle were obtained using a Microscribe digitizing arm. Each specimen was tested under normal, CrCL-deficient, and TPLO-treated conditions. Repeated measures analysis of variance with a Tukey post hoc test (P<.05) was used for statistical comparison. Significant disturbances to all measured contact mechanical variables were evident after CrCL transection, which corresponded to marked cranial tibial subluxation and increased internal tibial rotation in the CrCL-deficient stifle. No significant differences in 3D femorotibial alignment were observed between normal and TPLO-treated stifles; however, femorotibial contact area remained significantly smaller and peak contact pressures in both medial and lateral stifle compartments were positioned more caudally on the tibial plateau, when compared with normal. Whereas TPLO eliminates craniocaudal stifle instability during simulated weight bearing, the procedure fails to concurrently restore femorotibial contact mechanics to normal. Progression of stifle osteoarthritis in dogs treated with TPLO may be partly the result of abnormal stifle contact mechanics induced by altering the orientation of the proximal tibial articulating surface.

The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women.

PubMed

Sinha-Hikim, I; Arver, S; Beall, G; Shen, R; Guerrero, M; Sattler, F; Shikuma, C; Nelson, J C; Landgren, B M; Mazer, N A; Bhasin, S

1998-04-01

Measurements of total and free testosterone levels in women have lacked precision and accuracy because of limited assay sensitivity. The paucity of normative data on total and free testosterone levels in healthy women has confounded interpretation of androgen levels in women with human immunodeficiency virus (HIV) infection and other disease states. Therefore, the objectives of this study were to develop sensitive assays for the measurement of the low total and free testosterone levels in women to define the range for these hormones during the normal menstrual cycle and assess the total and free testosterone levels in HIV-infected women. By using a larger volume of serum, increasing the incubation time, and reducing the antibody concentration, the sensitivity of the total testosterone assay was increased to 0.008 nmol/L, and that of the free testosterone assay was increased to 2 pmol/L. The mean percent free testosterone was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone levels in the follicular and luteal phases were not significantly different, but both demonstrated a modest preovulatory increase, 3 days before the LH peak. Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0 ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80) vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and free testosterone levels were also significantly lower in HIV-infected women who were menstruating normally. There were no significant differences in serum total and free testosterone levels between those who had lost weight and those who had not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid copy number. Serum FSH, but not LH, levels were significantly higher in HIV-infected women than in controls. Using assays with sufficient sensitivity, we defined the range for total and free testosterone levels during the normal menstrual cycle. Serum total and free testosterone levels are lower in HIV-infected women and correlate inversely with plasma HIV ribonucleic acid levels. The hypothesis that androgen deficiency contributes to wasting in HIV-infected women remains to be tested.

Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission

PubMed Central

Bonaventure, Pascal; Aluisio, Leah; Shoblock, James; Boggs, Jamin D.; Fraser, Ian C.; Lord, Brian; Lovenberg, Timothy W.; Galici, Ruggero

2011-01-01

The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission. PMID:21701689

Micro-spatial distribution of malaria cases and control strategies at ward level in Gwanda district, Matabeleland South, Zimbabwe.

PubMed

Manyangadze, Tawanda; Chimbari, Moses J; Macherera, Margaret; Mukaratirwa, Samson

2017-11-21

Although there has been a decline in the number of malaria cases in Zimbabwe since 2010, the disease remains the biggest public health threat in the country. Gwanda district, located in Matabeleland South Province of Zimbabwe has progressed to the malaria pre-elimination phase. The aim of this study was to determine the spatial distribution of malaria incidence at ward level for improving the planning and implementation of malaria elimination in the district. The Poisson purely spatial model was used to detect malaria clusters and their properties, including relative risk and significance levels at ward level. The geographically weighted Poisson regression (GWPR) model was used to explore the potential role and significance of environmental variables [rainfall, minimum and maximum temperature, altitude, Enhanced Vegetation Index (EVI), Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), rural/urban] and malaria control strategies [indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs)] on the spatial patterns of malaria incidence at ward level. Two significant clusters (p < 0.05) of malaria cases were identified: (1) ward 24 south of Gwanda district and (2) ward 9 in the urban municipality, with relative risks of 5.583 and 4.316, respectively. The semiparametric-GWPR model with both local and global variables had higher performance based on AICc (70.882) compared to global regression (74.390) and GWPR which assumed that all variables varied locally (73.364). The semiparametric-GWPR captured the spatially non-stationary relationship between malaria cases and minimum temperature, NDVI, NDWI, and altitude at the ward level. The influence of LLINs, IRS and rural or urban did not vary and remained in the model as global terms. NDWI (positive coefficients) and NDVI (range from negative to positive coefficients) showed significant association with malaria cases in some of the wards. The IRS had a protection effect on malaria incidence as expected. Malaria incidence is heterogeneous even in low-transmission zones including those in pre-elimination phase. The relationship between malaria cases and NDWI, NDVI, altitude, and minimum temperature may vary at local level. The results of this study can be used in planning and implementation of malaria control strategies at district and ward levels.

Effects of Increased CO2 Level on the Well-Being, Growth and Renal Function of Rats

NASA Technical Reports Server (NTRS)

Lang, C.; Bonner, R.; Vasques, M.; Baer, L.; Fung, P.; Steele, M.; Wade, C.

1994-01-01

On the Space Shuttle the mean CO2 levels have been 0.3% which is ten times normal air, while there have been extended periods with mean levels of 0.7% and peak concentrations of 2%. On the Space Station the projected mean concentration of CO2 is 0.7% and not to exceed 1.0%. To ensure that high level of CO2 does not compromise the integrity of the science on the Space Station, the effects of chronic exposure to high levels of CO2 were investigated. Following 7 days of cage adaptation animals exposed to 2% CO2 for 30 days were compared to control (ambient air) animals and the effects on the well-being, growth and renal function analyzed. Ten male rats per group were placed in individual metabolic cages which allowed monitoring of daily food and water consumption, as well as feces and urine to be collected. Cages were placed in a plexiglass chamber with internal environment controlled by a computer in conjunction with gas sensors. The elevated CO2 was held constant at 2.0 +/- 0.03% and the O2 at 20.9 +/- 0.15%. Body weight and food and water intake were measured daily for the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH, CO2 (as an indicator for bicarbonate) and ammonia (as an indicator for ammonium). During 2% CO2 exposure, animal growth, weight, food and water consumption were within normal ranges suggesting that their well-being was not affected. Urine pH decreased from 7.12 to 6.77 over the first 6 days of exposure and increased the following 24 days returning to pre-exposure levels. Urine NH4+ increased 68% the first 6 days then dropped to and remained at 29% higher than pre-exposure level. Urine bicarbonate concentration did not change the first 6 days, but significantly increased by day 30. These results of chronic exposure to 2% C02 are consistent with renal compensation for respiratory acidosis which may impact science conducted on the Space Shuttle or the Space Station if CO2 levels reach 2%.

Identification of a Secondary Promoter within the Human B Cell Receptor Component Gene hCD79b*

PubMed Central

Yoo, Eung Jae; Cooke, Nancy E.; Liebhaber, Stephen A.

2013-01-01

The human B cell-specific protein, CD79b (also known as Igβ and B29) constitutes an essential signal transduction component of the B cell receptor. Although its function is central to the triggering of B cell terminal differentiation in response to antigen stimulation, the transcriptional determinants that control CD79b gene expression remain poorly defined. In the present study, we explored these determinants using a series of hCD79b transgenic mouse models. Remarkably, we observed that the previously described hCD79b promoter along with its associated enhancer elements and first exon could be deleted without appreciable loss of hCD79b transcriptional activity or tissue specificity. In this deletion setting, a secondary promoter located within exon 2 maintained full levels and specificity of hCD79b transcription. Of note, this secondary promoter was also active, albeit at lower levels, in the wild-type hCD79b locus. The activity of the secondary promoter was dependent on the action(s) of a conserved sequence element mapping to a chromatin DNase I hypersensitive site located within intron 1. mRNA generated from this secondary promoter is predicted to encode an Igβ protein lacking a signal sequence and thus unable to serve normal B cell receptor function. Although the physiologic role of the hCD79b secondary promoter and its encoded protein remain unclear, the current data suggest that it has the capacity to play a role in normal as well as pathologic states in B cell proliferation and function. PMID:23649625

Neutrophil alveolitis following endotoxemia. Enhancement by previous exposure to hyperoxia.

PubMed

Rinaldo, J E; Dauber, J H; Christman, J; Rogers, R M

1984-12-01

We injected Escherichia coli endotoxin, 2.5 mg/kg, intraperitoneally in rats, sequentially quantified alveolar inflammation during a 6-day period by several techniques, and observed the effect of previous exposure to hyperoxia on the intensity of alveolitis in this model. As noted in other models of endotoxemia, we found intravascular sequestration of leukocytes and an increase in the retention of 125I albumin in the lung 4 to 6 h after the injection of endotoxin. Bronchoalveolar lavage fluid (BALF) obtained at this time only slightly stimulated the migration of neutrophils in vitro, and the numbers and types of cells recovered by lavage were normal. Fifteen h after the injection of endotoxin, however, bronchoalveolar lavage fluid stimulated both random and directed migration of neutrophils in vitro, although recovery of neutrophils by lavage was increased only slightly. By 24 h, 125I albumin retention had returned to normal levels, but the chemotactic activity of BALF remained high, and the percentage and absolute number of neutrophils recovered by lung lavage were increased markedly. The recovery of neutrophils remained significantly elevated for 3 days but declined to control levels by 6 days, whereas the recovery of alveolar macrophages was increased at this time. Exposure to 100% O2 for 36 h prior to endotoxemia accelerated and intensified neutrophil influx into the lung and increased the stimulatory effect of BALF on neutrophil migration in vitro. We conclude that a single episode of endotoxemia in the rat causes a multi-phasic alveolar inflammatory response, and that this response is accelerated and intensified by prior, mild exposure to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats

PubMed Central

Maurya, Brajesh Kumar; Trigun, Surendra Kumar

2016-01-01

Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1) induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC) induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase) level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis. PMID:26682000

[The effects of normal aging on face naming and recognition of famous people: battery 75].

PubMed

Pluchon, C; Simonnet, E; Toullat, G; Gil, R

2002-07-01

The difficulty to recall proper nouns is often something elderly people complain about. Thus, we tried to build and standardize a tool that could allow a quantified estimation of the naming and recognition abilities about famous people faces, specifying the part of gender, age and cultural level for each kind of test. The performances of 542 subjects divided in 3 age brackets and 3 academic knowledge levels were analysed. To carry out the test material, the artistic team of the Grevin Museum (Paris) was called upon. Their work offers a homogeneous way to shape famous people faces. One same person thus photographed 75 characters from different social categories with the same conditions of light, during only one day. The results of the study show that men perform better than women as concerns naming task, but that there's no difference between genders as concerns recognition task. Recognition performances are significantly better whatever the age, the gender and the cultural level may be. Generally, performances are all the more better since subjects are younger and have a higher cultural level. Our study then confirms the fact that normal aging goes hand in hand with rising difficulties to name faces. Moreover, results tend to show that recognition of faces remains better preserved and that the greater disability to recall a name is linked to difficulties in lexical accessing.

miR-133 involves in lung adenocarcinoma cell metastasis by targeting FLOT2.

PubMed

Wei, Guangxia; Xu, Yahuan; Peng, Tao; Yan, Jie

2018-03-01

Dysregulated microRNAs (miRNAs) reported to involve into the oncogenesis and progression in various human cancers. However, the roles and mechanism of miR-133 in lung adenocarcinoma remain largely unclear. In this study, qPCR assay and western blot were used to detect the expression levels of miR-133, Akt and FLOT2. Luciferase reporter assay was used to identify the target role of miR-133 on FLOT2. The cell invasion and the migration capability were performed using the transwell invasion assay and wound healing assay. We found that miR-133 expression levels were downregulated in human lung adenocarcinoma specimens and cell lines compared with the adjacent normal tissues and normal human bronchial epithelial cell. miR-133 significantly suppressed metastasis of lung adenocarcinoma cells in vitro. Furthermore, FLOT2 (flotillin-2) identified as a direct target of miR-133, and FLOT2 expression levels were inversely correlated with miR-133 expression levels in human lung adenocarcinoma specimens. And the restoration studies suggested FGF2 as a downstream effector of miR-133 which acted through Akt signalling pathway. Our study revealed the mechanism that miR-133 suppresses lung adenocarcinoma metastasis by targeting FLOT2 via Akt signalling pathway, implicating a potential prognostic biomarker and therapeutic target for lung adenocarcinoma treatment.

NHERF1, a novel GPER associated protein, increases stability and activation of GPER in ER-positive breast cancer

PubMed Central

Xiong, Ying; Wang, Yan; Zheng, Junfang; Zhao, Yuan; Tao, Tao; Wang, Qiqi; Liu, Hua; Wang, Songlin; Jiang, Wen G.; He, Junqi

2016-01-01

G protein-coupled estrogen receptor (GPER) plays an important role in mediating the effects of estradiol. High levels of GPER have been implicated to associate with the malignant progress of invasive breast cancer (IBC). However, the mechanisms by which GPER protein levels were regulated remain unclear. In this study, PDZ protein Na+/H+ exchanger regulatory factor (NHERF1) was found to interact with GPER in breast cancer cells. This interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal PDZ binding motif of GPER. NHERF1 was demonstrated to facilitate GPER expression at post-transcriptional level and improve GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in a GPER/NHERF1 interaction-dependent manner. In addition, GPER protein levels are positively associated with NHERF1 protein levels in a panel of estrogen receptor (ER)-positive breast cancer cells. Furthermore, analysis of clinical IBC data from The Cancer Genome Atlas (TCGA) showed no significant difference in GPER mRNA levels between ER-positive IBC and normal breast tissues. However, gene set enrichment analysis (GSEA) showed that GPER signaling is ultra-activated in ER-positive IBC when compared with normal and its activation is positively associated with NHERF1 mRNA levels. Taken together, our findings identify NHERF1 as a new binding partner for GPER and its overexpression promotes protein stability and activation of GPER in ER-positive IBC. Our data indicate that regulation of GPER stability by NHERF1 may contribute to GPER-mediated carcinogenesis in ER-positive IBC. PMID:27448983

ERBB3: A potential serum biomarker for early detection and therapeutic target for devil facial tumour 1 (DFT1)

PubMed Central

Kunde, Dale A.; Taylor, Robyn L.; Pyecroft, Stephen B.; Sohal, Sukhwinder Singh; Snow, Elizabeth T.

2017-01-01

Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1’s cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored. Under the hypothesis that serum ERBB3 levels may increase as DFT1 invades local and distant tissues our pilot study determined serum ERBB3 levels in normal Tasmanian devils and Tasmanian devils with DFT1. Compared to the baseline serum ERBB3 levels in unaffected Tasmanian devils, Tasmanian devils with DFT1 showed significant elevation of serum ERBB3 levels. Interestingly Tasmanian devils with cutaneous lymphoma (CL) also showed elevation of serum ERBB3 levels when compared to the baseline serum levels of Tasmanian devils without DFT1. Thus, elevated serum ERBB3 levels in otherwise healthy looking devils could predict possible DFT1 or CL in captive or wild devil populations and would have implications on the management, welfare and survival of Tasmanian devils. ERBB3 is also a therapeutic target and therefore the potential exists to consider modes of administration that may eradicate DFT1 from the wild. PMID:28591206

NHERF1, a novel GPER associated protein, increases stability and activation of GPER in ER-positive breast cancer.

PubMed

Meng, Ran; Qin, Qiong; Xiong, Ying; Wang, Yan; Zheng, Junfang; Zhao, Yuan; Tao, Tao; Wang, Qiqi; Liu, Hua; Wang, Songlin; Jiang, Wen G; He, Junqi

2016-08-23

G protein-coupled estrogen receptor (GPER) plays an important role in mediating the effects of estradiol. High levels of GPER have been implicated to associate with the malignant progress of invasive breast cancer (IBC). However, the mechanisms by which GPER protein levels were regulated remain unclear. In this study, PDZ protein Na+/H+ exchanger regulatory factor (NHERF1) was found to interact with GPER in breast cancer cells. This interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal PDZ binding motif of GPER. NHERF1 was demonstrated to facilitate GPER expression at post-transcriptional level and improve GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in a GPER/NHERF1 interaction-dependent manner. In addition, GPER protein levels are positively associated with NHERF1 protein levels in a panel of estrogen receptor (ER)-positive breast cancer cells. Furthermore, analysis of clinical IBC data from The Cancer Genome Atlas (TCGA) showed no significant difference in GPER mRNA levels between ER-positive IBC and normal breast tissues. However, gene set enrichment analysis (GSEA) showed that GPER signaling is ultra-activated in ER-positive IBC when compared with normal and its activation is positively associated with NHERF1 mRNA levels. Taken together, our findings identify NHERF1 as a new binding partner for GPER and its overexpression promotes protein stability and activation of GPER in ER-positive IBC. Our data indicate that regulation of GPER stability by NHERF1 may contribute to GPER-mediated carcinogenesis in ER-positive IBC.

[Use of epsilon aminocaproic acid in abnormal hemorrhage using intrauterine contraceptive devices].

PubMed

Rueda González, R

1969-01-01

Epsilon-aminocaproic acid was tested in 50 women suffering from excessive bleeding as a result of the use of IUDs. The drug was administered daily in 500 mg tablets, in doses of 1-2 g, during the first 5 days of menstruation. All cases were kept under observation for 10 months. Results were good in 38 cases (76 percent) (bleeding returned to normal levels), average in 7 cases (14 percent) (considerably reduced bleeding but still above normal), and without effe ct in 5 cases (10 percent), using a dose of 1 g daily. In these 5 cases, the dose was doubled during the next cycle: results were acceptable in 3 cases (60 percent), while in the other 2 bleeding persisted and the IUD had to be removed. 28 cases (56 percent) required treatment for only 1 cycle, the remaining 9 cycles observed being normal. Treatment during all 10 cycles was necessary in only 5 cases (10 percent). It is concluded that the drug is highly effective, and the small doses used rule out the risk of toxicity or thromboembolic com plications.

Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

PubMed Central

Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

2015-01-01

Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation.

PubMed

Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

2015-12-23

BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion.

Hepatoid adenocarcinoma of the lung without production of α-fetoprotein: A case report and review of the literature

PubMed Central

SUN, JI NING; ZHANG, BAO LONG; LI, LIN KUN; YU, HAI YAN; WANG, BIN

2016-01-01

Hepatoid adenocarcinoma of the lung (HAL) is a rare type of extrahepatic hepatoid adenocarcinoma. The majority of such cases that have been reported in the English literature have demonstrated elevated serum α-fetoprotein (AFP) and/or positive AFP expression on histopathological analysis, and have had poor prognoses. The current study reports an extremely rare case of HAL in the right upper lung without AFP production in a 59-year-old male patient. The patient underwent radical right upper lobectomy via video assisted thoracoscopic surgery. No signs of local recurrence or distant metastasis have been observed for 23 months after the surgery. The serum AFP level following surgery remained within the normal range. Although the diagnosis of HAL predominantly depends on pathological examination, a review of the literature demonstrates that HAL has certain characteristic features with regard to its clinical and computed tomography findings and prognoses, and clinicians should be aware that clinicians should be aware that monitoring serum AFP levels, as well as CT findings, remains important. PMID:27347123

Hepatoid adenocarcinoma of the lung without production of α-fetoprotein: A case report and review of the literature.

PubMed

Sun, Ji Ning; Zhang, Bao Long; Li, Lin Kun; Yu, Hai Yan; Wang, Bin

2016-07-01

Hepatoid adenocarcinoma of the lung (HAL) is a rare type of extrahepatic hepatoid adenocarcinoma. The majority of such cases that have been reported in the English literature have demonstrated elevated serum α-fetoprotein (AFP) and/or positive AFP expression on histopathological analysis, and have had poor prognoses. The current study reports an extremely rare case of HAL in the right upper lung without AFP production in a 59-year-old male patient. The patient underwent radical right upper lobectomy via video assisted thoracoscopic surgery. No signs of local recurrence or distant metastasis have been observed for 23 months after the surgery. The serum AFP level following surgery remained within the normal range. Although the diagnosis of HAL predominantly depends on pathological examination, a review of the literature demonstrates that HAL has certain characteristic features with regard to its clinical and computed tomography findings and prognoses, and clinicians should be aware that clinicians should be aware that monitoring serum AFP levels, as well as CT findings, remains important.

Iodinated Contrast Media Can Induce Long-Lasting Oxidative Stress in Hemodialysis Patients

PubMed Central

Hwang, Seun Deuk; Kim, Yoon Ji; Lee, Sang Heun; Cho, Deok Kyu; Cho, Yun Hyeong; Moon, Sung Jin; Lee, Sang Choel

2013-01-01

Purpose Due to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population. Materials and Methods We included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days. Results In the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure. Conclusion Our study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients. PMID:24142649

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio.

PubMed

Ross, Jaime M; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J; Olson, Lars

2010-11-16

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes.

2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children

PubMed Central

Lazarus, John; Brown, Rosalind S.; Daumerie, Chantal; Hubalewska-Dydejczyk, Alicja; Negro, Roberto; Vaidya, Bijay

2014-01-01

This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking. PMID:25114871

Saliva composition in three selected groups with normal stimulated salivary flow rates, but yet major differences in caries experience and dental erosion.

PubMed

Bardow, Allan; Lykkeaa, Joan; Qvist, Vibeke; Ekstrand, Kim; Twetman, Svante; Fiehn, Niels-Erik

2014-08-01

It was hypothesized that, by comparing matched subjects with major differences in these dental diseases, but yet normal saliva flow rates, it would be possible to obtain data on the effect of saliva composition on dental disease isolated from the effect of the flow rate. Thus, the aim of the study was to compare the major physicochemical characteristics of stimulated whole saliva in three groups of 85 subjects, each with normal saliva flow rates and at least 24 remaining teeth. A group with very little dental disease (healthy), a group with dental erosion (erosion) and a group with very high caries experience (caries) were chosen. Furthermore, the aim was to determine whether differences among groups could also be found on an individual level. Although it was not possible to retrieve three groups whose members were completely identical, the present study points in the direction that, on a group level, subjects with very little dental disease seemed to have a more favorable physicochemical saliva composition with respect to higher calcium, phosphate, bicarbonate, pH, degree of saturation with respect to hydroxyapatite and a lower critical pH (p < 0.05 or less). However, on an individual level the explanatory power for the saliva composition was only 10% for caries experience and only 11% for dental erosion (p < 0.001). The compositional analyses performed in this study on stimulated whole saliva, including major physicochemical characteristics of saliva, will most likely have little predictive value for future dental caries and erosion in single individuals.

Aberrant protein expression and frequent allelic loss of MSH3 in colorectal cancer with low-level microsatellite instability.

PubMed

Plaschke, Jens; Preußler, Mark; Ziegler, Andreas; Schackert, Hans K

2012-07-01

High level of microsatellite instability (MSI-H) in colorectal cancer (CRC) is caused by the inactivation of mismatch repair (MMR) genes; however, it is unknown for tumors with low level MSI (MSI-L). The protein complex involving MSH3 preferentially recognizes insertion/deletion loops (IDLs) of two to eight bases and di- and tetranucleotide repeats are affected in the majority of MSI-L CRC. We selected 10 and eight MSI-L CRCs from 228 and 204 patients with sporadic and hereditary disease, respectively. The tumors were analyzed for protein expression of MSH3, MSH2, MSH6, MLH1, and PMS2, and for mutations and loss of heterozygosity (LOH) in MSH3. Four tumors showed a markedly reduced MSH3 expression, whereas all 18 tumors had normal expression of the remaining MMR proteins. Twenty-five different sequence variants were identified. None of these results in a truncated protein, though L902W represents the first constitutional missense mutation in MSH3 predicted to be functional based on conservation among mutS homologues. All variants have also been found in normal DNA of the patients and in controls. LOH intragenic to MSH3 was evident for 12 of 16 (75%) informative tumors. Occurrence of sequence variants in normal DNA of the patients and in controls excludes somatic mutations and mutations specific to the CRC patient population, respectively. In contrast, the high frequency of LOH as well as the aberrant protein expression in some tumors indicates an involvement of MSH3 impairment in MSI-L CRC.

An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

PubMed

Savas-Erdeve, Senay; Yılmaz Agladioglu, Sebahat; Onder, Asan; Peltek Kendirci, Havva Nur; Bas, Veysel Nijat; Sagsak, Elif; Cetinkaya, Semra; Aycan, Zehra

2014-01-01

Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin. A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated. In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out. © 2014 S. Karger AG, Basel.

Pronounced reversible hyperammonemic encephalopathy associated with combined valproate-topiramate therapy in a 7-year-old girl.

PubMed

Weise, Sebastian; Syrbe, Steffen; Preuss, Matthias; Bertsche, Astrid; Merkenschlager, Andreas; Bernhard, Matthias K

2015-01-01

Valproate is one of the most frequently used anticonvulsive drugs in children and adults. Valproate is a generally well tolerated medication. However, encephalopathy with or without hyperammonemia is one of its rare adverse events. We present a 7-year-old girl who suffered from epilepsy with generalized tonic-clonic seizures and absence epilepsy. She was initially treated with topiramate. Methylprednisolone pulse therapy and long-term therapy with valproate were initiated due to an increase of seizure frequency. At day 5 of therapy, a further increase of seizure frequency was observed followed by lethargy and somnolence. Liver enzymes remained within normal range, but ammonia serum levels increased to a maximum of 544 mmol/l. Discontinuing valproate and starting potassium-benzoate and sodium-phenylbutyrate improved the clinical condition and ammonia serum levels. Haemodialysis was not required. Cranial magnetic resonance imaging ruled out brain edema. The patient was further on successfully treated with a combination of both, topiramate and levetiracetam. Seizures did not recur and development was normal until now (3 years later). To the best of our knowledge, we observed the highest ammonia serum levels ever reported in valproate-induced hyperammonemia with a complete remission of the subsequent encephalopathy. Topiramate might increase the risk of valproate-induced encephalopathy by carbonic anhydrase inhibition.

Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI.

PubMed

Wagner, Amy K; Brett, Christopher A; McCullough, Emily H; Niyonkuru, Christian; Loucks, Tammy L; Dixon, C Edward; Ricker, Joseph; Arenth, Patricia; Berga, Sarah L

2012-01-01

Acute hypogonadotropic hypogonadism (AHH) occurs frequently after TBI, as does chronic hypogonadotropic hypogonadism. However, AHH and persistent hypogonadotropic hypogonadism (PHH) after TBI are not well studied. The objective of this study was to characterize longitudinal hormone profiles and the impact of AHH and PHH on outcome. In this prospective cohort study, men with severe TBI (n = 38) had serum gonadal and gonadotropic hormones measured during weeks 1-52 post-injury. AHH, PHH and/or early resolving hypogonadotropic hypogonadism (ERHH) were based on temporal hormone assessments. PHH and hormone profiles were then compared to multiple outcome measures 6-12 months post-TBI. AHH affected 100% of the population, while 37% subsequently developed PHH. Acute testosterone (TEST) and estradiol/testosterone (E2/TEST) ratios were associated with PHH and outcome. Over time, post-acute TEST and E2 levels for the ERHH group approached normal range, while levels for the PHH group remained low. Post-acute gonadotrophin levels were within the normal range for both groups. PHH, along with lower post-acute TEST and E2 profiles, was associated with worse functional and cognitive outcomes at 6 and 12 months post-injury. These results support screening for post-acute secondary hypogonadism and further research to assess the mechanisms underlying PHH and associated functional and cognitive deficits.

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control.

PubMed

de Rooij, Laura P M H; Chan, Derek C H; Keyvani Chahi, Ava; Hope, Kristin J

2018-06-13

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved, however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSC, its implications for normal, perturbed and malignant hematopoiesis, as well as the most recent technological innovations aimed at RBP-RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

[Orbital decompression in Grave's ophtalmopathy].

PubMed

Longueville, E

2010-01-01

Graves disease orbitopathy is a complex progressive inflammatory disease. Medical treatment remains in all cases the proposed treatment of choice. Surgical treatment by bone decompression can be considered as an emergency mainly in cases of optic neuropathy or ocular hypertension not being controlled medically or in post-traumatic exophthalmos stage. Emergency bone decompression eliminates compression or stretching of the optic nerve allowing visual recovery. The uncontrolled ocular hypertension will benefit from decompression. The normalization of intraocular pressure may be obtained by this surgery or if needed by the use of postoperative antiglaucoma drops or even filtration surgery. In all operated cases, the IOP was normalized with an average decrease of 7.71 mmHg and a cessation of eye drops in 3/7 cases. Regarding sequelae, our therapeutic strategy involves consecutively surgery of the orbit, extraocular muscles and eyelids. The orbital expansion gives excellent results on the cosmetic level and facilitates the implementation of subsequent actions.

High accuracy diffuse horizontal irradiance measurements without a shadowband

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

Schlemmer, J.A; Michalsky, J.J.

1995-12-31

The standard method for measuring diffuse horizontal irradiance uses a fixed shadowband to block direct solar radiation. This method requires a correction for the excess skylight blocked by the band, and this correction varies with sky conditions. Alternately, diffuse horizontal irradiance may be calculated from total horizontal and direct normal irradiance. This method is in error because of angular (cosine) response of the total horizontal pyranometer to direct beam irradiance. This paper describes an improved calculation of diffuse horizontal irradiance from total horizontal and direct normal irradiance using a predetermination of the angular response of the total horizontal pyranometer. Wemore » compare these diffuse horizontal irradiance calculations with measurements made with a shading-disk pyranometer that shields direct irradiance using a tracking disk. Results indicate significant improvement in most cases. Remaining disagreement most likely arises from undetected tracking errors and instrument leveling.« less

High accuracy diffuse horizontal irradiance measurements without a shadowband

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

Schlemmer, J.A.; Michalsky, J.J.

1995-10-01

The standard method for measuring diffuse horizontal irradiance uses a fixed shadowband to block direct solar radiation. This method requires a correction for the excess skylight blocked by the band, and this correction varies with sky conditions. Alternately, diffuse horizontal irradiance may be calculated from the total horizontal and direct normal irradiance. This method is in error because of the angular (often referred to as cosine) response of the total horizontal pyranometer to direct beam irradiance. This paper describes an improved calculation of diffuse horizontal irradiance from total horizontal and direct normal irradiance using a predetermination of the angular responsemore » of the total horizontal pyranometer. The authors compare these diffuse horizontal irradiance calculations with measurements made with a shading-disk pyranometer that shields direct irradiance using a tracking disk. The results indicate significant improvement in most cases. The remaining disagreement most likely arises from undetected tracking errors and instrument leveling.« less

IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

PubMed

Zaydfudim, Victor M; Wang, Andrew Y; de Lange, Eduard E; Zhao, Zimin; Moskaluk, Christopher A; Bauer, Todd W; Adams, Reid B

2015-07-01

IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

Overview of Hypothyroidism in Pregnancy.

PubMed

Kroopnick, Jeffrey M; Kim, Caroline S

2016-11-01

Overt hypothyroidism in pregnancy, defined as an elevated serum thyroid-stimulating hormone (TSH) and reduced serum free thyroxine or a TSH >10 mIU/L, is known to have adverse effects on pregnancy. Subclinical hypothyroidism is typically defined as an elevated TSH and normal FT4 levels. There remains much controversy on the benefit of starting levothyroxine for mothers diagnosed with subclinical hypothyroidism. Recent studies are redefining the normal range for TSH in pregnancy, and the data on whether treatment of subclinical hypothyroidism improves outcomes for the mother and fetus are unclear. One confounding variable is the presence of thyroid peroxidase antibodies, as it may be a surrogate marker for other autoimmune disorders detrimental to pregnancy. If levothyroxine treatment is initiated, the dosing and monitoring strategy is different from nonpregnant individuals. Randomized clinical trials are underway that may better elucidate whether treatment of subclinical hypothyroidism is warranted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Systemic lupus erythematosus with organic brain syndrome: serial electroencephalograms accurately evaluate therapeutic efficacy.

PubMed

Kato, Takashi; Shiratori, Kyoji; Kobashigawa, Tsuyoshi; Hidaka, Yuji

2006-01-01

A 48-year-old man with systemic lupus erythematosus developed organic brain syndrome. High-dose prednisolone was ineffective, and somnolence without focal signs rapidly developed. Electroencephalogram (EEG) demonstrated a slow basic rhythm (3 Hz), but brain magnetic resonance imaging was normal. Somnolence resolved soon after performing plasma exchange (two sessions). However, memory dysfunction persisted, with EEG demonstrating mild abnormalities (7-8 Hz basic rhythm). Double-filtration plasmapheresis (three sessions) was done, followed by intravenous cyclophosphamide. Immediately after the first plasmapheresis session, memory dysfunction began to improve. After the second dose of cyclophosphamide, intellectual function resolved completely and EEG findings also normalized (basic rhythm of 10 Hz waves). Serial EEG findings precisely reflected the neurological condition and therapeutic efficacy in this patient. In contrast, protein levels in cerebrospinal fluid remained high and did not seem to appropriately reflect the neurological condition in this patient.

Speech Sound Processing Deficits and Training-Induced Neural Plasticity in Rats with Dyslexia Gene Knockdown

PubMed Central

Centanni, Tracy M.; Chen, Fuyi; Booker, Anne M.; Engineer, Crystal T.; Sloan, Andrew M.; Rennaker, Robert L.; LoTurco, Joseph J.; Kilgard, Michael P.

2014-01-01

In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA-) degrades cortical responses to speech sounds and increases trial-by-trial variability in onset latency. We tested the hypothesis that KIA- rats would be impaired at speech sound discrimination. KIA- rats needed twice as much training in quiet conditions to perform at control levels and remained impaired at several speech tasks. Focused training using truncated speech sounds was able to normalize speech discrimination in quiet and background noise conditions. Training also normalized trial-by-trial neural variability and temporal phase locking. Cortical activity from speech trained KIA- rats was sufficient to accurately discriminate between similar consonant sounds. These results provide the first direct evidence that assumed reduced expression of the dyslexia-associated gene KIAA0319 can cause phoneme processing impairments similar to those seen in dyslexia and that intensive behavioral therapy can eliminate these impairments. PMID:24871331

Use of computed tomography in diagnosing the cause of primary aldosteronism

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

White, E.A.; Schambelan, M.; Rost, C.R.

1980-12-25

Computed tomography (CT) was performed in 22 consecutive patients with primary aldosteronism to evaluate the usefulness of this technique in diagnosing and locating aldosterone-producing adenomas. Sixteen patients had severe hypokalemia, hyperaldosteronism, and elevated plasma levels of 18-hydroxycorticosterone suggestive of an adenoma. In 12 of these 16, a unilateral adrenal mass was demonstrated clearly, and in all 11 who had surgery an adenoma was confirmed. In the other four patients in this group, one adrenal gland was normal and the other was either not seen adequately or had minor abnormalities that could not be definitely classified; and adenoma was found inmore » the poorly visualized gland in each of the two patients who had surgery. The remaining six patients, who had milder biochemical abnormalities suggestive of idiopathic hyperaldosteronism, had bilateral adrenal enlargement or normal-appearing glands on scan and were not surgically explored.« less

Antacid aspiration in rabbits: a comparison of Mylanta and Bicitra.

PubMed

Eyler, S W; Cullen, B F; Murphy, M E; Welch, W D

1982-03-01

The effects of aspiration of (a) 2 ml of Mylanta (a particulate antacid) mixed with 2 ml of hydrochloric acid (pH 1.5), (b) 2 ml of half-strength Bicitra (a soluble antacid) mixed with 2 ml of hydrochloric acid (pH 1.5), (c) 4 ml of hydrochloric acid (pH 1.5), and (d) 4 ml of normal saline (pH 6.5) on arterial blood gas tensions and lung pathology were compared in anesthetized rabbits. PaO2 decreased similarly in all animals 15 minutes after aspiration, but recovered to normal levels 4 hours after aspiration of saline and 48 hours after aspiration of Bicitra. PaO2 remained depressed after aspiration of Mylanta and HCl. Gross and microscopic evidence of lung injury was most severe in animals that aspirated Mylanta. One animal died 8 hours after aspiration of Mylanta.

Food addiction and body-mass-index: a non-linear relationship.

PubMed

Meule, Adrian

2012-10-01

Excessive food consumption has been recognized to show similarities with substance dependence. Subsequently, it has been proposed that food addiction might contribute to the obesity epidemic. Recent studies using questionnaires for the assessment of food addiction have found statistically significant, but negligible positive correlations with body-mass-index (BMI). Moreover, group comparisons between food-addicted and non-addicted individuals in normal-weight or obese samples did not show differences in BMI. However, the prevalence of food addiction diagnoses is remarkably increased in obese individuals. In the current article, it is suggested that there might be a cubic relationship between food addiction and BMI. Food addiction symptomatology may remain stable in the under- and normal-weight range, increase in the overweight- and obese range, and level off at severe obesity. Empirical data in support of this view are presented. Copyright © 2012 Elsevier Ltd. All rights reserved.

Snipper, an Eri1 homologue, affects histone mRNA abundance and is crucial for normal Drosophila melanogaster development.

PubMed

Alexiadis, Anastasios; Delidakis, Christos; Kalantidis, Kriton

2017-07-01

The conserved 3'-5' RNA exonuclease ERI1 is implicated in RNA interference inhibition, 5.8S rRNA maturation and histone mRNA maturation and turnover. The single ERI1 homologue in Drosophila melanogaster Snipper (Snp) is a 3'-5' exonuclease, but its in vivo function remains elusive. Here, we report Snp requirement for normal Drosophila development, since its perturbation leads to larval arrest and tissue-specific downregulation results in abnormal tissue development. Additionally, Snp directly interacts with histone mRNA, and its depletion results in drastic reduction in histone transcript levels. We propose that Snp protects the 3'-ends of histone mRNAs and upon its absence, histone transcripts are readily degraded. This in turn may lead to cell cycle delay or arrest, causing growth arrest and developmental perturbations. © 2017 Federation of European Biochemical Societies.

Changes in Fasting Plasma Glucose Levels with Ribavirin and Pegylated Interferon Treatment in Normal and Impaired Glucose Tolerant Patients with Chronic Hepatitis C

PubMed Central

Sarasombath, Ongkarn; Suwantarat, Nuntra; Tice, Alan D

2012-01-01

Background Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). Methods A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. Results The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. Conclusions In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding. PMID:22737650

Hyperghrelinemia in Prader-Willi Syndrome Begins in Early Infancy Long Before the Onset of Hyperphagia

PubMed Central

Kweh, Frederick A.; Miller, Jennifer L.; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J.; Goldstone, Anthony P.; Driscoll, Daniel J.

2015-01-01

Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P<0.001) higher in earlier nutritional phases: phase 1a (7,906 ± 5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P=0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. PMID:25355237

Hyperghrelinemia in Prader-Willi syndrome begins in early infancy long before the onset of hyperphagia.

PubMed

Kweh, Frederick A; Miller, Jennifer L; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J; Goldstone, Anthony P; Driscoll, Daniel J

2015-01-01

Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P < 0.001) higher in earlier nutritional phases: phase 1a (7,906  ±  5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P = 0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. © 2014 Wiley Periodicals, Inc.

Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome.

PubMed

Mahdi, Abbas Ali; Fatima, Ghizal; Das, Siddhartha Kumar; Verma, Nar Singh

2011-04-01

Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body's circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels.

A low glycemic index staple diet reduces postprandial glucose values in Asian women with gestational diabetes mellitus.

PubMed

Hu, Zhi-Geng; Tan, Rong-Shao; Jin, Di; Li, Wei; Zhou, Xiao-Yan

2014-12-01

A low glycemic index (GI) diet is beneficial for glucose control in patients with diabetes mellitus. This study aimed to investigate the influence of a low-GI diet on postprandial glucose levels in women with gestational diabetes mellitus (GDM). Pregnant women with GDM were randomized to receive a normal diabetic control diet or a low-GI staple diet for 5 days. A low-GI staple food was used to replace rice in lunch and dinner for the low-GI staple diet group, whereas the total energy and carbohydrate levels remained equal in both groups. Fasting and postprandial glucose levels were determined daily. A total of 140 pregnant women with GDM were included in the study, including 66 in the low-GI staple diet group and 74 in the normal diabetic diet control group. No differences existed in baseline characteristics between the 2 groups (all P > 0.05). After dietary intervention, glucose levels were significantly reduced in the low-GI staple diet group (all P < 0.01) and the control group (all P < 0.008). Postintervention glucose values after breakfast, lunch, and dinner were significantly reduced in the treatment group compared with those in the control group (all P < 0.05). The percentage changes from baseline of all glucose values were significantly greater in the treatment group than in the control group (all P < 0.05). A low-GI staple diet significantly reduces postprandial glucose levels in women with GDM.

Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein

PubMed Central

Laeger, Thomas; Reed, Scott D.; Henagan, Tara M.; Fernandez, Denise H.; Taghavi, Marzieh; Addington, Adele; Münzberg, Heike; Martin, Roy J.; Hutson, Susan M.

2014-01-01

Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P < 0.05). Circulating BCAA levels were reduced the day after LP diet exposure, but levels subsequently increased and normalized by day 4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis on day 2 of diet exposure were reduced in LP rats, but this effect was most prominent postprandially. Despite these diet-induced changes in BCAA levels, reducing dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet. PMID:24898843

Instrumented roll technology for the design space development of roller compaction process.

PubMed

Nesarikar, Vishwas V; Vatsaraj, Nipa; Patel, Chandrakant; Early, William; Pandey, Preetanshu; Sprockel, Omar; Gao, Zhihui; Jerzewski, Robert; Miller, Ronald; Levin, Michael

2012-04-15

Instrumented roll technology on Alexanderwerk WP120 roller compactor was developed and utilized successfully for the measurement of normal stress on ribbon during the process. The effects of process parameters such as roll speed (4-12 rpm), feed screw speed (19-53 rpm), and hydraulic roll pressure (40-70 bar) on normal stress and ribbon density were studied using placebo and active pre-blends. The placebo blend consisted of 1:1 ratio of microcrystalline cellulose PH102 and anhydrous lactose with sodium croscarmellose, colloidal silicon dioxide, and magnesium stearate. The active pre-blends were prepared using various combinations of one active ingredient (3-17%, w/w) and lubricant (0.1-0.9%, w/w) levels with remaining excipients same as placebo. Three force transducers (load cells) were installed linearly along the width of the roll, equidistant from each other with one transducer located in the center. Normal stress values recorded by side sensors and were lower than normal stress values recorded by middle sensor and showed greater variability than middle sensor. Normal stress was found to be directly proportional to hydraulic pressure and inversely to screw to roll speed ratio. For active pre-blends, normal stress was also a function of compressibility. For placebo pre-blends, ribbon density increased as normal stress increased. For active pre-blends, in addition to normal stress, ribbon density was also a function of gap. Models developed using placebo were found to predict ribbon densities of active blends with good accuracy and the prediction error decreased as the drug concentration of active blend decreased. Effective angle of internal friction and compressibility properties of active pre blend may be used as key indicators for predicting ribbon densities of active blend using placebo ribbon density model. Feasibility of on-line prediction of ribbon density during roller compaction was demonstrated using porosity-pressure data of pre-blend and normal stress measurements. Effect of vacuum to de-aerate pre blend prior to entering the nip zone was studied. Varying levels of vacuum for de-aeration of placebo pre blend did not affect the normal stress values. However, turning off vacuum completely caused an increase in normal stress with subsequent decrease in gap. Use of instrumented roll demonstrated potential to reduce the number of DOE runs by enhancing fundamental understanding of relationship between normal stress on ribbon and process parameters. Copyright © 2012 Elsevier B.V. All rights reserved.

Ground-water levels in alluvium on the South coast of Puerto Rico, February 1978

USGS Publications Warehouse

Diaz, Jose R.

1979-01-01

Ground-water levels in the alluvial aquifer of the south coast of Puerto Rico in February 1978 were similar to or slightly higher than those of February 1977. Water levels rose about 2 to 3 meters in the northern section near the foothills in the coastal plain area from Salinas to Patillas and in the Guanica-Penuelas area. Pumpage remained unchanged in most of the areas under study. Pumping-water levels were above mean sea level in all industrial well fields. Pumping and static water levels were below mean sea level (1 to 3 meters), in public supply and irrigation wells in the areas of Playa de Ponce, Descalabrado-Punta Petrona, and in the vicinity of the town of Salinas. These levels are considered to be normal for the dry season in these highly irrigated areas. Sixty-four water samples collected from irrigation, industrial and salinity observation wells exhibited similar or lower chloride concentration than in previous years. The average chloride concentration for 1978 was 57 milligrams per liter. (USGS)

Size distribution and sorption of polychlorinated biphenyls during haze episodes

NASA Astrophysics Data System (ADS)

Zhu, Qingqing; Liu, Guorui; Zheng, Minghui; Zhang, Xian; Gao, Lirong; Su, Guijin; Liang, Yong

2018-01-01

There is a lack of studies on the size distribution of polychlorinated biphenyls (PCBs) during haze days, and their sorption mechanisms on aerosol particles remain unclear. In this study, PCBs in particle-sized aerosols from urban atmospheres of Beijing, China were investigated during haze and normal days. The concentrations, gas/particle partitioning, size distribution, and associated human daily intake of PCBs via inhalation were compared during haze days and normal days. Compared with normal days, higher particle mass-associated PCB levels were measured during haze days. The concentrations of ∑PCBs in particulate fractions were 11.9-134 pg/m3 and 6.37-14.9 pg/m3 during haze days and normal days, respectively. PCBs increased with decreasing particle size (>10 μm, 10-2.5 μm, 2.5-1.0 μm, and ≤1.0 μm). During haze days, PCBs were overwhelmingly associated with a fine particle fraction of ≤1.0 μm (64.6%), while during normal days the contribution was 33.7%. Tetra-CBs were the largest contributors (51.8%-66.7%) both in the gas and particle fractions during normal days. The profiles in the gas fraction were conspicuously different than those in the PM fractions during haze days, with di-CBs predominating in the gas fraction and higher homologues (tetra-CBs, penta-CBs, and hexa-CBs) concurrently accounting for most of the PM fractions. The mean-normalized size distributions of particulate mass and PCBs exhibited unimodal patterns, and a similar trend was observed for PCBs during both days. They all tended to be in the PM fraction of 1.0-2.5 μm. Adsorption might be the predominating mechanism for the gas-particle partitioning of PCBs during haze days, whereas absorption might be dominative during normal days.

Analysis of the original causes of placental oxidative stress in normal pregnancy and pre-eclampsia: a hypothesis.

PubMed

Yang, Xiang; Guo, Lili; Li, Huaifang; Chen, Xinliang; Tong, Xiaowen

2012-07-01

Pre-eclampsia (PE) and eclampsia remain enigmatic despite intensive research. Growing evidence suggests that placental oxidative stress (OS) is involved in the etiopathogenesis of pre-eclampsia. Reduced perfusion as a result of abnormal placentation was proposed to be responsible for placental OS in PE. However, placental OS was also observed in normal pregnancy. The exact differences and correlation of placental OS in PE and normal pregnancy remain elusive. In this review, we attempted to link both normal pregnancy and PE on the causes of placental OS and proposed a hypothesis that placental OS in normal pregnancy, plus the exploration of other placental and/or maternal factors, could provide a novel explanation of that in PE. We concluded that pregnancy, placental abnormality and preexisting maternal constitutional conditions are three principle factors that could contribute to placental OS in PE. The specific causes in each clinical case could be heterogeneous, which requires individual analysis.

Influence of time, temperature and coagulation on the measurement of C3, C3 split products and C4.

PubMed

Sinosich, M J; Teisner, B; Brandslund, I; Fisher, M; Grudzinskas, J G

1982-11-26

Quantitative and qualitative immunoelectrophoretic analyses of circulating C3, C3 split products and C4 were performed in matched EDTA plasma and serum obtained from 5 normal subjects and stored for up to 48 h at room temperature (18 degrees C-22 degrees C) and 4 degrees C. Fluctuations in apparent levels of C3 were greater in serum than plasma stored at room temperature, a fall in levels seen by 24 h being followed by a significant increase. By contrast, levels of C3 did not alter if stored at 4 degrees C. C4 levels in both EDTA plasma and serum remained unchanged for 24 h, a slight decrease being seen at 48 h. Levels of C4 remained constant if samples were stored at 4 degrees C. Crossed immunoelectrophoresis revealed a significant progressive decrease in C3 levels and a simultaneous increase in C3c occurring after 4 h in serum and 8 h in EDTA plasma, stored at room temperature. In studies conducted at 4 degrees C, similar but delayed fluctuations were seen. A progressive and significant increase in C3d levels was seen in both plasma and serum samples stored at room temperature, levels rising to 276% (plasma) and 308% (serum) of levels seen at zero time. At 4 degrees C marginal increases in C3d levels only were observed. These results suggest that in vitro degradation of C3 and C4 are readily facilitated by temperature, time and coagulation, and that conditions of collection and storage of samples must be optimized for the accurate definition of activation of the complement cascade.

The cell biology of aging.

PubMed

Hayflick, L

1985-02-01

It is only within the past ten years that biogerontology has become attractive to a sufficient number of biologists so that the field can be regarded as a seriously studied discipline. Cytogerontology, or the study of aging at the cellular level, had its genesis about 20 years ago when the dogma that maintained that cultured normal cells could replicate forever was overturned. Normal human and animal cells have a finite capacity to replicate and function whether they are cultured in vitro or transplanted as grafts in vivo. This phenomenon has been interpreted to be aging at the cellular level. Only abnormal somatic cells are capable of immortality. In recent years it has been found that the number of population doublings of which cultured normal cells are capable is inversely proportional to donor age. There is also good evidence that the number of population doublings of cultured normal fibroblasts is directly proportional to the maximum lifespan of ten species that have been studied. Cultures prepared from patients with accelerated aging syndromes (progeria and Werner's syndrome) undergo far fewer doublings than do those of age-matched controls. The normal human fibroblast cell strain WI-38 was established in 1962 from fetal lung, and several hundred ampules of these cells were frozen in liquid nitrogen at that time. These ampules have been reconstituted periodically and shown to be capable of replication. This represents the longest period of time that a normal human cell has ever been frozen. Normal human fetal cell strains such as WI-38 have the capacity to double only about 50 times. If cultures are frozen at various population doublings, the number of doublings remaining after reconstitution is equal to 50 minus the number of doublings that occurred prior to freezing. The memory of the cells has been found to be accurate after 23 years of preservation in liquid nitrogen. Normal human cells incur many physiologic decrements that herald the approach of their failure to divide. Many of these functional decrements are identical to decrements found in humans as they age. Thus it is likely that these decrements are also the precursors of age changes in vivo. The finite replicative capacity of normal cells is never seen to occur in vivo because aging and death of the individual occurs well before the doubling limit is reached.

Chromosome Aberrations in Normal and Ataxia-Telangiectasia Cells Exposed to Heavy Ions

NASA Technical Reports Server (NTRS)

Kawata, T.; Ito, H.; Liu, C.; Shigematsu, N.; George, K.; Cucinotta, F. A.

2007-01-01

Although cells derived from Ataxia Telangiectasia (AT) patients are known to exhibit abnormal responses to ionizing radiations, its underlying mechanism still remains unclear. Previously, the authors reported that at the same gamma-irradiation dose AT cells show higher frequencies of misrepair and deletions compared to normal human fibroblast cells. In this study, we investigated the effects of heavy ions beams on chromosomal aberrations in normal and AT cells. Normal and AT fibroblast cells arrested at G0/G1 phase were irradiated with 2 Gy of X-rays, 490 MeV/u Silicon (LET 55 keV/m), 500 MeV/u Iron (LET 185 keV/m) and 200 MeV/u Iron (LET 440 keV/m) particles, and then cells were allowed to repair for 24 hours at 37 degrees before subculture. Calyculin-A induced PCC method was employed to collect G2/M chromosomes and whole DNA probes 1 and 3 were used to analyze chromosomal aberrations such as color-junctions, deletions, simple exchanges (incomplete and reciprocal exanges) and complex-type exchanges. The percentages of aberrant cells were higher when normal and AT cells were exposed to heavy ions compared to X-rays, and had a tendency to increase with increasing LET up to 185 keV/m and then decreased at 440 keV/m. When the frequency of color-junctions per cell was compared after X-ray exposure, AT cells had around three times higher frequency of color-junctions (mis-rejoining) than normal cells. However, at 185 keV/m there was no difference in the frequency of color-junctions between two cell lines. It was also found that the frequency of simple exchanges per cell was almost constant in AT cells regardless LET levels, but it was LET dependent for normal cells. Interestingly, the frequency of simple exchanges was higher for AT cells when it was compared at 185 keV/m but AT cells had more complex-type exchanges at the same LET levels. Heavy ions are more efficient in inducing chromosome aberrations in normal and AT cells compared to X-rays, and the aberration types between normal and AT fibroblast appeared different probably due to difference in the ATM gene function.

[Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers].

PubMed

Hu, Xiao-ye; Zou, Qing-feng; Jin, Chuan; Li, Wei-dong; Chen, Wen-sheng; Ma, Lei

2010-06-01

To evaluate the clinical efficacy of zoledronic acid combined with chemotherapy in the management of skeletal metastasis of non-small cell lung cancer (NSCLC) and investigate the value in urine amino-terminal telopeptide of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBALP) in monitoring skeletal metastasis of NSCLC. From February, 2007 to January, 2009, 32 NSCLC patients with bone metastases received treatment with zoledronic acid at the dose of 4 mg given every 3 weeks and platinum-based chemotherapy (each cycle lasting for 3 weeks). Before and during the treatments, uNTX and sBALP were measured in these patients using ELISA and precipitation with wheat germ lectin, respectively. The patients were followed up for skeletal-related events (SREs) and status of survival. A significant decrease occurred in the pain scores and analgesic use in the patients after the therapy. SREs were not observed during the treatment. Serum creatinine and calcium levels underwent no significant variation during the treatment. Eleven patients reported 14 possible zoledronic acid-related adverse events. The concentration of uNTX and sBALP in patients with bone metastases was above the upper limit of the normal range. A positive correlation was observed between the levels of the markers and the extent of bone metastases. At the third month, uNTX and sBALP were significantly lowered, but radionuclide whole-body bone imaging showed no obvious changes. Of the 32 patients, 24 had elevated uNTX values, which became normal after the treatment in 15 patients and remained elevated in the other 9 patients. SREs occurred in these two subgroups at the rates of 53% and 89% (P=0.039), respectively. Twenty-six patients had elevated sBALP level, and 16 of them exhibited normal sBALP level after the treatment. The incidences of SREs in the patients with elevated and normal sBALP level were 50% and 90% (P=0.038), respectively. The levels of uNTX/Cr and sBALP were not correlated to the survival of the patients. Zoledronic acid combined with chemotherapy is an effective treatment for NSCLC with bone metastases. Zoledronic acid is safe and well tolerated. Urinary NTX and serum BALP have a high value in the diagnosis, therapeutic effect monitoring and SRE prediction of NSCLC with bone metastases.

Impaired detection of happy facial expressions in autism.

PubMed

Sato, Wataru; Sawada, Reiko; Uono, Shota; Yoshimura, Sayaka; Kochiyama, Takanori; Kubota, Yasutaka; Sakihama, Morimitsu; Toichi, Motomi

2017-10-17

The detection of emotional facial expressions plays an indispensable role in social interaction. Psychological studies have shown that typically developing (TD) individuals more rapidly detect emotional expressions than neutral expressions. However, it remains unclear whether individuals with autistic phenotypes, such as autism spectrum disorder (ASD) and high levels of autistic traits (ATs), are impaired in this ability. We examined this by comparing TD and ASD individuals in Experiment 1 and individuals with low and high ATs in Experiment 2 using the visual search paradigm. Participants detected normal facial expressions of anger and happiness and their anti-expressions within crowds of neutral expressions. In Experiment 1, reaction times were shorter for normal angry expressions than for anti-expressions in both TD and ASD groups. This was also the case for normal happy expressions vs. anti-expressions in the TD group but not in the ASD group. Similarly, in Experiment 2, the detection of normal vs. anti-expressions was faster for angry expressions in both groups and for happy expressions in the low, but not high, ATs group. These results suggest that the detection of happy facial expressions is impaired in individuals with ASD and high ATs, which may contribute to their difficulty in creating and maintaining affiliative social relationships.

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers

PubMed Central

Anderlini, Paolo

2015-01-01

Purpose of Review Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed. Recent Findings In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. G-CSF receptors were identified in a variety of non-myeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for PBPCs, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare. Summary rhG-CSF effects in healthy volunteers, while normally transient and self-limiting, are now believed to be more complex and heterogeneous that previously thought. While rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals. PMID:19057203

Immunomodulatory actions of central ghrelin in diet-induced energy imbalance.

PubMed

Stevanovic, Darko; Starcevic, Vesna; Vilimanovich, Urosh; Nesic, Dejan; Vucicevic, Ljubica; Misirkic, Maja; Janjetovic, Kristina; Savic, Emina; Popadic, Dusan; Sudar, Emina; Micic, Dragan; Sumarac-Dumanovic, Mirjana; Trajkovic, Vladimir

2012-01-01

We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1β, IFN-γ) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1β, IL-6, IFN-γ, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-β remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 μg/day) for five consecutive days significantly reduced TNF, IL-1β and IFN-γ levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of IFN-γ, IL-17, IL-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. Copyright © 2011 Elsevier Inc. All rights reserved.

Late effect of subtotal thyroidectomy and radioactive iodine therapy on calcitonin secretion and bone mineral density in women treated for Graves' disease

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

Lowery, W.D.; Thomas, C.G. Jr.; Awbrey, B.J.

1986-12-01

This study was designed to evaluate the effect of subtotal thyroidectomy and/or radioactive iodine therapy on plasma immunocalcitonin (iCT) levels and bone densities in patients treated for Graves' disease. Forty-eight women whose ages ranged from 29 to 79 years (mean, 55 years) were evaluated. All were at least 10 years beyond treatment. Fourteen patients had undergone subtotal thyroidectomy, 22 had received radioactive iodine therapy, and 12 had received both. Serum calcitonin levels were measured with the patient fasting and at 30 minutes and 2 hours after the ingestion of 15 mg of calcium in orange juice. Single photon absorptiometry wasmore » used to measure bone mineral density of the middle and distal radius. The mean fasting plasma levels of iCT for patients undergoing subtotal thyroidectomy was 27 +/- 2 mumol/L; women treated with radioactive iodine, 26 +/- 2; women undergoing subtotal thyroidectomy followed by radioactive iodine, 24 +/- 2, and for normal control women, 48.5 +/- 4.7. The mean stimulated iCT level of each of the patient groups was significantly lower than that of the normal controls (p = 0.01). There were no significant differences among the groups. Although there was an increased loss of bone mineral density in postmenopausal patients, with age and race as covariates, the bone densities of the distal radius in women undergoing subtotal thyroidectomy and/or receiving radioactive iodine were not significantly lower than those of normal control subjects (p greater than 0.05). These findings are consistent with other observations that patients treated by thyroidectomy and/or radioactive iodine for Graves' disease have lower basal levels of calcitonin and decreased calcitonin response to a provocative stimulus. Whether this loss of calcitonin reserve is a significant factor in development of postmenopausal osteoporosis remains unanswered.« less

SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in esophageal cancer cells

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

Shinozuka, Eriko; Miyashita, Masao; Mizuguchi, Yoshiaki, E-mail: yoshi1224@gmail.com

2013-01-04

Highlights: Black-Right-Pointing-Pointer SnoN modulated miR-720, miR-1274A, and miR-1274B expression levels in TE-1 cells. Black-Right-Pointing-Pointer miR-720 and miR-1274A suppressed the expression of target proteins p63 and ADAM9. Black-Right-Pointing-Pointer Silencing of SnoN significantly upregulated cell proliferation in TE-1 cells. Black-Right-Pointing-Pointer Esophageal cancer tissues have lower SnoN expression levels than normal tissues. Black-Right-Pointing-Pointer Esophageal cancer tissues have higher miR-720 expression levels than normal tissues. -- Abstract: It is now evident that changes in microRNA are involved in cancer progression, but the mechanisms of transcriptional regulation of miRNAs remain unknown. Ski-related novel gene (SnoN/SKIL), a transcription co-factor, acts as a potential key regulator withinmore » a complex network of p53 transcriptional repressors. SnoN has pro- and anti-oncogenic functions in the regulation of cell proliferation, senescence, apoptosis, and differentiation. We characterized the roles of SnoN in miRNA transcriptional regulation and its effects on cell proliferation using esophageal squamous cell carcinoma (ESCC) cells. Silencing of SnoN altered a set of miRNA expression profiles in TE-1cells, and the expression levels of miR-720, miR-1274A, and miR-1274B were modulated by SnoN. The expression of these miRNAs resulted in changes to the target protein p63 and a disintegrin and metalloproteinase domain 9 (ADAM9). Furthermore, silencing of SnoN significantly upregulated cell proliferation in TE-1 cells, indicating a potential anti-oncogenic function. These results support our observation that cancer tissues have lower expression levels of SnoN, miR-720, and miR-1274A compared to adjacent normal tissues from ESCC patients. These data demonstrate a novel mechanism of miRNA regulation, leading to changes in cell proliferation.« less

Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

PubMed

Russell, Steven J; El-Khatib, Firas H; Nathan, David M; Damiano, Edward R

2010-11-01

During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BG<70 mg/dl). After a global adjustment of control algorithm parameters used to model insulin absorption and clearance to more closely match insulin pharmacokinetic (PK) parameters observed in the study cohort, administration of glucagon by the control system was more effective in preventing hypoglycemia. We evaluated the role of plasma insulin and plasma glucagon levels in determining whether glucagon was effective in preventing hypoglycemia. We identified and analyzed 36 episodes during which glucagon was given and categorized them as either successful or unsuccessful in preventing hypoglycemia. In 20 of the 36 episodes, glucagon administration prevented hypoglycemia. In the remaining 16, BG fell below 70 mg/dl (12 of the 16 occurred during experiments performed before PK parameters were adjusted). The (dimensionless) levels of plasma insulin (normalized relative to each subject's baseline insulin level) were significantly higher during episodes ending in hypoglycemia (5.2 versus 3.7 times the baseline insulin level, p=.01). The relative error in the control algorithm's online estimate of the instantaneous plasma insulin level was also higher during episodes ending in hypoglycemia (50 versus 30%, p=.003), as were the peak plasma glucagon levels (183 versus 116 pg/ml, p=.007, normal range 50-150 pg/ml) and mean plasma glucagon levels (142 versus 75 pg/ml, p=.02). Relative to mean plasma insulin levels, mean plasma glucagon levels tended to be 59% higher during episodes ending in hypoglycemia, although this result was not found to be statistically significant (p=.14). The rate of BG descent was also significantly greater during episodes ending in hypoglycemia (1.5 versus 1.0 mg/dl/min, p=.02). Microdose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today. © 2010 Diabetes Technology Society.

Nutritional status and dietary intake among pregnant women in relation to pre-pregnancy body mass index in Japan.

PubMed

Uno, Kaoru; Takemi, Yukari; Hayashi, Fumi; Hosokawa, Momo

2016-01-01

Objective The present study examined nutritional status and dietary intake of pregnant women in Japan in relation to pre-pregnancy body mass index (BMI).Methods Participants included 141 Japanese women with singleton pregnancies, from the outpatient department of the S hospital, Gunma prefecture, Japan. Two-day food records, dietary assessment questionnaires, and clinical records were obtained at 20 weeks gestation. Nine patients were excluded from the study due to morning sickness. The remaining 132 participants were divided into 3 groups according to pre-pregnancy BMI: underweight, normal weight, and overweight. Nutritional status and dietary intake were analyzed in relation to BMI using the chi-square test, Fisher's exact test, Kruskal-Wallis test, one-way analysis of variance, and analysis of covariance with adjustment for age, employment status, and total energy intake.Results Women who were underweight before pregnancy were more frequently working full-time than normal weight and overweight women. Underweight women were also more frequently anemic (P=0.038, underweight 39.3%, normal weight 24.7%, overweight 0%) and had lower mean hemoglobin (Hb) (P=0.021, underweight 11.3 g/dL, normal weight 11.6 g/dL, overweight 12.1 g/dL) and hematocrit (Hct) levels (P=0.025, underweight 33.7%, normal weight 34.3%, overweight 36.0%). Their dietary intake of protein, iron, magnesium, and folic acid was lower than that of normal weight and overweight women. Their meals tended to include fewer meat, fish, egg, and soybean dishes (underweight, mean of 4.7 servings per day; normal weight, 6.1 servings; overweight, 6.1 servings).Conclusion Pregnant women who were underweight before pregnancy had increased risk of anemia as well as reduced Hb and Hct levels. They had lower dietary intake of protein, iron and folic acid compared to women in the other BMI categories. Anemia and these nutrient deficiencies are known risk factors for low birth weight. Our findings suggest the importance of providing underweight pregnant women with support to improve dietary intake during their pregnancy, especially to increase intake of protein and iron through consumption of fish and meat dishes.

TOPEX/El Niño Watch - La Niña Barely Has a Pulse, June 18, 1999

NASA Image and Video Library

1999-08-23

Lingering just a month ago in the eastern Pacific Ocean, the La Niña phenomenon, with its large volume of chilly water, barely has a pulse this month, according to new satellite data from NASA U.S.-French TOPEX/Poseidon mission. The data, taken during a 10-day cycle of data collection ending June 18, show that the equatorial Pacific Ocean is warming up and returning to normal (green) as La Niña all but vanishes. The warming trend is most apparent in the equatorial Pacific Ocean, where only a few patches of cooler, low sea levels (seen in blue and purple) remain. The blue areas are between 5 and 13 centimeters (2 and 5 inches) below normal, whereas the purple areas range from 14 to 18 centimeters (6 to 7 inches) below normal. Like its counterpart, El Niño, a La Niña condition will influence global climate and weather until it has completely subsided. As summer begins in the northern hemisphere, lower-than-normal sea surface levels and cool ocean temperatures persist in the northeastern Gulf of Alaska and along the western coast of North America. In contrast, the trend is the opposite over most of the Pacific, where above-normal sea surface heights and warmer ocean temperatures (indicated by the red and white areas) appear to be increasing and dominating the overall Pacific Ocean. Red areas are about 10 centimeters (4 inches) above normal; white areas show the sea surface height is between 14 and 32 centimeters (6 and 13 inches) above normal. Scientists are not ready to administer last rites to La Niña, though. In the last 12 months, the pool of unusually cold water in the Pacific has shrunk (warmed) several times before cooling (expanding) again. This summer's altimeter data will help them determine whether La Niña has truly dissipated or whether they will see another resurgence of cool water in the Pacific. http://photojournal.jpl.nasa.gov/catalog/PIA01586

[Phospholipids under combined ozone-oxygen administration].

PubMed

Müller-Tyl, E; Hernuss, P; Salzer, H; Reisinger, L; Washüttl, J; Wurst, F

1975-01-01

The parenterally application of oxygen-ozone gas mixture gives good resultats in the treatment of various deseases. Ozone seems to influence the metabolic process of fat, so it was of interest to analyse this influence especially to phospholipids. 40 women with gynaecological cancer got 10 ml oxygen-ozone gas mixture with a content of 450 gamma ozone into the cubital vene. Venous blood was removed before and 10 minutes after application and the level of lecithin, lysolecithin, cephalin and spingomyelin was determined by the method of Randerath. A decrease of all four substances was obvious, although all values remained in normal range.

XRF investigation on skeletal remains from King Peter III of Aragon (1239-1285 A.D.) and Queen Blanche of Anjou (1280-1310 A.D.)

NASA Astrophysics Data System (ADS)

Piga, Giampaolo; Brunetti, Antonio; Lasio, Barbara; Enzo, Stefano; Malgosa, Assumpció

2014-03-01

We conducted an X-Ray Fluorescence investigation on bone fragments belonging to King Peter III of Aragon and Queen Blanche of Anjou. The spectroscopic analysis was carried out in selected points of the bone fragments. Several transitional elements normally unexpected in the bone composition have been found at varying level of concentration. The presence of these elements was interpreted in relation to chemical treatments for mummification of bodies as well as to dietary habits, including tools used for cooking and for the consumption of food.

Association between cardiorespiratory fitness and body fat in girls

PubMed Central

Minatto, Giseli; de Sousa, Thiago Ferreira; de Carvalho, Wellington Roberto Gomes; Ribeiro, Roberto Régis; Santos, Keila Donassolo; Petroski, Edio Luiz

2016-01-01

Abstract Objective: To estimate the prevalence of low cardiorespiratory fitness and its association with excess body fat, considering the sexual maturation and economic level in female adolescents. Methods: Cross-sectional, epidemiological study of 1223 adolescents (10-17 years) from the public school system of Cascavel, PR, Brazil, in 2006. We analyzed the self-assessed sexual maturation level (prepubertal, pubertal and post-pubertal), the economic level (high and low) through a questionnaire and body fat (normal and high) through triceps and subscapular skinfolds. The 20-meter back-and-forth test was applied to estimate maximum oxygen consumption. Cardiorespiratory fitness was assessed according to reference criteria and considered low when the minimum health criterion for age and sex was not met. Chi-square test and logistic regression were applied, with a significance level of 5%. Results: The prevalence of low cardiorespiratory fitness was 51.3%, being associated with all study variables (p<0.001). At the crude analysis, adolescents with high body fat were associated with low cardiorespiratory fitness, when compared to those with normal body fat (OR=2.76; 95%CI: 2.17-3.52). After adjustment by sexual maturation, this association remained valid and showed an effect that was 1.8-fold higher (95%CI: 1.39-2.46) and after adjusting by economic level, the effect was 1.9-fold higher (95%CI: 1.45-2.61). Conclusions: Approximately half of the assessed girls showed unsatisfactory levels of cardiorespiratory fitness for health, which was associated with high body fat, regardless of sexual maturation level and economic level. Effective public health measures are needed, with particular attention to high-risk groups. PMID:27131896

Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period.

PubMed

Nagasaka, Hironori; Okano, Yoshiyuki; Tsukahara, Hirokazu; Shigematsu, Yosuke; Momoi, Toru; Yorifuji, Junko; Miida, Takashi; Ohura, Toshihiro; Kobayashi, Keiko; Saheki, Takeyori; Hirano, Kenichi; Takayanagi, Masaki; Yorifuji, Tohru

2009-05-01

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) shows diverse metabolic abnormalities such as urea cycle dysfunction together with citrullinemia, galactosemia, and suppressed gluconeogenesis. Such abnormalities apparently resolve during the first year of life. However, metabolic profiles of the silent period remain unknown. We analyzed oxidative stress markers and profiles of amino acids, carbohydrates, and lipids in 20 asymptomatic children with aspartate/glutamate carrier isoform 2-citrin-deficiency aged 1-10 years, for whom tests showed normal liver function. Despite normal plasma ammonia levels, the affected children showed higher blood levels of ornithine (p<0.001) and citrulline (p<0.01)--amino acids involved in the urea cycle--than healthy children. Blood levels of nitrite/nitrate, metabolites of nitric oxide (NO), and asymmetric dimethylarginine inhibiting NO production from arginine were not different between these two groups. Blood glucose, galactose, pyruvate, and lactate levels after 4-5h fasting were not different between these groups, but the affected group showed a significantly higher lactate to pyruvate ratio. Low-density and high-density lipoprotein cholesterol levels in the affected group were 1.5 times higher than those in the controls. Plasma oxidized low-density lipoprotein apparently increased in the affected children; their levels of urinary oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine and acrolein-lysine were significantly higher than those in the controls. Results of this study showed, even during the silent period, sustained hypercitrullinemia, hypercholesterolemia, and augmented oxidative stress in children with citrin deficiency.

Clinical Relevance of Ceramide Metabolism in the Pathogenesis of Human Head and Neck Squamous Cell Carcinoma (HNSCC): Attenuation of C18-ceramide in HNSCC Tumors Correlates with Lymphovascular Invasion and Nodal Metastasis

PubMed Central

Karahatay, Serdar; Thomas, Kesha; Koybasi, Serap; Senkal, Can E.; ElOjeimy, Saeed; Liu, Xiang; Bielawski, Jacek; Day, Terry A.; Boyd Gillespie, M; Sinha, Debajyoti; Norris, James S.; Hannun, Yusuf A.; Ogretmen, Besim

2007-01-01

It has been documented previously that defects in the generation of C18-ceramide, a product of ceramide synthase 1 (CerS1), also known as longevity assurance gene 1 (hLASS1), play important roles in the pathogenesis and/or progression of HNSCC. However, whether altered levels of ceramide generation in HNSCC tumors have any clinical relevance remains unknown. In this study, the levels of endogenous ceramides were measured in tumor tissues of 45 HNSCC patients as compared to their normal tissues using high-pressure liquid chromatography/mass spectrometry (LC/MS), and then possible link between ceramide levels and the clinical parameters of HNSCC were examined. The data showed that the levels of C16-, C24-, C24:1-ceramide were significantly elevated in the majority of tumor tissues compared to their normal tissues, while the levels of only C18-ceramide were significantly decreased in HNSCC tumors, especially in tumor tissues of male patients. Importantly, it was also shown here that decreased C18-ceramide levels in HNSCC tumor tissues were significantly associated with the higher incidences of lymphovascular invasion, and pathologic nodal metastasis. Importantly, attenuation of C18-ceramide was also positively linked to the higher overall stages of the primary HNSCC tumors. Therefore, these data suggest, for the first time, that the defects in the generation/accumulation of C18-ceramide might have important clinical roles in HNSCC, especially in lymphovascular invasion and nodal disease. PMID:17619081

Erythropoiesis and erythropoietin in hypo- and hyperthyroidism.

PubMed

Das, K C; Mukherjee, M; Sarkar, T K; Dash, R J; Rastogi, G K

1975-02-01

Qualitative and quantitative studies of erythropoiesis in 23 patients with hypothyroidism and 21 patients with hyperthryoidism included routine hematologic evaluation, bone marrow morphology, status of serum iron, B12 and folate red blood cell mass and plasma volume by radioisotope methods, erythrokinetics and radiobioassay of plasma erythropoietin. A majority of patients with the hypothyroid state had significant reduction in red blood cell mas per kg of body weight. The presence of anemia in many of these patients was not evident from hemoglobin and hematocrit values due to concomitant reduction of plasma volume. The erythrokinetic data in hypothyroid patients provided evidence of significant decline of the erythropoietic activity of the bone marrow. Erythroid cells in the marrow were depleted and also showed reduced proliferative activity as indicated by lower 3H-thymidine labeling index. Plasma erythropoietin levels were reduced, often being immeasurable by the polycythemic mouse bioassay technique. These changes in erythropoiesis in the hypothyroid state appear to be a part of physiological adjustment to the reduced oxygen requirement of the tissues due to diminished basal metabolic rate. Similar investigations revealed mild erythrocytosis in a significant proportion of patients with hyperthyroidism. Failure of erythrocytosis to occur in other patients of this group was associated with impaired erythropoiesis due to a deficiency of hemopoietic nutrients such as iron, vitamin B12 and folate. The mean plasma erythropoietin level of these patients was significantly elevated; in 4 patients the levels were in the upper normal range whereas in the rest, the values were above the normal range. The bone marrow showed erythyroid hyperplasia in all patients with hyperthyroidism. The mean 3H-thymidine labeling index of the erythroblasts was also significantly higher than normal in hyperthyroidism; in 8 patients the index was within the normal range whereas in the remaining 13 it was above the normal range. Erythrokinetic studies also provided evidences of increased erythropoietic activity in the bone marrow. It is postulated that thyroid hormones stimulate erythropoiesis, sometimes leading to erythrocytosis provided there is no deficiency of hemopoietic nutrients. Stimulation of erythropoiesis by thryoid hormones appears to be mediated through erythropoietin.

The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

PubMed Central

Ryan, James; Curran, Catherine E.; Hennessy, Emer; Newell, John; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M.

2011-01-01

Introduction The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, p<0.05). Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05) and RARα (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r = −0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6–16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16–26 fold). Conclusion Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones. PMID:21283523

Ischemic acute renal failure and antioxidant therapy in the rat. The relation between glomerular and tubular dysfunction.

PubMed Central

Bird, J E; Milhoan, K; Wilson, C B; Young, S G; Mundy, C A; Parthasarathy, S; Blantz, R C

1988-01-01

The effects of antioxidant therapy with probucol were evaluated in rats subjected to 1 h renal ischemia and to 24 h reperfusion. Probucol exerted significant antioxidant effects in renal cortical tubules in vitro when exposed to a catalase-resistant oxidant. At 24 h probucol treatment (IP) improved single nephron glomerular filtration rate (SNGFR) (28.1 +/- 3.3 nl/min) in comparison to untreated ischemic (I) rats (15.2 +/- 3.0), primarily as a result of improving SNGFR in a population of low SNGFR, low flow and/or obstructed nephrons. However, absolute proximal reabsorption remained abnormally low in IP rats at 24 h (5.9 +/- 0.8 nl/min), and cell necrosis was greater than in I rats. Kidney GFR remained low in IP rats due to extensive tubular backleak of inulin measured by microinjection studies. Evaluations after 2 h of reperfusion revealed a higher SNGFR in IP (36 +/- 3.1 nl/min) than I rats (20.8 +/- 2.7 nl/min). Absolute proximal reabsorption was essentially normal (11.6 +/- 1.3 nl/min) in IP rats, which was higher than IP rats at 24 h and the concurrent I rats. Administration of the lipophilic antioxidant, probucol, increased SNGFR and proximal tubular reabsorption within 2 h after ischemic renal failure. Although SNGFR remained higher than I rats at 24 h, absolute reabsorption fell below normal levels and tubular necrosis was more extensive in IP rats. Early improvement in nephron filtration with antioxidants may increase load dependent metabolic demand upon tubules and increase the extent of damage and transport dysfunction. Images PMID:2835399

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

PubMed

Oto, Yuji; Matsubara, Keiko; Ayabe, Tadayuki; Shiraishi, Masahisa; Murakami, Nobuyuki; Ihara, Hiroshi; Matsubara, Tomoyo; Nagai, Toshiro

2018-06-01

Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2-23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3-48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7-30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis. © 2018 Wiley Periodicals, Inc.

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 2. Tissue biochemistry evaluation.

PubMed

Lohner, T W; Reash, R J; Williams, M

2001-11-01

Sunfish were collected from a fly ash pond-receiving stream and an Ohio River reference site to assess biochemical responses to coal ash effluent exposure. Selenium levels in sunfish from the receiving stream were higher than toxic thresholds associated with adverse population effects and reproductive impairment. Tissue biochemistry was found to be indicative of metal exposure and effect, but varied widely. Liver glycogen was positively correlated with increased liver metal levels, indicating no adverse effect upon stored carbohydrate levels. Lipid levels decreased with increasing metals, indicating possible nutritional stress. Protein levels increased with increasing metal levels, possibly due to the synthesis of proteins to sequester the metals. ATPase, dUTPase, and alkaline phosphatase activity generally decreased with exposure to ash pond metals, but remained within normal physiological ranges. Fish condition factors and liver somatic indices were correlated with liver lipid levels, dUTPase activity, and gill ATPase and alkaline phosphatase activity. Exposure to coal ash effluents produced biochemical markers of exposure that were associated with fish condition indicators; however, the indices themselves were not significantly affected by effluent exposure.

Coral and mollusc resistance to ocean acidification adversely affected by warming

NASA Astrophysics Data System (ADS)

Rodolfo-Metalpa, R.; Houlbrèque, F.; Tambutté, É.; Boisson, F.; Baggini, C.; Patti, F. P.; Jeffree, R.; Fine, M.; Foggo, A.; Gattuso, J.-P.; Hall-Spencer, J. M.

2011-09-01

Increasing atmospheric carbon dioxide (CO2) concentrations are expectedto decrease surface ocean pH by 0.3-0.5 units by 2100 (refs , ), lowering the carbonate ion concentration of surfacewaters. This rapid acidification is predicted to dramatically decrease calcification in many marine organisms. Reduced skeletal growth under increased CO2 levels has already been shown for corals, molluscs and many other marine organisms. The impact of acidification on the ability of individual species to calcify has remained elusive, however, as measuring net calcification fails to disentangle the relative contributions of gross calcification and dissolution rates on growth. Here, we show that corals and molluscs transplanted along gradients of carbonate saturation state at Mediterranean CO2 vents are able to calcify and grow at even faster than normal rates when exposed to the high CO2 levels projected for the next 300 years. Calcifiers remain at risk, however, owing to the dissolution of exposed shells and skeletons that occurs as pH levels fall. Our results show that tissues and external organic layers play a major role in protecting shells and skeletons from corrosive sea water, limiting dissolution and allowing organisms to calcify. Our combined field and laboratory results demonstrate that the adverse effects of global warming are exacerbated when high temperatures coincide with acidification.

Role of insulin resistance and adipocytokines on serum alanine aminotransferase in obese patients with type 2 diabetes mellitus.

PubMed

de Luis, D A; Aller, R; Izaola, O; Gonzalez Sagrado, M; Conde, R; de la Fuente, B

2013-01-01

The aim of our study was to study the association of insulin resistance expressed by HOMA and adipokines in obese type 2 diabetic patients with or without hyper-transaminasemia. A population of 72 obese patients with type 2 diabetes mellitus was analyzed. HOMA-IR was calculated as indicator of insulin-resistance. Adipocytokines blood levels were measured. Patients were classified as group I (n=37) when serum ALT activity was normal or group II (NAFLD patients: n=35) when serum ALT activity was greater than the median value of the group (≥ 28 UI/L). In NAFLD group, BMI, weight, fat mass, waist to hip ratio, waist circumference, triglycerides, HOMA and insulin levels were higher than control group. In the logistic regression analysis with a dependent variable (ALT) and the statistical univariant variables as independent variables, the HOMA-IR remained in the model, with an Odd's ratio of 1.21 (CI:95%: 1.11-1.35) to have a high ALT level with each 1 unit of HOMA-IR adjusted by age, sex, weight, and dietary intake. Some metabolic parameters are associated with elevated ALT in female obese patients. However, adjusted by other variables, only insulin resistance remained associated.

Measuring mitochondrial uncoupling protein-2 level and activity in insulinoma cells.

PubMed

Barlow, Jonathan; Hirschberg, Verena; Brand, Martin D; Affourtit, Charles

2013-01-01

Mitochondrial uncoupling protein-2 (UCP2) regulates glucose-stimulated insulin secretion (GSIS) by pancreatic beta cells-the physiological role of the beta cell UCP2 remains a subject of debate. Experimental studies informing this debate benefit from reliable measurements of UCP2 protein level and activity. In this chapter, we describe how UCP2 protein can be detected in INS-1 insulinoma cells and how it can be knocked down by RNA interference. We demonstrate briefly that UCP2 knockdown lowers glucose-induced rises in mitochondrial respiratory activity, coupling efficiency of oxidative phosphorylation, levels of mitochondrial reactive oxygen species, and insulin secretion. We provide protocols for the detection of the respective UCP2 phenotypes, which are indirect, but invaluable measures of UCP2 activity. We also introduce a convenient method to normalize cellular respiration to cell density allowing measurement of UCP2 effects on specific mitochondrial oxygen consumption. Copyright © 2013 Elsevier Inc. All rights reserved.

Plasma adiponectin levels and incident glucose intolerance in Japanese-Brazilians: a seven-year follow-up study.

PubMed

Vendramini, Marcio F; Ferreira, Sandra R G; Gimeno, Suely G A; Kasamatsu, Teresa S; Miranda, Walkiria L; Moisés, Regina S

2006-09-01

The objective of this study was to investigate whether decreased baseline adiponectin levels are an independent risk factor for development of glucose intolerance in a population-based study of Japanese-Brazilians, a group with one of the highest prevalence rates of diabetes worldwide. We examined 210 Japanese-Brazilians (97 male and 113 female, aged 56.7+/-10.1 years) with normal glucose tolerance (NGT). Plasma adiponectin, insulin, fasting and 2-h plasma glucose and lipid profile were evaluated at baseline and also at 7-year follow-up. Plasma adiponectin levels were significantly lower in glucose intolerance progressors compared with subjects who remained NGT. By increasing tertiles of adiponectin, the frequencies of subjects who progressed to glucose intolerance were 40%, 33% and 27% and the frequencies of subjects who remained NGT were 13%, 35% and 52% (chi2=15.8, p=0.001). Logistic regression analyses showed that adiponectin levels (OR for the highest versus lowest tertile: 0.31; 95% CI: 0.12-0.84, p=0.021), male sex (OR: 2.61, 95% CI: 1.21-5.65, p=0.015), fasting plasma glucose (0R: 3.05, 95% CI: 1.35-6.91, p=0.008) and waist circumference (OR: 1.04, 95% CI: 1.00-1.08, p=0.046) were independent risk factors for the progression to glucose intolerance. In conclusion, low plasma levels of adiponectin is one of several independent predictors of glucose intolerance in a Japanese-Brazilian population.

Overexpression of vasopressin (V3) and corticotrophin-releasing hormone receptor genes in corticotroph tumours.

PubMed

de Keyzer, Y; René, P; Beldjord, C; Lenne, F; Bertagna, X

1998-10-01

The molecular mechanisms underlying ACTH-secreting tumour formation remain unknown. Transmembrane signalling pathways play an important role in several endocrine disorders including pituitary tumours. To investigate the role of the pituitary vasopressin (V3) receptor (R) in ACTH-secreting tumours we have qualitatively and quantitatively analysed its mRNA. RT-PCR, denaturing gradient gel electrophoresis and S1 nuclease protection experiments were used to analyse V3 mRNA structure in ACTH-secreting tumours. We also developed a competitive RT-PCR system to compare the levels of expression of POMC, V3 and CRH-R genes. This system used as competitor a single mutant template (termed multi-mutant) containing primers for the three genes flanking an unrelated core sequence allowing multiple quantifications from the same cDNA preparations. We analysed 12 normal pituitaries, 15 corticotroph pituitary adenomas and 6 ACTH-secreting bronchial carcinoids. The V3 mRNA structure and sequence were found to be identical in normal and tumoural pituitary indicating that the tumoural Vs mRNA codes for a normal receptor. POMC RT-PCR signals in the pituitary tumour group were approximately 7-fold higher than in the normal pituitary group. Similarly, V3 and CRH-R signal were increased in pituitary tumors (mean +/- SEM: 5.87 x 10(-6) +/- 1.73 x 10(-6), and 2.33 x 10(-4) +/- 1.4 x 10(-4), respectively), when compared to normal pituitaries (1.19 x 10(-7) +/- 2.39 x 10(-8), and 1.7 x 10(-6) +/- 4.65 x 10(-7), respectively) suggesting that these two genes are expressed at very high levels in corticotroph tumours. When expressed relative to the corresponding POMC signals, increases in V3 and CRH-R signals reached 49-fold and 137-fold, respectively, in pituitary tumours. In ACTH-secreting bronchial carcinoids V3 gene expression level was also higher than in normal pituitary, whereas CRH-R signals were detected in only 4 of the 6 tumours with wide variations. Our results show that both vasopressin and CRH receptor genes are overexpressed in ACTH-secreting pituitary tumours. They suggest that overexpression of G protein-coupled receptors may be an additional mechanism through which membrane receptors may play a role in human tumours.

Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

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

Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.

2015-04-01

Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulsemore » amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2 and miRNAs are subnormal, ubiquitination is elevated but JAK2/STAT5b is normal.« less

Microbial flora of tears of orthokeratology patients, and microbial contamination of contact lenses and contact lens accessories.

PubMed

Boost, Maureen V; Cho, Pauline

2005-06-01

The purpose of this study is to determine if there are changes in the ocular flora of overnight orthokeratology (ortho-k) patients, and the levels of contamination of their lenses and lens accessories, and to correlate compliance with levels of contamination. Normal ocular flora of 41 subjects was determined twice before commencing ortho-k lens wear by culture of the lower conjunctiva. Further specimens were collected on six follow-up visits after beginning lens wear, as were samples from their lenses, cases, and suction holders. A questionnaire on lens care was administered after the fifth visit. Three subjects provided conjunctival samples yielding Staphylococcus aureus on one occasion before lens wear, one being positive for this organism after beginning lens wear. Of 38 subjects yielding no growth or only normal eye flora before use, 28 remained free of ocular pathogens after beginning lens wear. Only four subjects had positive cultures on more than one occasion after lens wear. There was no significant difference in isolation levels of pathogens with lens wear (p = 0.423). Lens culture of 54% of subjects yielded no growth or normal flora only; lenses of 16 subjects yielded potential pathogens, including three subjects contaminated on more than one occasion. Lens isolates did not match the organisms transiently colonizing the eye. Lens case, the most frequently contaminated item, was associated with lens contamination (p < 0.001), the same organism being isolated from both items in 11 subjects. Lens suction holder was less frequently contaminated. Neither lens case nor suction holder contamination was associated with isolates from the eye. Reported good compliance correlated with lack of contamination in all but one subject. The most frequent breaches in the lens care protocol were failure to clean, disinfect, and replace the lens case. Ocular flora was not altered by ortho-k lens wear over an extended period, and patients remained free of infection. Contaminants identified were generally of a transient nature. Most patients had significant contamination of at least one item, most frequently the lens case. Lens case isolates were significantly associated with those from the lens. The majority of patients reporting good compliance had low or no contamination of their lenses and accessories.

[A case of dwarfism with severely reduced activity of growth hormone-binding protein].

PubMed

Igarashi, N; Sato, T

1991-10-20

We presented a 16-year-old boy with severe growth retardation and markedly decreased levels of growth hormone-binding protein (GHBP) in plasma, which was shown to correspond to the extracellular composition of hepatic GH receptor and suggested to reflect tissue concentration of the receptor. His height was 92.5 cm (-13.5 SD), the weight 9.6kg (-5.8 SD) and Tanner stage was I. His bone age was 3.5 years old at 16 years of age. Karyotype was 46,XY and thyroid function was normal. SM-C levels, determined by Nichols RIA using unextracted plasma, were within the low normal range, 0.67/0.68U/ml. In contrast, using a method of acid-ethanol extraction, IGF-I and IGF-II levels were definitely low, 29ng/ml (normal 88-240) and 165ng/ml (374-804) respectively. GH responses in various provocation tests, including insulin, arginine and GRF, were within normal. Basal GH levels were 20 +/- 12ng/ml and urinary GH excretion rates 217 +/- 85pg/mg. Cr, which were elevated compared to age-matched control. Molecular size of his circulating GH was similar to control subjects. The biological activities of GH, evaluated by radioreceptor assay and Nb2 cell bioassay, were proportional to the immunoactivities of GH. SM bioactivities, which were determined by the stimulatory effects on DNA synthesis of rabbit costal chondrocytes and human fibroblasts, were apparently reduced. Electrophoretic patterns of IGF-binding protein was similar to those of GH deficient cases. Daily administration of hGH (4U/day) for 5 days resulted in a poor response of SM-C production (before 0.68, after 0.77U/ml). GHBP activities were definitely low by gel-filtration, immunoprecipitation and charcoal methods, as seen in Laron dwarfism which is defined as a syndrome of congenital GH receptor defects. These results indicate that the tissue content of GH receptor in this case was quantitatively reduced and as a result, he showed a resistance to endogenous and exogenous GH. It remains to be elucidated whether the GH receptor defect in our case is derived from a genetic origin or an acquired condition.

Retrospective study of salazosulfapyridine in eight patients with rheumatoid arthritis on hemodialysis.

PubMed

Akiyama, Yuji; Sakurai, Yusei; Kato, Yuji; Furuta, Eiichi; Mimura, Toshihide

2014-03-01

We examined the pharmacokinetics (PK) of salazosulfapyridine (SASP) and its metabolite, sulfapyridine (SP), as well as the influence of hemodialysis (HD), and investigated the utility of consecutive administration of SASP in rheumatoid arthritis patients undergoing HD. The PK of salazosulfapyridine and SP in serum samples from 8 patients was determined using high-performance liquid chromatography. When SASP 500 mg was administered, the area under curve for serum concentration of SASP was similar to that seen with normal subjects in the Phase I study. The maximum serum concentration of SP was significantly higher than that in normal subjects, but was far from the danger level. SASP was not dialyzed, whereas on average 62% of SP was dialyzed. Following 5 consecutive days of administration of SASP, serum levels of SASP and SP on day 5 were rather higher than those on day 1, although both remained within the safe range. SASP administration from four months to three years in seven subjects resulted in four American College of Rheumatology 20 improvement criteria (57.1%), with one developing a rash. If SASP is initiated at a low dosage (≤ 500 mg) and increased up to 1000 mg under careful monitoring, it is safe for HD patients.

microRNA-497 overexpression decreases proliferation, migration and invasion of human retinoblastoma cells via targeting vascular endothelial growth factor A

PubMed Central

Li, Jianjun; Zhang, Yinghui; Wang, Xiuchao; Zhao, Ruibo

2017-01-01

The expression level and roles of microRNA-497 (miR-497) have been frequently reported in previous studies on cancer. However, its expression, function and associated molecular mechanisms in retinoblastoma remain unknown. In the present study, miR-497 expression levels in human retinoblastoma tissues, normal retinal tissues and retinoblastoma cell lines were determined using reverse transcription-quantitative polymerase chain reaction. In addition, a Cell Counting Kit-8 assay, cell migration assay, cell invasion assay, western blot analysis and Dual-Luciferase reporter assay were used to explore the expression, functions and molecular mechanisms of miR-497 in human retinoblastoma. It was demonstrated that miR-497 was significantly downregulated in retinoblastoma tissues and cell lines compared with normal retinal tissues. Ectopic expression of miR-497 decreased the proliferation, migration and invasion of retinoblastoma cells. Furthermore, VEGFA was verified as a potential direct target of miR-497 in vitro. Taken together, the results indicate that miR-497 functions as a tumor suppressor in the carcinogenesis and progression of retinoblastoma via targeting VEGFA. miR-497 should be investigated as a potential therapeutic target for the treatment of retinoblastoma. PMID:28588740

Aging is associated with altered inflammatory, arachidonic acid cascade and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex

PubMed Central

Keleshian, Vasken L.; Modi, Hiren R.; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Aging is a risk factor for Alzheimer’s disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, since DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged (41 ± 1 (SEM) years) and ten aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of BDNF, CREB, and synaptophysin and hypomethylation of BAX. These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated. PMID:23336521

A global quantification of "normal" sleep schedules using smartphone data.

PubMed

Walch, Olivia J; Cochran, Amy; Forger, Daniel B

2016-05-01

The influence of the circadian clock on sleep scheduling has been studied extensively in the laboratory; however, the effects of society on sleep remain largely unquantified. We show how a smartphone app that we have developed, ENTRAIN, accurately collects data on sleep habits around the world. Through mathematical modeling and statistics, we find that social pressures weaken and/or conceal biological drives in the evening, leading individuals to delay their bedtime and shorten their sleep. A country's average bedtime, but not average wake time, predicts sleep duration. We further show that mathematical models based on controlled laboratory experiments predict qualitative trends in sunrise, sunset, and light level; however, these effects are attenuated in the real world around bedtime. Additionally, we find that women schedule more sleep than men and that users reporting that they are typically exposed to outdoor light go to sleep earlier and sleep more than those reporting indoor light. Finally, we find that age is the primary determinant of sleep timing, and that age plays an important role in the variability of population-level sleep habits. This work better defines and personalizes "normal" sleep, produces hypotheses for future testing in the laboratory, and suggests important ways to counteract the global sleep crisis.

Expression and significance of CHIP in canine mammary gland tumors

PubMed Central

WANG, Huanan; YANG, Xu; JIN, Yipeng; PEI, Shimin; ZHANG, Di; MA, Wen; HUANG, Jian; QIU, Hengbin; ZHANG, Xinke; JIANG, Qiuyue; SUN, Weidong; ZHANG, Hong; LIN, Degui

2015-01-01

CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy. PMID:26156079

[Results of a dynamic study on the status of health and nutrition of a Siberian vegan settlement].

PubMed

Medkova, I L; Mosiakina, L I; Biriukova, L S

2001-01-01

In 1996 for the first time a study of state of health, living conditions and nutrition status of 84 persons from the Siberian settlement of the rigorous vegetarians--vegans and 26 aboriginal inhabitants who feed on a traditional mixed diet was carried out. The clinical and laboratory investigations are kept. The positive influencing vegan ration on a serum lipids, body weight, state of cardiovascular system was showed. The contents of vitamin B12 and serum iron in vegans was in normal physiological range. The level of blood calcium was reduced in comparison with control. Increased contents of copper and zinc in blood was marked both in vegans and in control group. The repeated examination of 77 vegans of the same settlement in 1999 has revealed positive alterations in serum lipids: augmentation of cholesterol of high density lipoproteins on the average on 54.3%, that result in a reliable decrease of atherogenicity coefficient. The decrease to normal amounts of blood copper and zinc, and also increase of blood calcium on the average on 16% was marked. However level of calcium remained below than physiological values.

Effects of the whole-body cryotherapy on NTproBNP, hsCRP and troponin I in athletes.

PubMed

Banfi, Giuseppe; Melegati, Gianluca; Barassi, Alessandra; d'Eril, Gianlodovico Melzi

2009-11-01

Whole-body cryotherapy refers to brief exposure to very cold air for treating symptoms of various illnesses. In sports medicine, whole-body cryotherapy is administered to improve recovery from muscular trauma. As specific studies are lacking, we measured cardiac markers in 10 top-level rugby players of the Italian National team before and after a 1-week course of daily sessions of whole-body cryotherapy. All subjects continued with the same training workload as that of the previous weeks. N-terminal pro B-type natriuretic peptide (NTproBNP) levels increased but remained within the normal range, whilst troponin I (TnI) and high sensitivity C-reactive protein (hsCRP) were unchanged. Whole-body cryotherapy did not impair cardiac function in this sample of elite athletes.

[Subclinical hyperthyroidism: from diagnosis to treatment].

PubMed

Corvilain, B

2012-09-01

Subclinical hyperthyroidism is a common clinical entity. Subclinical hyperthyroidism is defined as a serum TSH below the reference range but a normal T4 and T3 level in an asymptomatic patient. Whether or not subclinical hyperthyroidism should be treated remains a matter of debate. Cross-sectional studies and longitudinal population-based studies demonstrate association between subclinical hyperthyroidism and risk of atrial fibrillation, osteoporosis and cardiovascular and global mortality. However, there are no randomized clinical trials answering the question whether long term-health outcomes are improved by the treatment of subclinical hyperthyroidism. Therefore in the absence of evidence for or against treatment of subclinical hyperthyroidism, it seems appropriate to follow algorithms that consider the level of TSH and the presence of risks factors (age > 65 years, osteoporosis, post menopause and cardiac disease).

Metabolic studies with NMR spectroscopy of the alga Dunaliella salina trapped within agarose beads.

PubMed

Bental, M; Pick, U; Avron, M; Degani, H

1990-02-22

A technique for the entrapment of the unicellular algae Dunaliella salina in agarose beads and their perfusion during NMR measurements is presented. The trapped cells maintained their ability to proliferate under normal growth conditions, and remained viable and stable under steady-state conditions for long periods during NMR measurements. Following osmotic shock in the dark, prominent changes were observed in the intracellular level of ATP and polyphosphates, but little to no changes in the intracellular pH or orthoposphate content. When cells were subjected to hyperosmotic shock, the ATP level decreased. The content of NMR-visible polyphosphates decreased as well, presumably due to the production of longer, NMR-invisible structures. Following hypoosmotic shock, the ATP content increased and longer polyphosphates were broken down to shorter, more mobile polymers.

Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat.

PubMed

Lansdown, A B; Sampson, B; Laupattarakasem, P; Vuttivirojana, A

1997-11-01

Incisional wounds 15 mm long were induced surgically in the back skin of young adult Wistar rats. They were sutured and used as an experimental model in the therapeutic evaluation of daily applications of 0.5 mL of silver nitrate (SN) at 0.01, 0.1 or 1.0% w/v aqueous solution, or 0.5 g silver sulphadiazine (SSD) over a 10-day period. Control wounds received deionized water only. The silver preparations were not toxic but SN did stain the hair and superficial layers of the stratum corneum. The wounds remained microbiologically clean. Wounds exposed to SN (0.1 or 1.0%) or SSD healed more rapidly than controls. From about the fourth day of treatment, we noted a more rapid exteriorization of sutures, improved wound closure and an earlier loss of scabs and wound debris. Silver treatment appeared to reduce the inflammatory and granulation tissue phases of healing and enhance epidermal repair. Silver from SN was deposited as silver sulphide in extrafollicular hair shafts and superficial aspects of the skin and wound debris but not at deeper levels. Silver uptake was four-fold higher in damaged skin than in intact tissue. SSD was absorbed by intact and wounded skin but the silver did not precipitate as silver sulphide and its localization in the tissue is not known. Uptake of silver from SN or SSD was associated with changes in the concentrations of zinc and calcium in the skin. Zinc levels were depressed during the inflammatory and proliferative phases of healing and then increased. Zinc concentrations had normalized by 10 days when wound healing was achieved. Calcium levels remained higher than normal throughout the observation period. The mechanism of action of silver in advancing wound healing in the rat is unclear. Its ability to reduce the inflammatory and granulation phases of healing, and to invoke metallothionein production and influence metal ion binding are possibly important.

Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura

PubMed Central

Becerra, E; Scully, M A; Leandro, M J; Heelas, E O; Westwood, J-P; De La Torre, I; Cambridge, G

2015-01-01

Autoantibodies inhibiting the activity of the metalloproteinase, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), underlie the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Rituximab (RTX) combined with plasma-exchange (PEX) is an effective treatment in TTP. Patients can remain in remission for extended periods following PEX/RTX, and this is associated with continuing reduction in antibodies to ADAMTS13. Factors controlling B cell differentiation to autoantibody production, including stimulation through the B cell receptor and interactions with the B cell-activating factor (BAFF), may thus impact length of remission. In this cross-sectional study, we measured naive and memory B cell phenotypes [using CD19/immunoglobulin (Ig)D/CD27] following PEX/RTX treatment in TTP patients at B cell return (n = 6) and in 12 patients in remission 10–68 months post-RTX. We also investigated relationships among serum BAFF, soluble CD23 (sCD23– a surrogate measure of acquiring B memory (CD27+) phenotype) and BAFF receptor (BAFF-R) expression. At B cell return after PEX/RTX, naive B cells predominated and BAFF-R expression was reduced compared to healthy controls (P < 0·001). In the remission group, despite numbers of CD19+ B cells within normal limits in most patients, the percentage and absolute numbers of pre-switch and memory B cells remained low, with sCD23 levels at the lower end of the normal range. BAFF levels were correlated inversely with BAFF-R expression and time after therapy. In conclusion, the long-term effects of RTX therapy in patients with TTP included slow regeneration of memory B cell subsets and persistently reduced BAFF-R expression across all B cell subpopulations. This may reflect the delay in selection and differentiation of potentially autoreactive (ADAMTS13-specific) B cells, resulting in relatively long periods of low disease activity after therapy. PMID:25339550

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas

PubMed Central

Ibáñez-Costa, Alejandro; López-Sánchez, Laura M.; Gahete, Manuel D.; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C.; Gálvez, María A.; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J.; Maraver-Selfa, Silvia; Japón, Miguel A.; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Webb, Susan M.; Kineman, Rhonda D.; Culler, Michael D.; Castaño, Justo P.; Luque, Raúl M.

2017-01-01

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

PubMed

Ibáñez-Costa, Alejandro; López-Sánchez, Laura M; Gahete, Manuel D; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gálvez, María A; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J; Maraver-Selfa, Silvia; Japón, Miguel A; García-Arnés, Juan A; Soto-Moreno, Alfonso; Webb, Susan M; Kineman, Rhonda D; Culler, Michael D; Castaño, Justo P; Luque, Raúl M

2017-02-09

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D 2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca 2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca 2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca 2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca 2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D 2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D 2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis.

PubMed

Lansey, Melissa N; Walker, Natalie N; Hargett, Stefan R; Stevens, Joseph R; Keller, Susanna R

2012-11-15

Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We observed increased and normal basal glucose uptake in isolated AS160(-/-) adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis.

Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea.

PubMed

Carmina, Enrico; Fruzzetti, Franca; Lobo, Roger A

2016-06-01

Functional hypothalamic amenorrhea is a disorder characterized by cessation of menstrual cycles in the absence of organic disease. In most patients, it occurs in adult life after a stressful event and may be related to a condition of mild chronic energy deprivation. The endocrine pattern is characterized by low estrogen levels with an absent response to a progestogen challenge test and low-normal gonadotropin levels. A few studies have shown that some of these women may have some features of polycystic ovary syndrome; these features include an increased androgen response to gonadotropins, increased anti-Mullerian hormone levels, and altered ovarian morphology or increased ovarian size. These findings suggest a link between these 2 completely different disorders: functional hypothalamic amenorrhea and polycystic ovary syndrome. The importance of the possible coexistence of these disorders in some women is important for follow-up of these women and in their treatment if they desire to become pregnant. To determine whether a subgroup of well-characterized women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Retrospective analysis of women with functional hypothalamic amenorrhea. Forty consecutive patients and 28 normal age-matched control patients were studied. Blood was obtained for serum anti-Mullerian hormone, androgens, and other hormone levels and all women had ovarian ultrasonographic measurements. In the entire group of women with functional hypothalamic amenorrhea, anti-Mullerian hormone and ovarian volume were greater than in control patients. In 13 patients (32.5%), anti-Mullerian hormone was elevated (>4.7 ng/mL, levels consistent with polycystic ovary syndrome) and in this group, ovarian volume was significantly greater than in the remaining patients with functional hypothalamic amenorrhea. Four of the 13 women with functional hypothalamic amenorrhea who had elevated anti-Mullerian hormone levels (10%), also had ovarian volume ≥10 cc (consistent with polycystic ovarian syndrome). In these patients all studied androgens were in the upper normal range or slightly elevated despite low-normal gonadotropins; mean total testosterone was significantly greater than in the other patients with increased anti-Mullerian hormone values with normal ovarian size (P<.05.) Six other women with functional hypothalamic amenorrhea who had increased anti-Mullerian hormone also had isolated elevations of some androgen levels, but mean testosterone and ovarian size were normal. As many as 10% of women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Because no signs or symptoms of this disorder were reported by these women before the appearance of the amenorrhea, it does not seem to be a coincidental relationship. The possibility that functional hypothalamic amenorrhea favors the appearance of polycystic ovary syndrome or more likely, that a mild (ovulatory) phenotype of polycystic ovary syndrome predisposes to the development of functional hypothalamic amenorrhea should be considered. Possible mechanisms are unclear and need to be investigated but may involve common vulnerabilities such as psychologic and mood disturbances. Copyright © 2016 Elsevier Inc. All rights reserved.

Nontraditional risk factors for cardiovascular disease and visceral adiposity index among different body size phenotypes.

PubMed

Du, T; Zhang, J; Yuan, G; Zhang, M; Zhou, X; Liu, Z; Sun, X; Yu, X

2015-01-01

Increased cardiovascular disease and mortality risk in metabolically healthy obese (MHO) individuals remain highly controversial. Several studies suggested risk while others do not. The traditional cardiovascular risk factors may be insufficient to demonstrate the complete range of metabolic abnormalities in MHO individuals. Hence, we aimed to compare the prevalence of elevated lipoprotein (a), apolipoprotein B, and uric acid (UA) levels, apolipoprotein B/apolipoprotein A1 ratio, and visceral adiposity index (VAI) scores, and low apolipoprotein A1 levels among 6 body size phenotypes (normal weight with and without metabolic abnormalities, overweight with and without metabolic abnormalities, and obese with or without metabolic abnormalities). We conducted a cross-sectional analysis of 7765 Chinese adults using data from the nationwide China Health and Nutrition Survey 2009. MHO persons had intermediate prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low apolipoprotein A1 levels between metabolically healthy normal-weight (MHNW) and metabolically abnormal obese individuals (P < 0.001 for all comparisons). Elevated apolipoprotein B and UA concentrations, apolipoprotein B/apolipoprotein A1 ratio, and VAI scores were all strongly associated with the MHO phenotype (all P < 0.01). Prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low levels of apolipoprotein A1 was higher among MHO persons than among MHNW individuals. The elevated levels of the nontraditional risk factors and VAI scores in MHO persons could contribute to the increased cardiovascular disease risk observed in long-term studies. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of cyclosporin on the collagenolytic activity of gingival fibroblasts.

PubMed

Hyland, Paula L; Traynor, Patrick S; Myrillas, Theofilos T; Marley, John J; Linden, Gerard J; Winter, Paul; Leadbetter, Nicola; Cawston, Timothy E; Irwin, Chris R

2003-04-01

The immunosuppressive agent cyclosporin is associated with a number of major side-effects including the development of gingival overgrowth. Although the pathogenesis of cyclosporin-induced gingival overgrowth remains unclear, it has been suggested that the finely regulated balance between extracellular matrix synthesis and degradation may be disturbed, resulting in an accumulation of excess connective tissue components within the gingival tissue. The aim of this study was to investigate the effect of cyclosporin on matrix metalloproteinases (MMP)-1 and tissue inhibitors of MMP (TIMP)-1 expression at the mRNA, protein, and enzyme activity levels. Gingival fibroblasts were grown to confluence and then cultured in serum-free medium supplemented with cyclosporin over the concentration range of 0 to 2000 ng/ml. MMP-1 and TIMP-1 mRNA levels in cultures were determined by reverse transcription polymerase chain reaction (RT-PCR), protein levels in whole conditioned medium were assessed by enzyme-linked immunosorbent assay (ELISA), and collagenolytic activity determined using a 3H-acetylated type I collagen degradation assay. Tissue mRNA levels in normal and overgrown gingiva were also determined by RT-PCR. Results indicated that cyclosporin inhibited MMP-1 expression at both the mRNA and protein level in a dose- and time-dependent fashion. The effects on TIMP-1 expression were less clear, cyclosporin inhibiting mRNA expression, but having no effect on TIMP-1 protein levels at any concentration studied. Addition of the drug resulted in reduced levels of collagenolytic activity in the culture medium. MMP-1 mRNA expression was significantly reduced in overgrown compared to normal tissue. These results add support to the hypothesis that the accumulation of collagen seen in gingival overgrowth can be explained by a cyclosporin-induced inhibition of collagenolytic activity within the gingival tissues.

Liver Function Tests Following Irreversible Electroporation of Liver Tumors: Experience in 174 Procedures.

PubMed

Froud, Tatiana; Venkat, Shree R; Barbery, Katuzka J; Gunjan, Arora; Narayanan, Govindarajan

2015-09-01

Irreversible electroporation (IRE) is a relatively new ablation modality that uses electric currents to cause cell death. It is commonly used to treat primary and secondary liver tumors in patients with normal liver function and preexisting cirrhosis. Retrospective analysis of 205 procedures sought to evaluate changes in liver function after IRE. Liver function tests (LFTs) results before and after IRE were evaluated from 174 procedures in 124 patients. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALKP), and total bilirubin levels were analyzed. The study was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Informed consent was waived. Changes in LFT results after IRE were compared with baseline and were followed up over time to see if they resolved. Changes were compared with volume of ablation. The greatest perturbations were in transaminase levels. The levels increased sharply within 24 hours after IRE in 129 (74.1%) procedures to extreme levels (more than 20 times the upper limit of normal in one-third of cases). Resolution occurred in 95% and was demonstrated to have occurred by a mean of approximately 10 weeks, many documented as early as 7 days after procedure. ALKP levels elevated in 10% procedures, was slower to increase, and was less likely to resolve. Total bilirubin level demonstrated 2 different patterns of elevation--early and late--and similar to ALKP, it was more likely to remain elevated. There was no increased risk in patients with cirrhosis or cholangiocarcinoma. There was no correlation of levels with volume of ablation. IRE results in significant abnormalities in LFT results, but in most of the cases, these are self-limiting, do not preclude treatment, and are similar to the changes seen after radiofrequency and cryoablation in the liver. Copyright © 2015. Published by Elsevier Inc.

Normal and pathological serum levels of alpha2-macroglobulins in men and mice.

PubMed Central

Tunstall, A M; Merriman, J M; Milne, I; James, K

1975-01-01

The serum levels of alpha2-macroglobulin have been measured in normal men and mice and in a number of immunopathological conditions. Normal human concentrations are high in youth, reach their minimum in middle age, and gradually increase with old age. In all age groups the mean is higher in the female than in the male. Conversely, in normal mice the alpha2M level is low in youth, maximum in middle age, and shows a slight depression with old age, and the levels are frequently higher in males than in females; there are also strain variations. In human immunopathological conditions, there are some deviations from the normal alpha2M level but these are seen to be changes from the normal distribution of values around the mean, rather than significant elevation or depression of mean values. In some disease states studied there are differences between the sexes in the deviation from normal. "Abnormal" strains of mice had alpha2M levels within the range exhibited by "normal" mice but changes in the levels are seen in mice with various myelomas. Images PMID:47865

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

Sanders, J.E.; Buckner, C.D.; Leonard, J.M.

One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30more » had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.« less

Determination of the Threshold of Gravity for the Susceptibility to Kinetosis in Fish - a Centrifuge Experiment in the ZARM Drop-Tower employing gradually reduced Gravity

NASA Astrophysics Data System (ADS)

Anken, R.; Hilbig, R.

In the course of earlier experiments at diminished gravity conditions we have successfully used larval cichlid fish Oreochromis mossambicus as a vertebrate model system in investigating the basic cause of susceptibility to motion sickness kinetosis It was observed that most animals of a given batch reveal kinetoses i e performing looping responses LR or spinning movements SM at high quality microgravity 10-6g ZARM drop-tower whereas comparatively few individuals swim kinetotically at low quality microgravity LQM 0 03-0 05g during parabolic aircraft flights Anken and Hilbig Microgravity Sci Technol 15 52-57 2004 In order to gain further insights into a possible threshold of gravity for inducing motion sickness animals were subjected to drop-tower flights within a centrifuge The levels of gravity applied ranged from 0 009g until 0 3g The lowest level of gravity under which few normally swimming fish were observed ranged around 0 015g Since this is a very low level of gravity the normally swimming fish have to be considered to be either extremely sensitive to any force of gravity in order to use it as a cue for postural control or they use cues other than the residual gravity for maintaining equilibrium Most of the remaining kinetotically swimming animals showed LR whereas few exhibited SM With increasing gravity the ratio of normally swimming and spinning specimens increased accompanied by a decrease in the number of looping larvae Regarding the ratio a shift from LR to SM took place at around 0 02g At 0 3g all animals behaved

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio

PubMed Central

Ross, Jaime M.; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J.; Olson, Lars

2010-01-01

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes. PMID:21041631

The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet.

PubMed

Wang, Jun; Ryu, Ho Kyung

2015-10-01

The present study was conducted to investigate the effects of dried Momordica charantia aqueous extracts (MCA) and ethanol extracts (MCE) on obesity and lipid profiles in mice fed a high-fat diet. Forty two ICR mice were randomly divided into six groups. The normal group was fed a basal diet, and other groups were fed a 45% high-fat diet (HFD) for 7 weeks. The normal and HFD groups were also orally administered distilled water each day for 7 weeks. The remaining groups received Momordica charantia extract (0.5 or 1.0 g/kg/day MCA, and 0.5 or 1.0 g/kg/day MCE). In order to measure the anti-obesity and lipid profile improvement effects, body and visceral tissue weight, lipid profiles, plasma insulin levels, hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. Both MCA and MCE significantly decreased body and visceral tissue weight relative to those of the HFD group (P < 0.05). Additionally high doses of MCE and MCA significantly reduced the plasmatic insulin levels compared to the HFD groups (P < 0.05) to concentrations comparable to those found in the normal group. MCA and MCE supplementation also significantly modulated the lipid profiles in plasma, liver, and feces compared to mice fed the HFD (P < 0.05). Furthermore MCA and MCE significantly increased hepatic SOD activity, and reduced MDA generation in the liver of the HFD mice (P < 0.05). Results from the present study suggest that Momordica charantia extracts have anti-obesity effects and the ability to modulate lipid prolife of mice fed a HFD by suppressing body weight gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid peroxidation along with increasing lipid metabolism.

The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet

PubMed Central

Wang, Jun

2015-01-01

BACKGROUND/OBJECTIVES The present study was conducted to investigate the effects of dried Momordica charantia aqueous extracts (MCA) and ethanol extracts (MCE) on obesity and lipid profiles in mice fed a high-fat diet. MATERIALS/METHODS Forty two ICR mice were randomly divided into six groups. The normal group was fed a basal diet, and other groups were fed a 45% high-fat diet (HFD) for 7 weeks. The normal and HFD groups were also orally administered distilled water each day for 7 weeks. The remaining groups received Momordica charantia extract (0.5 or 1.0 g/kg/day MCA, and 0.5 or 1.0 g/kg/day MCE). In order to measure the anti-obesity and lipid profile improvement effects, body and visceral tissue weight, lipid profiles, plasma insulin levels, hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. RESULTS Both MCA and MCE significantly decreased body and visceral tissue weight relative to those of the HFD group (P < 0.05). Additionally high doses of MCE and MCA significantly reduced the plasmatic insulin levels compared to the HFD groups (P < 0.05) to concentrations comparable to those found in the normal group. MCA and MCE supplementation also significantly modulated the lipid profiles in plasma, liver, and feces compared to mice fed the HFD (P < 0.05). Furthermore MCA and MCE significantly increased hepatic SOD activity, and reduced MDA generation in the liver of the HFD mice (P < 0.05). CONCLUSIONS Results from the present study suggest that Momordica charantia extracts have anti-obesity effects and the ability to modulate lipid prolife of mice fed a HFD by suppressing body weight gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid peroxidation along with increasing lipid metabolism. PMID:26425278

Excess adiposity, inflammation, and iron-deficiency in female adolescents.

PubMed

Tussing-Humphreys, Lisa M; Liang, Huifang; Nemeth, Elizabeta; Freels, Sally; Braunschweig, Carol A

2009-02-01

Iron deficiency is more prevalent in overweight children and adolescents but the mechanisms that underlie this condition remain unclear. The purpose of this cross-sectional study was to assess the relationship between iron status and excess adiposity, inflammation, menarche, diet, physical activity, and poverty status in female adolescents included in the National Health and Nutrition Examination Survey 2003-2004 dataset. Descriptive and simple comparative statistics (t test, chi(2)) were used to assess differences between normal-weight (5th < or = body mass index [BMI] percentile <85th) and heavier-weight girls (< or = 85th percentile for BMI) for demographic, biochemical, dietary, and physical activity variables. In addition, logistic regression analyses predicting iron deficiency and linear regression predicting serum iron levels were performed. Heavier-weight girls had an increased prevalence of iron deficiency compared to those with normal weight. Dietary iron, age of and time since first menarche, poverty status, and physical activity were similar between the two groups and were not independent predictors of iron deficiency or log serum iron levels. Logistic modeling predicting iron deficiency revealed having a BMI > or = 85th percentile and for each 1 mg/dL increase in C-reactive protein the odds ratio for iron deficiency more than doubled. The best-fit linear model to predict serum iron levels included both serum transferrin receptor and C-reactive protein following log-transformation for normalization of these variables. Findings indicate that heavier-weight female adolescents are at greater risk for iron deficiency and that inflammation stemming from excess adipose tissue contributes to this phenomenon. Food and nutrition professionals should consider elevated BMI as an additional risk factor for iron deficiency in female adolescents.

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography.

PubMed

Johnston, D G; Hall, K; Kendall-Taylor, P; Ross, W M; Crombie, A L; Cook, D B; Watson, M J

1986-06-01

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

Effects and mechanisms of apolipoprotein A-V on the regulation of lipid accumulation in cardiomyocytes.

PubMed

Luo, Jun; Xu, Li; Li, Jiang; Zhao, Shuiping

2018-03-12

Apolipoprotein (apo) A-V is a key regulator of triglyceride (TG) metabolism. We investigated effects of apoA-V on lipid metabolism in cardiomyocytes in this study. We first examined whether apoA-V can be taken up by cardiomyocytes and whether low density lipoprotein receptor family members participate in this process. Next, triglyceride (TG) content and lipid droplet changes were detected at different concentrations of apoA-V in normal and lipid-accumulation cells in normal and obese animals. Finally, we tested the levels of fatty acids (FAs) taken up into cardiomyocytes and lipid secretion through [ 14 C]-oleic acid. Our results show that heart tissue has apoA-V protein, and apoA-V is taken up by cardiomyocytes. When HL-1 cells were transfected with low density lipoprotein receptor (LDLR)-related protein 1(LRP1) siRNA, apoA-V intake decreased by 53% (P<0.05), while a 37% lipid accumulation in HL-1 cells remain unchanged. ApoA-V localized to the cytoplasm and was associated with lipid droplets in HL-1 cells. A 1200 and 1800 ng/mL apoA-V intervention decreased TG content by 28% and 45% in HL-1 cells, respectively and decreased TG content by 39% in mouse heart tissue (P<0.05). However, apoA-V had no effects on TG content in either normal HL-1 cells or mice. The levels of FAs taken up into cardiomyocytes decreased by 43% (P < 0.05), and the levels of TG and cholesterol ester secretion increased by 1.2-fold and 1.6-fold, respectively (P < 0.05). ApoA-V is a novel regulator of lipid metabolism in cardiomyocytes.

Additive effect of ketoconazole and octreotide in the treatment of severe adrenocorticotropin-dependent hypercortisolism.

PubMed

Vignati, F; Loli, P

1996-08-01

Over the last few years ketoconazole and octreotide have been employed in the treatment of pituitary-dependent or ectopic Cushing's syndrome. In four patients (two men and two women, aged 25-64 yr) with severe ACTH-dependent hypercortisolism in whom medical treatment with ketoconazole showed limited effectiveness and/or tolerability, we tried the association with octreotide. In all patients ketoconazole (200-1000 mg) induced a marked decrease in urinary free cortisol (UFC) excretion, but normalization could not be achieved. After ketoconazole discontinuation, three patients received octreotide alone (300-1500 micrograms/day, sc). This drug caused a dramatic decrease in UFC excretion, although not normalization; in all patients, escape from treatment occurred. Combined treatment was carried out for 10-180 days. Urinary cortisol excretion normalized and remained steadily within normal limits in three of four patients in whom normal UFC excretion had never been attained with both single drug regimens; in the fourth patient, UFC excretion decreased to levels lower than those achieved with ketoconazole or octreotide alone. The association with octreotide allowed a reduction in the daily dose of ketoconazole in three patients. Consistent with the steady reduction of cortisol production, a striking clinical improvement occurred in all patients after starting combined treatment. The normalization of UFC in three of four patients treated with both agents suggests that this approach may be useful in the long term treatment of severe forms of hypercortisolism of both pituitary and ectopic origin. In contrast to the limited effectiveness of each drug taken singularly at the same or higher doses, the association of the two drugs had an additive effect in the attainment of normal urinary cortisol excretion.

Influence of calcium depletion on iron-binding properties of milk.

PubMed

Mittal, V A; Ellis, A; Ye, A; Das, S; Singh, H

2015-04-01

We investigated the effects of calcium depletion on the binding of iron in milk. A weakly acidic cation-exchange resin was used to remove 3 different levels (18-22, 50-55, and 68-72%) of calcium from milk. Five levels of iron (5, 10, 15, 20, and 25 mM) were added to each of these calcium-depleted milks (CDM) and the resultant milks were analyzed for particle size, microstructure, and the distribution of protein and minerals between the colloidal and soluble phases. The depletion of calcium affected the distribution of protein and minerals in normal milk. Iron added to normal milk and low-CDM (~20% calcium depletion) bound mainly to the colloidal phase (material sedimented at 100,000 × g for 1 h at 20 °C), with little effect on the integrity of the casein micelles. Depletion of ~70% of the calcium from milk resulted in almost complete disintegration of the casein micelles, as indicated by all the protein remaining in the soluble phase upon ultracentrifugation. Addition of up to ~20 mM iron to high CDM resulted in the formation of small fibrous structures that remained in the soluble phase of milk. It appeared that the iron bound to soluble (nonsedimentable) caseins in high-CDM. We observed a decrease in the aqueous phosphorus content of all milks upon iron addition, irrespective of their calcium content. We considered the interaction between aqueous phosphorus and added iron to be responsible for the high iron-binding capacity of the proteins in milk. The soluble protein-iron complexes formed in high-CDM (~70% calcium depletion) could be used as an effective iron fortificant for a range of food products because of their good solubility characteristics. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

PubMed

Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M

2013-03-01

The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

The archetypal R90C CADASIL-NOTCH3 mutation retains NOTCH3 function in vivo.

PubMed

Monet, Marie; Domenga, Valérie; Lemaire, Barbara; Souilhol, Céline; Langa, Francina; Babinet, Charles; Gridley, Thomas; Tournier-Lasserve, Elisabeth; Cohen-Tannoudji, Michel; Joutel, Anne

2007-04-15

Cerebral Autosomal Dominant Arteriopathy with Subcortical infarcts and Leukoencephalopathy (CADASIL) is the most prominent known cause of inherited stroke and vascular dementia in human adult. The disease gene, NOTCH3, encodes a transmembrane receptor primarily expressed in arterial smooth muscle cells (SMC). Pathogenic mutations lead to an odd number of cysteine residues within the NOTCH3 extracellular domain (NOTCH3(ECD)), and are associated with progressive accumulation of NOTCH3(ECD) at the SMC plasma membrane. The murine homolog, Notch3, is dispensable for viability but required post-natally for the elaboration and maintenance of arteries. How CADASIL-associated mutations impact NOTCH3 function remains a fundamental, yet unresolved issue. Particularly, whether NOTCH3(ECD) accumulation may titrate the ligand and inhibit the normal pathway is unknown. Herein, using genetic analyses in the mouse, we assessed the functional significance of an archetypal CADASIL-associated mutation (R90C), in vivo, in brain arteries. We show that transgenic mouse lines expressing either the wild-type human NOTCH3 or the mutant R90C human NOTCH3, at comparable and physiological levels, can rescue the arterial defects of Notch3-/- mice to similar degrees. In vivo assessment of NOTCH3/RBP-Jk activity provides evidence that the mutant NOTCH3 protein exhibits normal level of activity in brain arteries. Remarkably, the mutant NOTCH3 protein remains functional and does not exhibit dominant negative interfering activity, even when NOTCH3(ECD) accumulates. Collectively, these data suggest a model that invokes novel pathogenic roles for the mutant NOTCH3 protein rather than compromised NOTCH3 function as the primary determinant of the CADASIL arteriopathy.

Potential Role of Vegetarianism on Nutritional and Cardiovascular Status in Taiwanese Dialysis Patients: A Case-Control Study.

PubMed

Ou, Shih-Hsiang; Chen, Mei-Yin; Huang, Chien-Wei; Chen, Nai-Ching; Wu, Chien-Hsing; Hsu, Chih-Yang; Chou, Kang-Ju; Lee, Po-Tsang; Fang, Hua-Chang; Chen, Chien-Liang

2016-01-01

Cardiovascular disease remains the most common cause of death for patients on chronic dialysis. End stage renal disease patients undergoing dialysis imposed to reduce phosphorus intake, which likely contributes to development of vegetarian diet behaviors. Vegetarian diets are often lower in protein content, in contradiction to the recommendation that a high protein diet is followed by patients undergoing dialysis. The purpose of the study was to investigate the effects of a vegetarian diet on the nutritional and cardiovascular status of dialysis patients. A study of 21 vegetarian dialysis patients and 42 age- and sex-matched non-vegetarian dialysis patients selected as controls was conducted in the Kaohsiung Veterans General Hospital. Brachial-ankle pulse wave velocity and biochemistry data including total homocysteine levels, serum lipid profiles, high-sensitivity C-reactive protein, vitamin D levels, albumin, and normalized protein catabolic rate were measured. Compared with the non-vegetarian control group, vegetarian subjects had lower body weight, body mass index, serum phosphate, blood urea nitrogen, serum creatinine, vitamin D, uric acid, albumin, and normalized protein catabolic rate (p < 0.05). The vegetarian group showed higher brachial-ankle pulse wave velocity than the non-vegetarian group (1926.95 ± 456.45 and 1684.82 ± 309.55 cm/sec, respectively, p < 0.05). After adjustment for age, albumin, pre-dialysis systolic blood pressure, and duration of dialysis, vegetarian diet remained an independent risk factor for brachial-ankle pulse wave velocity. The present study revealed that patients on dialysis who follow vegetarian diets may experience subclinical protein malnutrition and vitamin D deficiency that could offset the beneficial cardiovascular effects of vegetarianism.

Potential Role of Vegetarianism on Nutritional and Cardiovascular Status in Taiwanese Dialysis Patients: A Case-Control Study

PubMed Central

Chen, Mei-Yin; Huang, Chien-Wei; Chen, Nai-Ching; Wu, Chien-Hsing; Hsu, Chih-Yang; Chou, Kang-Ju; Lee, Po-Tsang; Fang, Hua-Chang; Chen, Chien-Liang

2016-01-01

Background & Objectives Cardiovascular disease remains the most common cause of death for patients on chronic dialysis. End stage renal disease patients undergoing dialysis imposed to reduce phosphorus intake, which likely contributes to development of vegetarian diet behaviors. Vegetarian diets are often lower in protein content, in contradiction to the recommendation that a high protein diet is followed by patients undergoing dialysis. The purpose of the study was to investigate the effects of a vegetarian diet on the nutritional and cardiovascular status of dialysis patients. Design, Setting, Participants, Measurements A study of 21 vegetarian dialysis patients and 42 age- and sex-matched non-vegetarian dialysis patients selected as controls was conducted in the Kaohsiung Veterans General Hospital. Brachial-ankle pulse wave velocity and biochemistry data including total homocysteine levels, serum lipid profiles, high-sensitivity C-reactive protein, vitamin D levels, albumin, and normalized protein catabolic rate were measured. Results Compared with the non-vegetarian control group, vegetarian subjects had lower body weight, body mass index, serum phosphate, blood urea nitrogen, serum creatinine, vitamin D, uric acid, albumin, and normalized protein catabolic rate (p < 0.05). The vegetarian group showed higher brachial-ankle pulse wave velocity than the non-vegetarian group (1926.95 ± 456.45 and 1684.82 ± 309.55 cm/sec, respectively, p < 0.05). After adjustment for age, albumin, pre-dialysis systolic blood pressure, and duration of dialysis, vegetarian diet remained an independent risk factor for brachial-ankle pulse wave velocity. Conclusions The present study revealed that patients on dialysis who follow vegetarian diets may experience subclinical protein malnutrition and vitamin D deficiency that could offset the beneficial cardiovascular effects of vegetarianism. PMID:27295214

A novel role of KIF3b in the seminoma cell cycle

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

Shen, Hao-Qing; Xiao, Yu-Xi; She, Zhen-Yu

KIF3b is a protein of the kinesin-2 family which plays an important role in intraflagellar transport. Testis cancer is a common cancer among young men. Its diagnostic rate is increasing and over half of the cases are seminomas. Many aspects of the mechanism and gene expression background of this cancer remain unclear. Using western-blotting and semi-quantitative PCR we found high protein levels of KIF3b enrichment in seminoma tissue despite the mRNA levels remaining equivalent to that of normal testicular tissues. The distribution of KIF3b was mainly in cells with division potential. Wound-healing assays and cell counting kit assays showed thatmore » the knockdown of KIF3b significantly suppressed cell migration ability, viability and number in HeLa cells. Immunofluorescence images during the cell cycle revealed that KIF3b tended to gather at the spindles and was enriched at the central spindle. This indicated that KIF3b may also have direct impacts upon spindle formation and cytokinesis. By counting the numbers of nuclei, spindles and cells, we found that the rates of multipolar division and multi-nucleation were raised in KIF3b-knockdown cells. In this way we demonstrate that KIF3b functions importantly in mitosis and may be essential to seminoma cell division and proliferation as well as being necessary for normal cell division. - Highlights: • A significant upregulation of KIF3b is detected in seminoma. • Knockdown of KIF3b impacts on cell proliferation and migration. • KIF3b may have direct impacts upon spindle formation and cytokinesis.« less

Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease.

PubMed

Kalmar, Bernadett; Innes, Amy; Wanisch, Klaus; Kolaszynska, Alicia Koyen; Pandraud, Amelie; Kelly, Gavin; Abramov, Andrey Y; Reilly, Mary M; Schiavo, Giampietro; Greensmith, Linda

2017-09-01

Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. We found significantly slower retrograde transport of mitochondria in Ser135Phe, Pro39Leu and Arg140Gly mutant Hsp27 expressing motor neurons than in wild type Hsp27 neurons, although anterograde movement velocities remained normal. Retrograde transport of other important cargoes, such as the p75 neurotrophic factor receptor was minimally altered in mutant Hsp27 neurons, implicating that axonal transport deficits primarily affect mitochondria and the axonal transport machinery itself is less affected. Investigation of mitochondrial function revealed a decrease in mitochondrial membrane potential in mutant Hsp27 expressing motor axons, as well as a reduction in mitochondrial complex 1 activity, increased vulnerability of mitochondria to mitochondrial stressors, leading to elevated superoxide release and reduced mitochondrial glutathione (GSH) levels, although cytosolic GSH remained normal. This mitochondrial redox imbalance in mutant Hsp27 motor neurons is likely to cause low level of oxidative stress, which in turn will contribute to, and indeed may be the underlying cause of the deficits in mitochondrial axonal transport. Together, these findings suggest that the mitochondrial abnormalities in mutant Hsp27-induced neuropathies may be a primary cause of pathology, leading to further deficits in the mitochondrial axonal transport and onset of disease. © The Author 2017. Published by Oxford University Press.

Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease

PubMed Central

Innes, Amy; Wanisch, Klaus; Kolaszynska, Alicia Koyen; Pandraud, Amelie; Kelly, Gavin; Abramov, Andrey Y.; Reilly, Mary M.; Schiavo, Giampietro; Greensmith, Linda

2017-01-01

Abstract Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. We found significantly slower retrograde transport of mitochondria in Ser135Phe, Pro39Leu and Arg140Gly mutant Hsp27 expressing motor neurons than in wild type Hsp27 neurons, although anterograde movement velocities remained normal. Retrograde transport of other important cargoes, such as the p75 neurotrophic factor receptor was minimally altered in mutant Hsp27 neurons, implicating that axonal transport deficits primarily affect mitochondria and the axonal transport machinery itself is less affected. Investigation of mitochondrial function revealed a decrease in mitochondrial membrane potential in mutant Hsp27 expressing motor axons, as well as a reduction in mitochondrial complex 1 activity, increased vulnerability of mitochondria to mitochondrial stressors, leading to elevated superoxide release and reduced mitochondrial glutathione (GSH) levels, although cytosolic GSH remained normal. This mitochondrial redox imbalance in mutant Hsp27 motor neurons is likely to cause low level of oxidative stress, which in turn will contribute to, and indeed may be the underlying cause of the deficits in mitochondrial axonal transport. Together, these findings suggest that the mitochondrial abnormalities in mutant Hsp27-induced neuropathies may be a primary cause of pathology, leading to further deficits in the mitochondrial axonal transport and onset of disease. PMID:28595321

Morphine-induced kinetic alterations of choline acetyltransferase of the rat caudate nucleus

PubMed Central

Datta, K.; Wajda, I. J.

1972-01-01

1. In order to explain the decrease of choline acetyltransferase (2.3.1.6.) activity observed in the caudate nucleus of morphine-treated rats, partially purified preparations of the enzyme were used in kinetic studies, with choline as substrate. 2. The apparent Michaelis constant for the enzyme obtained from normal rats was found to be 0·9 mM choline; this value doubled when the animals were killed one hour after a single injection of morphine (30 mg/kg). When the rats were injected daily for 4 or 15 days, and killed one hour after the last injection, the apparent Km value was 2·1 mM in each case. Prolonged daily treatment with morphine, followed by 48 h withdrawal, or by administration of 4 mg/kg of naloxone (given half an hour after the last injection of morphine) resulted in apparent Km values of 1·3-1·5 mM of choline, suggesting a gradual return to the lower, normal substrate requirement. Vmax changes were insignificant. 3. The effect of morphine added in vitro to different enzyme preparations was also studied. The Km values of 0·9 mM, in the enzyme isolated from normal rats, increased to 2·0 after incubation in vitro with 12·5 mM morphine. Similar increases were found in enzymes obtained from rats 48 h after the withdrawal of morphine or from rats injected with naloxone after prolonged morphine treatment. The high apparent Km values, found in enzyme obtained from animals killed one hour after the last dose of morphine, did not change upon incubation with 12·5 mM morphine. A similar pattern of Km changes was noticed after incubation with 25 mM acetylcholine. 4. An increase of 32% in acetylcholine (ACh) level was found in the caudate nucleus one hour after subcutaneous injection of 30 mg/kg of morphine. Return to normal values was observed when morphine was administered daily. After two to three weeks of daily treatment and subsequent withdrawal from morphine for 48 h, the levels of ACh were normal. If the daily treated rats were given naloxone within half an hour of the last injection of morphine, and killed 30 min later, the levels of ACh remained normal. 5. Fifty per cent inhibition of enzyme activity was observed upon in vitro incubation with 75 mM acetylcholine, or with 25 mM morphine. The same degree of inhibition was noticed when the enzyme was obtained from normal or from morphine-treated rats. PMID:5041452

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

PubMed Central

WENISCH, C; WENISCH, H; PARSCHALK, B; VANIJANONTA, S; BURGMANN, H; EXNER, M; ZEDWITZ-LIEBENSTEIN, K; THALHAMMER, F; GEORGOPOULOS, A; GRANINGER, W; LOOAREESUWAN, S

1996-01-01

Serum sCD14, tumour necrosis factor-alpha (TNF-α), IL-6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram-negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n = 16) had higher levels than patients without renal failure (n = 29) (8116+1440 μg/lversus 9453+1017 μg/lP<0.05) and both had higher levels than patients with septicaemia (6155+1635μg/l) and normal subjects (2776+747 μg/l). A significant correlation between sCD14 and IL-6 (r = 0.756) and TNF (r = 0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria. PMID:8697639

Dynamic changes in the hypothalamic-pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study.

PubMed

Wang, Limin; Wang, Qian; Li, Guimei; Liu, Wendong

2015-09-01

The objective of this study was to investigate changes in the hypothalamic-pituitary-adrenal (HPA) axis after recombinant human growth hormone (rhGH) therapy. Subjects included children with growth hormone deficiency (GHD). We conducted a multicenter, retrospective study that assessed 72 GHD patients treated with rhGH during 6 months. Patients were classified into two groups: isolated GHD (IGHD; n=20) and multiple pituitary hormone deficiencies (MPHD; n=52). The HPA axis and other hormones were evaluated at baseline and every 3 months. In the MPHD group, 32 patients had adrenocorticotrophic hormone deficiency and received hydrocortisone before rhGH therapy. In the other 20/52 MPHD patients, the cortisol (COR) level was significantly reduced after rhGH therapy. Moreover, 10 patients showed low COR levels. In the IGHD group, COR levels also decreased, but remained within the normal range. During rhGH therapy, COR levels were reduced, particularly in patients with MPHD. HPA axis should be monitored during rhGH therapy.

pH and salivary sodium bicarbonate during the administration protocol for methotrexate in children with leukemia.

PubMed

Rojas de Morales, Thais; Navas, Rita; Viera, Ninoska; Alvarez, Carmen Julia; Chaparro, Neira; Griman, Dariana

2007-10-01

To analyze the behavior of pH and sodium bicarbonate (NAHCO3) in the saliva of patients with leukemia during the administration protocol for Methotrexate (Mtx). A controlled clinical essay was carried out on 23 patients between 4 and 18 years of age with high-risk Acute Lymphoblastic Leukemia. Sampling was carried out at To: basal condition; T1: 12 hours after intravenous administration of sodium bicarbonate, before administering Mtx and T2: 3 hours after administering Mtx, the time of maximum concentration. Chiron-Diagnostic 378 equipment was used to determine pH and sodium bicarbonate. The data was interpreted using Analysis of Variance at the 5% significance level. The highest values of sodium bicarbonate were observed at T2, with salivary pH levels remaining within neutrality ranges, diminishing slightly in T1. CONCLUSION. In this study, the dose of sodium bicarbonate considered in the administration protocol of 3 g /m2 Mtx, kept sodium bicarbonate levels in saliva at normal levels and pH neutral.

The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.

PubMed

Trabado, Séverine; Al-Salameh, Abdallah; Croixmarie, Vincent; Masson, Perrine; Corruble, Emmanuelle; Fève, Bruno; Colle, Romain; Ripoll, Laurent; Walther, Bernard; Boursier-Neyret, Claire; Werner, Erwan; Becquemont, Laurent; Chanson, Philippe

2017-01-01

Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later

PubMed Central

Fagan, Anne M.; Grant, Elizabeth A.; Hassenstab, Jason; Moulder, Krista L.; Maue Dreyfus, Denise; Sutphen, Courtney L.; Benzinger, Tammie L.S.; Mintun, Mark A.; Holtzman, David M.; Morris, John C.

2013-01-01

Objectives: We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years. Methods: Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. “Expanded” models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared. Results: Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p > 0.074), nor did we find differences between the expanded biomarker models (p > 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p < 0.005). Conclusions: Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms. PMID:23576620

A novel method for quantifying the amount of trabecular meshwork pigment in glaucomatous and nonglaucomatous eyes.

PubMed

Kinori, Michael; Hostovsky, Avner; Skaat, Alon; Schwartsman, Jonathan; Melamed, Shlomo

2014-01-01

To assess the use of a computerized program for evaluating the amount of trabecular meshwork (TM) pigmentation in normal (control), primary open-angle glaucoma (POAG), and pseudoexfoliation glaucoma/pigmentary dispersion glaucoma (PXFG/PDG) patients. All included patients were from the Goldschleger Eye Institute glaucoma clinic. After signing an informed consent, each patient's anterior chamber angle was photographed using a single photo-slit under the same conditions. Only one eye per patient was photographed. The superior TM and the inferior TM were documented. Then, the degree of "blackness" (representing melanin pigment) was assessed using the ImageJ program. Of the 43 eyes photographed, 8 were excluded because of low-quality images. Of the remaining 35 patients, 14 were normal, 10 had POAG, and 11 had PXFG/PDG. The amount of pigment was the same in the control and the POAG patients whether the inferior TM (P=0.24), superior TM (P=0.58), or the sum inferior TM+superior TM (P=0.85) was measured. The pigment level was significantly higher in the PXFG/PDG group than in the control group (inferior TM, P<0.01; superior TM, P=0.047; sum, P<0.01). The difference between the inferior and the superior TM pigment levels was found to be statistically insignificant in all the groups (normal, P=0.86; POAG, P=0.10; PXFG/PDG, P=0.22). The use of ImageJ software might play a role in the quantification of pigment evaluation of the TM.

Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells.

PubMed

França, L R; Leal, M C; Sasso-Cerri, E; Vasconcelos, A; Debeljuk, L; Russell, L D

2000-11-01

Cimetidine (Tagamet) is a potent histaminic H2-receptor antagonist, extensively prescribed for ulcers and now available without prescription. Cimetidine is a known testicular toxicant, but its mechanism of action remains uncertain. Rats were treated i.p. with cimetidine either at 50 mg/kg or 250 mg/kg body weight for 59 days. Accessory sex organ weights, but not testis weight, were significantly reduced in the high dose treated groups. FSH levels were significantly elevated in both treated groups, but testosterone levels were unchanged. A high degree of variability characterized testis histology, with most tubules appearing normal and some tubules (15-17%) partially lacking or devoid of germ cells. Morphometry showed that although seminiferous tubule volume was not significantly changed, the volume of peritubular tissue was reduced in the high dose group. There was extensive duplication of the basal lamina, lamina densa in both apparently normal spermatogenic tubules and severely damaged tubules. Apoptotic peritubular myoid cells were also found. TUNEL labeling confirmed extensive apoptotic cell death in peritubular cells, but revealed apoptosis of vascular smooth muscle. Given that 1) peritubular myoid cell apoptosis occurs in apparently normal tubules, that 2) basal lamina disorders are found, and that 3) peritubular cells are lost from the testis, it is suggested that the primary event in cimetidine-related damage is targeted to testicular smooth muscle cells. This is the first in vivo-administered toxicant to be described that targets myoid cells, resulting in abnormal spermatogenesis.

Are sporadic fidgety movements as clinically relevant as is their absence?

PubMed

Einspieler, Christa; Yang, Hong; Bartl-Pokorny, Katrin D; Chi, Xia; Zang, Fei-Fei; Marschik, Peter B; Guzzetta, Andrea; Ferrari, Fabrizio; Bos, Arend F; Cioni, Giovanni

2015-04-01

Infants with normal fidgety movements at 3 to 5 months after term are very likely to show neurologically normal development, while the absence of fidgety movements is an early marker for an adverse neurological outcome, mainly cerebral palsy (CP). The clinical significance of so-called sporadic fidgety movements (i.e., fidgety movements occur isolated in a few body parts and are of 1- to 3-second-duration) is not yet known. Our objective was to determine whether infants who had developed CP and had sporadic fidgety movements have a better outcome than infants who did not have fidgety movements. Longitudinal study. Retrospective analysis of prospectively collected data. 61 infants who developed CP (46 male, 15 female; 29 infants born preterm; videoed for the assessment of movements and postures at 9 to 16 weeks post-term age). The Gross Motor Function Classification System (GMFCS) was applied at 3 to 5 years of age. There was no difference between children diagnosed with CP who had sporadic fidgety movements at 9 to 16 weeks post-term age (n = 9) and those who never developed fidgety movements (n = 50) with regard to their functional mobility and activity limitation at 3 to 5 years of age. One infant had normal FMs and developed unilateral CP, GMFCS Level I; the remaining infant had abnormal FMs and developed bilateral CP, GMFCS Level II. There is no evidence that the occurrence of occasional isolated fidgety bursts indicates a milder type of CP. Copyright © 2015. Published by Elsevier Ireland Ltd.

Destruction of newly released red blood cells in space flight

NASA Technical Reports Server (NTRS)

Alfrey, C. P.; Udden, M. M.; Huntoon, C. L.; Driscoll, T.

1996-01-01

Space flight results in a rapid change in total blood volume, plasma volume, and red blood cell mass because the space to contain blood is decreased. The plasma volume and total blood volume decreases during the first hours in space and remain at a decreased level for the remainder of the flight. During the first several hours following return to earth, plasma volume and total blood volume increase to preflight levels. During the first few days in space recently produced red blood cells disappear from the blood resulting in a decrease in red blood cell mass of 10-15%. Red cells 12 d old or older survive normally and production of new cells continues at near preflight levels. After the first few days in space, the red cell mass is stable at the decreased level. Following return to earth the hemoglobin and red blood cell mass concentrations decrease reflecting the increase in plasma volume. The erythropoietin levels increase responding to "postflight anemia"; red cell production increases, and the red cell mass is restored to preflight levels after several weeks.

Different underlying pain mechanisms despite identical pain characteristics: a case report of a patient with spinal cord injury.

PubMed

Westermann, Andrea; Krumova, Elena K; Pennekamp, Werner; Horch, Christoph; Baron, Ralf; Maier, Christoph

2012-07-01

Pain following spinal cord injury has been classified as nociceptive (musculoskeletal, visceral) or neuropathic (above, at, below level). There is no clear relation between the etiology and reported symptoms. Thus, due to different underlying mechanisms, the treatment is often ineffective. We report on a patient with spinal cord injury with neurological level of injury at T8 suffering from bilateral burning and prickling pain in the T9-11 dermatomes bilaterally (at-level pain), as well as diffusely in both legs from below the torso (below-level pain), accompanied by musculoskeletal low back pain. Bilateral comparison of quantitative sensory testing (QST) and skin biopsy revealed completely different findings in the dermatome T9 despite identical at-level pain characteristics. On the right side, QST revealed a normal sensory profile; the intraepidermal nerve fiber density (IENFD) was reduced, but not as severe as the contralateral side. On the left side there was a severe sensory loss with a stronger reduction of the IENDF, similar to the areas below the neurological level. These findings were significantly related to the treatment results. Pregabalin induced unilateral pain relief only in the area with remaining sensory function, whereas the left-sided at-level pain was unchanged. Thus, 2 different underlying mechanisms leading to bilaterally neuropathic pain with identical symptoms and with different treatment success were demonstrated in a single patient. The at-level pain in areas with remaining sensory function despite IENFD reduction could be relieved by pregabalin. Thus, in an individual case, QST may be helpful to better understand pain-generating mechanisms and to initiate successful treatment. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Neurotrophin levels and behaviour in BALB/c mice: impact of intermittent exposure to individual housing and wheel running.

PubMed

Zhu, Shun-Wei; Pham, Therese M; Aberg, Elin; Brené, Stefan; Winblad, Bengt; Mohammed, Abdul H; Baumans, Vera

2006-02-15

This study assessed the effects of intermittent individual housing on behaviour and brain neurotrophins, and whether physical exercise could influence alternate individual-housing-induced effects. Five-week-old BALB/c mice were either housed in enhanced social (E) or standard social (S) housing conditions for 2 weeks. Thereafter they were divided into six groups and for 6 weeks remained in the following experimental conditions: Control groups remained in their respective housing conditions (E-control, S-control); enhanced individual (E-individual) and standard individual (S-individual) groups were exposed every other day to individual cages without running-wheels; enhanced running-wheel (E-wheel) and standard running-wheel (S-wheel) groups were put on alternate days in individual running-wheel cages. Animals were assessed for activity in an automated individual cage system (LABORAS) and brain neurotrophins analysed. Intermittent individual housing increased behavioural activity and reduced nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in frontal cortex; while it increased BDNF level in the amygdala and BDNF protein and mRNA in hippocampus. Besides normalizing motor activity and regulating BDNF and NGF levels in hippocampus, amygdala and cerebellum, physical exercise did not attenuate reduction of cortical NGF and BDNF induced by intermittent individual housing. This study demonstrates that alternate individual housing has significant impact on behaviour and brain neurotrophin levels in mice, which can be partially altered by voluntary physical exercise. Our results also suggest that some changes in neurotrophin levels induced by intermittent individual housing are not similar to those caused by continuous individual housing.

Histone methyltransferase G9a modulates hepatic insulin signaling via regulating HMGA1.

PubMed

Xue, Weili; Huang, Jin; Chen, Hong; Zhang, Yu; Zhu, Xiuqin; Li, Jianshuang; Zhang, Wenquan; Yuan, Yangmian; Wang, Yan; Zheng, Ling; Huang, Kun

2018-02-01

Hepatic insulin sensitivity is critical for glucose homeostasis, and insulin resistance is a fundamental syndrome found in various metabolic disorders, including obesity and type 2 diabetes. Despite considerable studies on the mechanisms of hepatic insulin resistance, the link between epigenetic regulation and the development of insulin resistance remains elusive. Here, we reported that G9a/EHMT2, a histone methyltransferase, was markedly decreased in the liver of db/db mice and high-fat diet (HFD)-fed mice. In cultured hepatic cells, G9a knockdown resulted in downregulation of insulin receptor, p-AKT and p-GSK3β; while upon upregulation, G9a prevented the palmitic acid- or glucosamine-induced insulin resistance by preserving the normal level of insulin receptor and integrity of insulin signaling. Further mechanistic study suggested that G9a regulated the expression level of high mobility group AT-hook 1 (HMGA1), a key regulator responsible for the transcription of insulin receptor (INSR) gene. Overexpression of HMGA1 normalized the impaired insulin signaling in G9a knockdown hepatic cells. Importantly, in db/db mice, restoring the expression level of G9a not only upregulated HMGA1 level and improved the impaired hepatic insulin signaling, but also alleviated hyperglycemia and hyperinsulinemia. Together, our results revealed a novel role for G9a in modulating insulin signaling, at least in part, depending on its regulatory function on HMGA1. Copyright © 2017 Elsevier B.V. All rights reserved.

Rate of disappearance of gas bubble trauma signs in juvenile salmonids

USGS Publications Warehouse

Hans, K.M.; Mesa, M.G.; Maule, A.G.

1999-01-01

To assess the rate of disappearance of gas bubble trauma (GBT) signs in juvenile salmonids, we exposed spring chinook salmon Oncorhynchus tshawytscha and steelhead O. mykiss to water containing high levels of dissolved gas supersaturation (DGS) for a time period sufficient to induce signs of GBT, reduced the DGS to minimal levels, and then sampled fish through time to document changes in severity of GBT. Because of the tendency of GBT signs to dissipate at different rates, we conducted trials focusing on emboli (bubbles) in the gill filaments and lateral line and separate trials that focused on bubbles in the external surfaces (fins, eyes, and opercula). Bubbles in gill filaments dissipated almost completely within 2 h after transfer of fish to water of nearly normal DGS (104%), whereas bubbles in the lateral line dissipated to negligible levels within 5 h. Bubbles on external surfaces were more persistent through time than they were in gill filaments and the lateral line. Although typically dissipating to low levels within 48 h, external bubbles sometimes remained for 4 d. Assuming a direct relation exists between easily observable signs and direct mortality, our results suggest that fish can recover quickly from the potentially lethal effects of DGS once they move from water with high DGS to water of almost normal gas saturation. These results should be of fundamental importance to fishery managers interpreting the results of monitoring for the severity and prevalence of GBT in juvenile salmonids in the Columbia River system and perhaps elsewhere.

CXCR6 promotes tumor cell proliferation and metastasis in osteosarcoma through the Akt pathway.

PubMed

Ma, Yunsheng; Xu, Xin; Luo, Mei

2017-01-01

Chemokine (C-X-C motif) receptor 6 (CXCR6) is up-regulated in many malignancies, indicating that CXCR6 plays an important role in tumor progression. However, the expression and function of CXCR6 in osteosarcoma (OS) remains unclear. This study aimed to explore the expression levels and function of CXCR6 in OS tissues and osteosarcoma cell lines MG-63, HOS and U2OS. The protein expression levels of CXCR6 in OS patient tissues and three osteosarcoma cell lines MG-63, HOS and U2OS were assessed. CXCR6-overexpression MG-63 cell lines were established and then the proliferation, invasion and the epithelial-mesenchymal transition (EMT) in those cells were assessed. CXCR6 mRNA levels in OS tissues were significantly higher than those in normal bone tissues. Consistently, both of the mRNA and protein levels of CXCR6 in OS cell lines MG-63, HOS and U2OS were higher than those in normal bone cells hFOB1.19. CXCR6 overexpression not only promoted cell proliferation, invasion and EMT, but also enhanced the phosphorylation of Akt in MG-63 cells. After inhibition of Akt-phosphorylation by Akt inhibitor, LY2940023, CXCR6-induced cell proliferation and invasion were dramatically attenuated. In conclusion, the present study demonstrated that CXCR6 enhances OS cell proliferation and invasion through the Akt pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypothalamic orexin prevents hepatic insulin resistance via daily bidirectional regulation of autonomic nervous system in mice.

PubMed

Tsuneki, Hiroshi; Tokai, Emi; Nakamura, Yuya; Takahashi, Keisuke; Fujita, Mikio; Asaoka, Takehiro; Kon, Kanta; Anzawa, Yuuki; Wada, Tsutomu; Takasaki, Ichiro; Kimura, Kumi; Inoue, Hiroshi; Yanagisawa, Masashi; Sakurai, Takeshi; Sasaoka, Toshiyasu

2015-02-01

Circadian rhythm is crucial for preventing hepatic insulin resistance, although the mechanism remains uncovered. Here we report that the wake-active hypothalamic orexin system plays a key role in this regulation. Wild-type mice showed that a daily rhythm in blood glucose levels peaked at the awake period; however, the glucose rhythm disappeared in orexin knockout mice despite normal feeding rhythm. Central administration of orexin A during nighttime awake period acutely elevated blood glucose levels but subsequently lowered daytime glucose levels in normal and diabetic db/db mice. The glucose-elevating and -lowering effects of orexin A were suppressed by adrenergic antagonists and hepatic parasympathectomy, respectively. Moreover, the expression levels of hepatic gluconeogenic genes, including Pepck, were increased and decreased by orexin A at nanomolar and femtomolar doses, respectively. These results indicate that orexin can bidirectionally regulate hepatic gluconeogenesis via control of autonomic balance, leading to generation of the daily blood glucose oscillation. Furthermore, during aging, orexin deficiency enhanced endoplasmic reticulum (ER) stress in the liver and caused impairment of hepatic insulin signaling and abnormal gluconeogenic activity in pyruvate tolerance test. Collectively, the daily glucose rhythm under control of orexin appears to be important for maintaining ER homeostasis, thereby preventing insulin resistance in the liver. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

[Effect of qinghuobaiduyin on the expression of high mobility group box chromosomal protein 1 in macrophage].

PubMed

Li, Ping; Xu, Dan; Luo, Chengqun

2010-07-01

To observe the expression of high mobility group box chromosomal protein 1(HMGB1) in RAW264.7 macrophages after interfering with burning serum and qinghuobaidu-yin (QHBDY), and to find out the endogenous protection mechanism of QHBDY resisting inflammation reaction. RT-PCR was used to detect the expression of HMGB1 in RAW264.7 macrophages after interfering RAW264.7 macrophages with normal SD rat serum, burning SD rat serum, and QHBDY feeding SD rat serum. Small quantity of HMGB1 mRNA was expressed in RAW264.7. The expression of HMGB1 mRNA fluctuated around the standard level after interfering with normal serum of SD rats. The expression of HMGB1 mRNA rose at 3 h, and then decreased to the standard level; at 18 h, it rose rapidly; at 36 h, it reached the peak; and at 48 h, it remained at the high level after interfering with burning serum. The expression of HMGB1 mRNA increased at 3 h, and then decreased to the standard level. At 24 h, it started to rise after interfering with herb serum, and was lower than that of; the burning serum group (P<0.05). Burning serum can increase the expression of HMGB1 mRNA in RAW264.7. QHBDY can decrease the high expression of HMGB1 mRNA in RAW264.7 caused by burning serum.

Restoration of blood 2,3-diphosphoglycerate levels in multi-transfused patients: effect of organic and inorganic phosphate.

PubMed

Iapichino, G; Radrizzani, D; Solca, M; Franzosi, M G; Pallavicini, F B; Spina, G; Scherini, A

1984-01-01

Blood stored in acid-citrate-dextrose (ACD) shows a progressive decrease in 2,3-diphosphoglycerate (DPG) content. Since the decrease in DPG increases hemoglobin oxygen affinity, which in turn may reduce tissue and venous PO2 and peripheral oxygen delivery, many efforts have been made to preserve or restore DPG levels in stored blood. An in vivo rejuvenating technique, employing fructose-1,6-diphosphate (FDP) at a mean dosage of 1 mmol kg-1 day-1 of phosphate, to increase the DPG circulating level in multi-transfused patients is proposed. Eighteen patients, who received at least one-third of their estimated blood volume (3990 +/- 480 (SEM) ml of ACD stored blood) in blood transfusion, were treated: nine with inorganic phosphate, and nine with FDP. Basal DPG was very low in both groups: 12.61 +/- 1.34 (SEM) and 10.42 +/- 0.98 (SEM) mumol g-1, respectively (normal value is 14.5 mumol g-1, at pH 7.40). However, DPG values increased significantly and promptly in patients receiving FDP, whereas in cases of inorganic phosphate administration, it was not significantly raised over the basal value until the third day. Phosphatemia remained normal and constant with FDP, but it rose significantly on the third day of treatment with inorganic phosphate. FDP appears to consistently and rapidly increase DPG levels after transfusion with blood stored in ACD, and to be particularly safe.

Clinical case report: a rare cause of acute kidney failure - tissue is the issue.

PubMed

Heggermont, Ward A; Verhoef, Gregor; Evenepoel, Pieter; Sprangers, Ben; Lerut, Evelyn; Tousseyn, Thomas; Claes, Kathleen

2017-06-01

A patient was admitted to the medical emergency department by his family physician. His complaints were weakness and fatigue for more than one week. Four days before admission, he went to his general practitioner for these complaints and also for painful elbows. His physician prescribed diclofenac and esomeprazole. Upon presentation, he had high systolic/diastolic blood pressure (>180/>90 mm Hg, measured repeatedly), and otherwise normal parameters. He had gained 6.5 kg in body weight. Clinical examination was normal, except for very mild bilateral malleolar edema. Routine blood tests showed a strongly elevated serum creatinine, hyperkalemia, and elevated lactate dehydrogenase. Haptoglobin levels were normal. Urinalysis showed a normal sediment, urine and blood cultures remained sterile. Ophthalmoscopy was completely normal, as was a routine chest X-ray. Renal ultrasound demonstrated kidneys with a diameter of 13 cm. Due to uncontrollable hypertension, our patient was hospitalized at the intensive care department where intravenous nifedipine was started, with good instantaneous control of blood pressure. Because of increasing potassium levels acute hemodialysis was started within 24 h after admission. Differential diagnosis consisted of diclofenac- or esomeprazole-induced interstitial nephritis or rapidly progressive glomerulonephritis. A renal biopsy was performed within 72 h after admission. The kidney biopsy showed an overwhelming inflammatory cell infiltrate consisting of a monoclonal lymphocytic cell population. However, the numerous mitotic figures, polyploidy, and prominent nucleoli present, were indicative of a lymphoma. Additional stainings confirmed a non-Hodgkin diffuse large-cell B-cell lymphoma. Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, and prednisolone) was initiated with very good clinical and biochemical response, yet only mild recovery of kidney function. Occasionally the kidney is involved as an extranodal non-Hodgkin lymphoma (NHL) localization. However, a primary presentation of acute kidney failure due to lymphoma localization is extremely rare. Our case demonstrates that early renal biopsy is indispensable for fast and adequate diagnosis and treatment.

A re-evaluation of the effects of X-linked immunodeficiency (xid) mutation on B cell differentiation and function in the mouse.

PubMed

Klaus, G G; Holman, M; Johnson-Léger, C; Elgueta-Karstegl, C; Atkins, C

1997-11-01

CBA/N (xid) mice have a point mutation in Bruton's tyrosine kinase (btk), which results in their failure to respond to T-independent type 2 (TI-2) antigens, and to several B cell mitogens [most notably anti-immunoglobulin (Ig)] in vitro. They have reduced numbers of peripheral (B2) B cells, which are regarded as being phenotypically and functionally immature. We show here that adult CBA/N mice in fact have two distinct B cell populations: some 60% of the cells are CD23+ HSAlo sIgDhi and hence resemble recirculating, follicular (RF) B cells from normal mice, except that they are sIgMhi. The remaining 40% of xid B cells are CD23- HSAhi sIgD-/lo and resemble immature transitional (TR) B cells. TR B cells from xid mice do not synthesize DNA when cultured with lipopolysaccharide (LPS), whereas those from normal mice do so. Only the RF cells from either xid or normal mice proliferate in response to ligation of CD40. In neonatal normal mice the emergence of mitogen responsiveness followed the chronological sequence LPS-->anti-CD40-->anti-Ig approximately anti-CD38. The same developmental sequence was seen with B cells from xid mice (for LPS and anti-CD40), but it occurred at a significantly slower tempo and this correlated with the later appearance of RF-type cells. TR xid B cells express very low levels of bcl-2 and we conclude that these cells resemble very immature (bone marrow) B cells, rather than normal transitional cells. We, therefore, propose that the xid mutation imposes a multistage brake on B cell differentiation in the mouse. The available data suggest that btk is required for the positive selection of B cells throughout their differentiation in the periphery. This in turn implies that low level signaling via surface Ig is needed throughout this process in order for peripheral B cells to become functionally mature.

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data.

PubMed

Li, Xiaohong; Brock, Guy N; Rouchka, Eric C; Cooper, Nigel G F; Wu, Dongfeng; O'Toole, Timothy E; Gill, Ryan S; Eteleeb, Abdallah M; O'Brien, Liz; Rai, Shesh N

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level.

A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data

PubMed Central

Li, Xiaohong; Brock, Guy N.; Rouchka, Eric C.; Cooper, Nigel G. F.; Wu, Dongfeng; O’Toole, Timothy E.; Gill, Ryan S.; Eteleeb, Abdallah M.; O’Brien, Liz

2017-01-01

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level. PMID:28459823

Age-Specific Normal Reference Range for Serum Anti-Müllerian Hormone in Healthy Chinese Han Women: A nationwide Population-Based Study.

PubMed

Du, Xiaofang; Ding, Ting; Zhang, Hanwang; Zhang, Cuilian; Ma, Wenmin; Zhong, Ying; Qu, Wenyu; Zheng, Jie; Liu, Yi; Li, Zhiying; Huang, Kecheng; Deng, Song; Ma, Lanfang; Yang, Jun; Jiang, Jingjing; Yang, Shuhong; Huang, Jia; Wu, Meng; Fang, Li; Lu, Yunping; Luo, Aiyue; Wang, Shixuan

2016-08-01

The increasing use of anti-Müllerian hormone (AMH) in clinic has raised concerns regarding the reliable reference range for this test. However, the reference range for AMH in normal Chinese female population has not been established. Furthermore, relationship between AMH and other clinical markers such as body mass index (BMI) and antral follicle counts (AFCs) and other sex-related hormones have not been examined in normal population-based women. We aimed to determine the age-specific reference range for serum AMH in healthy Chinese women throughout reproductive age to menopause and to estimate relationship between AMH and other clinical markers in healthy women. In this multicenter and nationwide study, advertisements were used to recruit 2055 women, aged 20 to 55 years, from 6 different regions in China; 1590 (77.37%) women met the inclusion criteria for the reference range population. We measured the baseline serum AMH levels using new Beckman Coulter Gen II assay. Serum concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), progesterone (PRG), and AFCs were also determined in the follicular phase. The AMH-Age nomogram and AMH levels of different age-groups and the relationship between AMH and other clinical markers. Serum AMH concentrations declined progressively with age. A quadratic model defined as log (AMH) = (-1.970 + 0.296 × Age - 0.006 × Age(2)) fitted best the decline of AMH with age. The median AMH levels were 6.23, 5.65, 4.55, 3.74, 2.78, and 1.09 ng/mL for the 20 ≤ age < 25, 25 ≤ age < 30, 30 ≤ age < 33, 33 ≤ age < 37, 37 ≤ age < 40, and 40 ≤ age < 55 groups, respectively. The 5th to 95th percentiles of the AMH levels, as the reference range, were 2.06 to 12.66, 1.77 to 13.83, 1.48 to 11.45, 0.87 to 9.76, 0.56 to 9.49, and 0.08 to 5.70 ng/mL for each age-group. The AMH levels were positively correlated with AFCs and T, LH, PRL and PRG levels and negatively correlated with BMI and FSH levels and were not significantly correlated with E2 levels. The relationship between AMH and other variables remain unchanged except for PRL, which was not significantly correlated with AMH levels after controlling for both age and BMI. This study determined the normal reference ranges for serum AMH levels in a large population-based sample of healthy Chinese women. © The Author(s) 2016.

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

PubMed

Sathya, S; Kokilavani, R; Gurusamy, K

2008-10-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level.

Cell-derived microparticles after exercise in individuals with G6PD Viangchan.

PubMed

Chanda, Makamas; Nantakomol, Duangdao; Suksom, Daroonwan; Palasuwan, Attakorn

2015-07-16

Glucose-6-phospate dehydrogenase (G6PD) deficient cells are sensitive to oxidative damage leading to the formation of microparticles (MPs). Therefore, we examined the concentration of MPs and changes in the antioxidant balance after an acute strenuous exercise (SEx) and moderate-intensity exercise (MEx). Eighteen healthy females (18-24 years) with G6PD normal and eighteen age-matched females with G6PD Viangchan (871G>A) were tested by running on a treadmill at their maximal oxygen uptake for SEx and at 75% of their maximal heart rate for MEx. It was found that SEx triggered the release of total microparticles (TTMPs) above baseline levels and remained significantly higher 45 minutes after the exercise in G6PD normal individuals. However, SEx-induced increase in TTMPs was significantly higher in G6PD Viangchan as compared to G6PD normal. In contrast, MEx did not to alter the release of TTMPs in both G6PD normal and Viangchan. Moreover, TTMPs concentrations were inversely correlated with G6PD activity (r =-0.82, P <  0.05) but positively correlated with MDA concentrations (r = 0.74, P <  0.05). Using cell specific antibodies, we determined that MPs were mainly derived from platelets and erythrocytes. Altogether, the present study indicates that G6PD Viangchan may participate in MEx without higher MPs concentration and oxidative stress compared with G6PD normal.

Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion.

PubMed

Ortega-Sáenz, Patricia; Macías, David; Levitsky, Konstantin L; Rodríguez-Gómez, José A; González-Rodríguez, Patricia; Bonilla-Henao, Victoria; Arias-Mayenco, Ignacio; López-Barneo, José

2016-12-15

Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB). In biotin-deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis. Remarkably, glomus cells from these animals have normal electrical and neurochemical properties. However, they show a marked decrease in the size of quantal dopaminergic secretory events. Inhibitors of the vesicular monoamine transporter 2 (VMAT2) mimic the effect of biotin deficiency. In biotin-deficient animals, VMAT2 protein expression decreases in parallel with biotin depletion in CB cells. These data suggest that dopamine transport and/or storage in small secretory granules in glomus cells depend on biotin. Biotin is a water-soluble vitamin required for the function of carboxylases as well as for the regulation of gene expression. Here, we report that biotin accumulates in unusually large amounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). We show in a biotin-deficient rat model that the vitamin rapidly disappears from the blood and other tissues (including the AM), while remaining at relatively high levels in the CB. We have also observed that, in comparison with other peripheral neural tissues, CB cells contain high levels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Biotin-deficient rats show a syndrome characterized by marked weight loss, metabolic lactic acidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably, CB cells from biotin-deficient animals have normal electrophysiological and neurochemical (ATP levels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the size of quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differential secretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor of the vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (in comparison with VMAT1), and in biotin-deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotin has an essential role in the homeostasis of dopaminergic transmission modulating the transport and/or storage of transmitters within small secretory granules in glomus cells. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Testicular function during puberty and young adulthood in patients with Klinefelter's syndrome with and without spermatozoa in seminal fluid.

PubMed

Rohayem, J; Nieschlag, E; Zitzmann, M; Kliesch, S

2016-11-01

Patients with Klinefelter's syndrome experience progressive testicular degeneration resulting in impaired endocrine function and azoospermia. What proportion of adolescents develop testosterone deficiency during puberty and how many have spermatozoa in their semen is unclear to date. We aimed to investigate testicular function during puberty and young adulthood in patients with Klinefelter's syndrome and to assess testosterone effects in target tissues. The clinical data of 281 patients with non-mosaic Klinefelter's syndrome aged 10-25 years without previous testosterone replacement were reviewed. In late pubertal adolescents, semen analyses were evaluated, and testicular volumes, hormone and haemoglobin (Hb) levels, the number of CAG repeats and final height data were compared to those of 233 age-matched controls with pubertal gynaecomastia. Spontaneous pubertal virilisation to Tanner stages IV-V occurred. Serum T levels ≥10 nmol/L were reached in 62% of patients with Klinefelter's syndrome and in 85% of controls at ages 15-25 (T KFS : 12.2 ± 5.4 vs. T C : 16.6 ± 7.2 nmol/L). LH KFS levels were elevated >10 U/L in 84%, and normal in all controls (LH KFS : 18.6 ± 12.2 vs. LH C : 3.5 ± 1.6 U/L). In nine of 130 (7%) adolescents with Klinefelter's syndrome, spermatozoa (oligozoospermia) were found in semen; all had T levels >7 nmol/L and eight of nine had LH levels ≤18 U/L, while their hormone levels, number of CAG repeats and testicular volumes were not different from those of adolescents with azoospermia. Controls had normal sperm concentrations in 73% (46/63). Semen volumes KFS were normal in 55% vs. 78% in controls; Hb KFS was normal in 89% (Hb C : 97%). Mean final height KFS was 185 ± 8 cm vs. 181 ± 7 cm in controls. Hypergonadotropic hypogonadism develops during early puberty in adolescents with Klinefelter's syndrome and remains compensated in over 60% during ages 15-25, with sufficient testosterone secretion for spontaneous accomplishment of pubertal development. Spermatozoa in semen are rare and associated with T levels >7 nmol/L. Parameters reflecting androgen deficiency in target tissues may help to optimise timing of testosterone substitution, which should preferably not be initiated before fertility status has been clarified. © 2016 American Society of Andrology and European Academy of Andrology.

Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence

PubMed Central

Boileau, Isabelle; McCluskey, Tina; Tong, Junchao; Furukawa, Yoshiaki; Houle, Sylvain; Kish, Stephen J

2016-01-01

We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [11C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [11C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [11C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [11C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication. PMID:26321315

Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence.

PubMed

Boileau, Isabelle; McCluskey, Tina; Tong, Junchao; Furukawa, Yoshiaki; Houle, Sylvain; Kish, Stephen J

2016-03-01

We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [(11)C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [(11)C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [(11)C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [(11)C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication.

Isotretinoin kinetics after 80 to 320 mg oral doses.

PubMed

Colburn, W A; Gibson, D M

1985-04-01

Twelve healthy male subjects received 80, 160, 240, and 320 mg doses of oral isotretinoin as multiples of 40 mg capsules separated by 2-week washout periods in a randomized, crossover design. Blood samples were drawn at specific times over a 72-hour period after dosing. Blood concentrations of isotretinoin as well as its major metabolite, 4-oxo-isotretinoin, were determined by a specific HPLC method. In addition to the normal laboratory battery of tests, serum triglyceride levels were determined before the first dose and again 72 hours after each of the four doses. Mean (+/- SD) maximum concentrations after 80 to 320 mg doses were 366 +/- 159, 820 +/- 474, 1056 +/- 547, and 981 +/- 381 ng/ml, whereas the respective AUC0-infinity values were 3690 +/- 1280, 7030 +/- 4140, 9780 +/- 6080, and 9040 +/- 2900 ng X hr/ml. The observed apparent elimination t1/2 remained approximately the same (14.7 hours) for each dose. The maximum concentration and AUC values for isotretinoin appear to be dose proportional from 80 to 240 mg but plateau at the 320 mg dose level. Therefore, because isotretinoin blood concentrations may not increase with higher doses in the fasting state, single, oral doses in excess of 240 mg should be used with caution. The data also suggest that elevated triglyceride levels are not a simple function of isotretinoin blood concentrations across the entire study population and dose range studied, but that in subjects with triglyceride levels in excess of the normal range triglyceride levels were positively related to isotretinoin blood concentrations.

The secretory pattern and source of immunoreactive prolactin in pregnant African (Loxodonta africana) and Asian (Elephas maximus) elephants.

PubMed

Yamamoto, Yuki; Yamamoto, Tatsuya; Yuto, Natsuki; Hildebrandt, Thomas B; Lueders, Imke; Wibbelt, Gudrun; Shiina, Osamu; Mouri, Yasushi; Sugimura, Keisuke; Sakamoto, Sayuri; Kaewmanee, Saroch; Nagaoka, Kentaro; Watanabe, Gen; Taya, Kazuyoshi

2012-01-01

The objective of the present study was to define the secretion of prolactin (PRL) in pregnant African and Asian elephants. Levels of immunoreactive (ir-) PRL in serum and placental homogenates were measured by a heterologous radioimmunoassay (RIA) based on an ovine and human RIA system, and the localization of ir-PRL in the placenta was detected by immunohistochemistry using anti-human PRL. Circulating ir-PRL clearly showed a biphasic pattern during pregnancy in African and Asian elephants. Serum levels of ir-PRL started to increase from the 4 - 6th month of gestation and reached the first peak level around the 11-14th month. A second peak of circulating ir-PRL levels was observed around the 18-20th month of gestation followed by an abrupt decline after parturition. In contrast, in a case of abortion of an African elephant, the second peak of ir-PRL was not observed, and the levels remained low for about four months until parturition. The weight of the fetus delivered at the 17th month of gestation was 23.5 kg, which was quite small compared with normal fetuses in previous reports. Ir-PRL was detected in placental homogenates, and immunolocalization was observed in trophoblasts in both the African and Asian elephants, indicating that the placenta is the source of ir-PRL during pregnancy in elephants. The present results clearly demonstrated that circulating ir-PRL shows a biphasic pattern during normal pregnancy and that the placenta appears to be an important source of circulating ir-PRL during pregnancy in both African and Asian elephants.

Reduced plasma levels of coagulation factors in relation to prostate cancer.

PubMed

Beecken, Wolf-Dietrich; Bentas, Wassilios; Engels, Knut; Glienke, Wolfgang; Urbschat, Anja; Jonas, Dietger; Binder, Jochen; Scharrer, Inge

2002-10-01

Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Copyright 2002 Wiley-Liss, Inc.

Relative distribution of ketamine and norketamine in skeletal tissues following various periods of decomposition.

PubMed

Watterson, James H; Donohue, Joseph P

2011-09-01

Skeletal tissues (rat) were analyzed for ketamine (KET) and norketamine (NKET) following acute ketamine exposure (75 mg/kg i.p.) to examine the influence of bone type and decomposition period on drug levels. Following euthanasia, drug-free (n = 6) and drug-positive (n = 20) animals decomposed outdoors in rural Ontario for 0, 1, or 2 weeks. Skeletal remains were recovered and ground samples of various bones underwent passive methanolic extraction and analysis by GC-MS after solid-phase extraction. Drug levels, expressed as mass normalized response ratios, were compared across tissue types and decomposition periods. Bone type was a main effect (p < 0.05) for drug level and drug/metabolite level ratio (DMLR) for all decomposition times, except for DMLR after 2 weeks of decomposition. Mean drug level (KET and NKET) and DMLR varied by up to 23-fold, 18-fold, and 5-fold, respectively, between tissue types. Decomposition time was significantly related to DMLR, KET level, and NKET level in 3/7, 4/7, and 1/7 tissue types, respectively. Although substantial sitedependence may exist in measured bone drug levels, ratios of drug and metabolite levels should be investigated for utility in discrimination of drug administration patterns in forensic work.

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles

PubMed Central

Varshosaz, J.; Minaiyan, M.; Forghanian, M.

2014-01-01

The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1), iv solution of sCT (5 μg·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly. PMID:24701588

A rare case of multifocal intramedullary germinoma in cervical spinal cord.

PubMed

Wang, R; Fan, X; Zhang, B

2014-06-01

Case report. We present for the first time a patient with multifocal intramedullary cervical spinal cord germ cell tumors with elevated serum alpha-fetoprotein (AFP). Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. A 19-year-old girl experienced numbness in her right leg 10 months before diagnosis. The numbness gradually became severe and extended up to the thorax. Magnetic resonance imaging (MRI) visualized several intramedullary masses with intensive enhancement and extensive peritumoral edema in the spinal cord at the C3-T1 vertebral body levels. Administration of methylprednisolone caused no treatment effect. The largest mass, which was located at the T1 level inside the normal spinal cord and confirmed by naked eye observation, was completely extracted under a microscope. Postoperative pathological examination demonstrated the so-called 'two-cell pattern,' which is typical of germinoma with placental alkaline phosphatase expression. The serum level of AFP was 64.50 ng ml(-1) (normal range: 0-5 ng ml(-1)). The residual tumor was eliminated through radiation therapy (local 30 Gy) following surgery. Afterward, the patient's neurological deficits were improved but not resolved. Six years after surgery, no recurrence was encountered and the patient remained stable. Radiotherapy is the salvage therapy for spinal cord germinoma. Steroids were of no therapeutic value in the treatment of intramedullary spinal cord germinoma.

Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

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

Ware, R.; Kinney, T.R.; Rosse, W.

1985-11-01

Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms.more » Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a SVI-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.« less

[Effect of cryotherapy over the expression of vascular endothelial growth factor and pigment epithelium-derived factor].

PubMed

Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier

2014-01-01

Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

Genome-wide linkage analysis of human auditory cortical activation suggests distinct loci on chromosomes 2, 3, and 8.

PubMed

Renvall, Hanna; Salmela, Elina; Vihla, Minna; Illman, Mia; Leinonen, Eira; Kere, Juha; Salmelin, Riitta

2012-10-17

Neural processes are explored through macroscopic neuroimaging and microscopic molecular measures, but the two levels remain primarily detached. The identification of direct links between the levels would facilitate use of imaging signals as probes of genetic function and, vice versa, access to molecular correlates of imaging measures. Neuroimaging patterns have been mapped for a few isolated genes, chosen based on their connection with a clinical disorder. Here we propose an approach that allows an unrestricted discovery of the genetic basis of a neuroimaging phenotype in the normal human brain. The essential components are a subject population that is composed of relatives and selection of a neuroimaging phenotype that is reproducible within an individual and similar between relatives but markedly variable across a population. Our present combined magnetoencephalography and genome-wide linkage study in 212 healthy siblings demonstrates that auditory cortical activation strength is highly heritable and, specifically in the right hemisphere, regulated oligogenically with linkages to chromosomes 2q37, 3p12, and 8q24. The identified regions delimit as candidate genes TRAPPC9, operating in neuronal differentiation, and ROBO1, regulating projections of thalamocortical axons. Identification of normal genetic variation underlying neurophysiological phenotypes offers a non-invasive platform for an in-depth, concerted capitalization of molecular and neuroimaging levels in exploring neural function.

In situ monitoring of cytoplasmic precursor and mature microRNA using gold nanoparticle and graphene oxide composite probes.

PubMed

Hong, Min; Sun, Hongxiao; Xu, Lidan; Yue, Qiaoli; Shen, Guodong; Li, Meifang; Tang, Bo; Li, Chen-Zhong

2018-08-27

This study strategically fabricates a nucleic acid functionalized gold nanoparticle and graphene oxide composite probe (AuNP/GO probe) to achieve both the recognition and in situ monitoring of cytoplasmic target precursor microRNAs (pre-miRNAs) and mature microRNAs (miRNAs) in living cells. The pre-miRNA-21 detection with AuNP probes has a good linear range of 0-300 nM and a limit of detection (LOD) of 4.5 nM, whereas the GO probe has a linear relationship with mature miRNA-21 from 0.1 to 10 nM with a LOD of 1.74 nM. This assay was utilized to directly visualize the relative expression levels of pre- and mature forms of miRNA-21 and let-7a. The results suggested that the expression levels of precursor miRNAs remain constant in cancer cells and normal cells. However, the expression levels of mature miRNAs vary widely, demonstrating the "up-regulation" of miRNA-21 and "down-regulation" of let-7a in cancer cells in contrast to that in normal cells. The practicality of this strategy was verified by in situ monitoring changes in cytoplasmic pre-miRNA-21 and mature miRNA-21 in response to small-molecule inhibitors of miRNA-21. Copyright © 2018 Elsevier B.V. All rights reserved.

Postnatal ocular expression of tyrosinase and related proteins: disruption by the pink-eyed unstable (p(un)) mutation.

PubMed

Chiu, E; Lamoreux, M L; Orlow, S J

1993-09-01

Ocular pigmentation in the mouse occurs primarily postnatally as a result of the melanization of neural crest-derived melanocytes. Using immunologic and biochemical techniques, we demonstrate that in normal mice the expression of tyrosinase and the related proteins TRP-1 and TRP-2, rises during the first week of life, remains elevated for a week, and then steadily declines to low levels by adulthood. Sucrose gradient density centrifugation demonstrates that tyrosinase, TRP-1 and TRP-2 are present in high molecular weight forms in the eyes of wild-type mice. The normal time course is disrupted in mice carrying the pink-eyed unstable (p(un)) mutation at the P-locus, a model for tyrosinase-positive albinism in man. Tyrosinase and TRP-2 are present at wild-type levels in the eyes of p(un)/p(un) mice at birth, but, rather than rising, their levels rapidly decline over the first week of life. TRP-1 is almost undetectable, even at birth. High molecular weight complexes could not be detected in eyes of p(un)/p(un) mice. Our results suggest that postnatal ocular melanogenesis in the mouse presents an attractive model for the study of the orderly expression and action of the proteins involved in eumelanin synthesis, and that the p(un) mutation disrupts this temporally controlled process.

Do vegetarians have a normal bone mass?

PubMed

New, Susan A

2004-09-01

Public health strategies targeting the prevention of poor bone health on a population-wide basis are urgently required, with particular emphasis being placed on modifiable factors such as nutrition. The aim of this review was to assess the impact of a vegetarian diet on indices of skeletal integrity to address specifically whether vegetarians have a normal bone mass. Analysis of existing literature, through a combination of observational, clinical and intervention studies were assessed in relation to bone health for the following: lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets, consumption of animal versus vegetable protein, and fruit and vegetable consumption. Mechanisms of action for a dietary "component" effect were examined and other potential dietary differences between vegetarians and non-vegetarians were also explored. Key findings included: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone with high protein consumption (particularly without supporting calcium/alkali intakes) and low protein intake (particularly with respect to vegan diets) being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. The impact of a "vegetarian" diet on bone health is a hugely complex area since: 1) components of the diet (such as calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key lifestyle factors which are important to bone (such as physical activity) may be different; 3) the tools available for assessing consumption of food are relatively weak. However, from data available and given the limitations stipulated above, "vegetarians" do certainly appear to have "normal" bone mass. What remains our challenge is to determine what components of a vegetarian diet are of particular benefit to bone, at what levels and under which mechanisms.

Interleukin-induced increase in Ia expression by normal mouse B cells.

PubMed

Roehm, N W; Leibson, H J; Zlotnik, A; Kappler, J; Marrack, P; Cambier, J C

1984-09-01

The constitutive culture supernatant (SN) of the macrophage tumor line P388D1 (P388 SN) and the concanavalin A (Con A)-induced culture supernatant of the T cell hybridoma FS6-14.13 (FS6 Con A SN) were shown to contain nonspecific factors capable of inducing increased Ia expression by normal resting B cells in a dose-dependent manner. In six consecutive experiments the relative increase in Ia expression induced by P388 SN was 4.9 +/- 0.9, with FS6 Con A SN 10.7 +/- 1.5, and with a combination of both preparations 13.0 +/- 1.7. This increase in Ia expression was observed to occur in virtually all the B cells, reaching maximum levels within 24 h of culture. The interleukin-induced increase in B cell Ia expression occurred in the absence of ancillary signals provided by ligand-receptor Ig cross-linking and despite the fact that virtually all the control B cells, cultured in the absence of factors, remained in G0. These results suggest that functional receptors for at least some interleukins are expressed on normal resting B cells and their effects can be manifest in the absence of additional activating signals. The increased Ia expression induced by the nonspecific factor preparations was shown to be correlated with enhanced antigen-presenting capacity by the B cells to T cell hybridomas. The nature of the interleukins responsible for these effects remains to be definitively determined, however, the activity of FS6 Con A SN was shown to correlate with B cell growth factor activity and increased B cell Ia expression was not observed using interleukin 2 (IL-2) or interferon-gamma, prepared by recombinant DNA technology.

E. coli Multiresistant Meningitis after Transrectal Prostate Biopsy

PubMed Central

Alecsandru, Diana; Gestoso, Israel; Romero, Ana; Martinez, Alfonso; García, Ana; Lobo, Julio; Yagüe, M. Ruiz

2006-01-01

Escherichia coli meningitis is a frequent pathology in children younger than 3 years old, but is an uncommon disease in adults. E. coli infection is the main cause of intrahospital bacteremia as a consequence of the employment of different medical procedures. Our patient, male, 69 years old, presented with fever, progressive difficulty in breathing, and shivers 24 h after transrectal prostate biopsy, with an absence of any other symptoms. He received prophylactic treatment with ciprofloxacin and later empirical treatment with ampicillin and tobramicin. After that, the patient presented with fever, headache, behavioral changes, somnolence, disorientation, a fluctuating level of conscience, cutaneous widespread pallor, and acute urinary retention. On physical exploration, we observed generalized hypoventilation, Glasgow 10, stiffness of the neck, inconclusive Kernig; the remaining neurological exploration was normal. Systematic of blood: leukocytes = 8,510/mm3 (94.5% polymorphonuclear), platelet = 87,000/mm3, pH = 7.51, pCO2 = 28.8 mmHg, pO2 = 61 mmHg, O2 saturation = 93.8%, and remaining values were normal. Chest X- ray, cranial CT scan, urine cultures were normal. Blood culture: E. coli. CSF: glucose <0.4 g/l, total proteins = 3.05 g/l, PMN = 7 cells. Microscopic examination of the CSF: Gram-negative bacilli; CSF's culture: abundant E. coli. The case of acute meningitis by multiresistant E. coli after transrectal prostate biopsy presented demonstrates that antibiotic prevention with ciprofloxacin is not absolutely risk free. Besides the use of antibiotic prevention for multiresistant microorganisms, the urologist and other physicians involved in the procedure must not forget that the rate of major complications of transrectal prostate biopsy is 1%, especially when it is performed in patients who will not benefit from that biopsy. PMID:17619698

A predictive nondestructive model for the covariation of tree height, diameter, and stem volume scaling relationships.

PubMed

Zhang, Zhongrui; Zhong, Quanlin; Niklas, Karl J; Cai, Liang; Yang, Yusheng; Cheng, Dongliang

2016-08-24

Metabolic scaling theory (MST) posits that the scaling exponents among plant height H, diameter D, and biomass M will covary across phyletically diverse species. However, the relationships between scaling exponents and normalization constants remain unclear. Therefore, we developed a predictive model for the covariation of H, D, and stem volume V scaling relationships and used data from Chinese fir (Cunninghamia lanceolata) in Jiangxi province, China to test it. As predicted by the model and supported by the data, normalization constants are positively correlated with their associated scaling exponents for D vs. V and H vs. V, whereas normalization constants are negatively correlated with the scaling exponents of H vs. D. The prediction model also yielded reliable estimations of V (mean absolute percentage error = 10.5 ± 0.32 SE across 12 model calibrated sites). These results (1) support a totally new covariation scaling model, (2) indicate that differences in stem volume scaling relationships at the intra-specific level are driven by anatomical or ecophysiological responses to site quality and/or management practices, and (3) provide an accurate non-destructive method for predicting Chinese fir stem volume.

Motor Control Abnormalities in Parkinson’s Disease

PubMed Central

Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

2012-01-01

The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

Thyroid function during the spontaneous course of subacute thyroiditis

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

Teixeira, V.L.; Romaldini, J.H.; Rodrigues, H.F.

1985-05-01

A study of changes in serum T/sub 4/, T/sub 3/, and Tg as well as of serum TSH response to TRH was done in ten patients with subacute thyroiditis, from the acute phase up to 56 mo. All patients had symptoms of thyrotoxicosis. The mean serum T/sub 4/, T/sub 3/, and Tg concentration were significantly higher than in normal subjects. The basal TSH concentrations failed to increase in response to TRH. Mean serum T/sub 3/ and serum Tg levels remained higher than in normal subjects until 4 to 5 mo after the acute phase. Thyroid autoantibodies were absent during themore » whole period of study. An exaggerated response of TSH to TRH in six out of seven patients was observed from a 2 to 3 mo period until the end of follow-up. All patients with T/sub 3/ to T/sub 4/ ratio above the normal range (7-24 ng/..mu..g) showed also an exaggerated response of TSH to TRH. These data suggest that the spontaneous course of subacute thyroiditis may lead to a low thyroid reserve detectable even 5 yr following the acute phase of the disease.« less

TSH and prolactin responses to thyrotropin releasing hormone (TRH) and domperidone in patients with empty sella syndrome.

PubMed

Valensi, P; Combes, M E; Perret, G; Attali, J R

1996-05-01

The aim of this study was to investigate TSH and PRL response to TRH and domperidone, an antidopaminergic drug which does not cross the blood-brain barrier, in 16 patients with primary empty sella (PES) and either normal or elevated plasma PRL level and to compare it with the response observed in 8 patients with prolactinoma. In the patients with PES and hyperprolactinemia, the PRL response to TRH was significantly lower than in the controls and the patients with PES and normal PRL, which suggests there is impaired PRL synthesis and release in cases of PES with hyperprolactinemia. The TSH response to domperidone was significantly elevated in patients with PES and either normal or elevated PRL, as in patients with prolactinoma. The PRL response to domperidone was significantly reduced in patients with PES and hyperprolactinemia as in patients with prolactionoma. These results suggestthat in PES with prolactinoma the inhibiting dopaminergic tone is increased on the thyrotropic cells and reduced on the lactotropic cells in PES with elevated PRL and that some patients with PES might bear a microprolactinoma in the bottom of the sella which remained undetected by the CT scan.

Corticocortical feedback increases the spatial extent of normalization.

PubMed

Nassi, Jonathan J; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T

2014-01-01

Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a "normalization pool." Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing.

Corticocortical feedback increases the spatial extent of normalization

PubMed Central

Nassi, Jonathan J.; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T.

2014-01-01

Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a “normalization pool.” Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing. PMID:24910596

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China

PubMed Central

Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Background and Objective Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Methods Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels(≥14ng/L) and patients with normal hs-cTnT levels (<14ng/L). Results The final analysis involved 84 patients (31 males; mean age, 61.6±12.2years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Conclusion Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies. PMID:26849554

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

PubMed

Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L) and patients with normal hs-cTnT levels (<14 ng/L). The final analysis involved 84 patients (31 males; mean age, 61.6±12.2 years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.