Neuroendocrine regulation of adrenal 5'-monodeiodination during acute cold exposure in the rat. I. Effects of hypophysectomy

Circulating levels of T4, T3, corticosterone, noradrenaline, and adrenaline, as well as 5'-monodeiodinase activity (5'-MA) were measured in control and hypophysectomized rats acutely exposed to cold environment (15-120 min, 4 C). In addition to the well known activation of the sympathoadrenomedullary system and the hypothalamic-pituitary-adrenal and-thyroid axes, cold exposure was followed by a rapid and sustained increase of 5'-MA in the hypothalamus, and a byphasic course of activation in the adrenal gland in control rats. The adrenal rapid activation (30 min) corresponded to the medulla and the slower activation (120 min) to the cortex. Both, the basal adrenal 5'-MA and the response to cold in adrenal and hypothalamus were 2-fold higher in hypophysectomized rats compared to control. The time course of enzyme activation in these structures suggests that: 1) organ-specific increases in 5'-MA may be associated to a simultaneous rise in their metabolic and/or functional activity, 2) the triggering mechanisms involves an immediate sympathetic signal activating the hypothalamic-adrenal medulla response and a pituitary signal eliciting a slower adrenocortical response, and 3) the compensatory sympathetic hyperactivity after panhypopituitarism contribute to enhance both the adrenal enzyme basal activity and the hypothalamic and adrenal hyperresponse to cold stress.     

Physiologically stable F127-GO supramolecular hydrogel with sustained drug release characteristic for chemotherapy and photothermal therapy

A synthetic method for preparing a Pluronic F127 (F127)-stabilized graphene (GO) supramolecular hydrogel as a safe nanovehicle for combination treatment has been studied. Doxorubicin (DOX) as a model drug is non-covalently bound on the great surface area of GO due to strong π–π interaction, hydrophobic interaction, and the strongest hydrogen bonding. In vitro drug release experiments revealed that this F127-stabilized GO supramolecular hydrogel has a sustained drug release characteristic. Furthermore, the supramolecular hydrogel showed better in vitro antitumor ability under NIR (near infrared) laser irradiation because of the excellent photothermal effect of GO. Moreover, we evaluated its antitumor ability in vivo and the results show that the hydrogel system can also markedly inhibit the growth of a tumor when administered individually, especially under laser irradiation. All these findings make the supramolecular hydrogel system promising for combination therapy with good bioavailability and minimal side effects.

The F127-GO-DOX supramolecular hydrogel system with sustained drug release characteristic for chemotherapy and photothermal therapy.     

Survival and mortality among users and non-users of hydroxyurea with sickle cell disease

OBJECTIVE:

to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease.

METHOD:

cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05.

RESULTS:

of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause.

CONCLUSION:

the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions.     

Oxytocin levels in individuals with schizophrenia are high in cerebrospinal fluid but low in serum: A systematic review and meta-analysis

Metabolic Brain Disease - Schizophrenia is a debilitating mental illness. Levels of oxytocin have been proposed as a biomarker of schizophrenia; however, the observed levels of oxytocin in...     

Endothelins and markers of renal damage in recently diagnosed hypertensive patients

Endothelin has been identified as a potent vasoconstrictor. The aim of this study was to evaluate urinary endothelins and their relation to other markers of renal damage, such as microalbuminuria, creatinine, and N-acetyl-beta-glucosaminidase (NAG), in a group of recently diagnosed (less than 1 year) hypertensive subjects and a control group. We selected 50 subjects and divided them into two groups: 27 hypertensive patients (15 females and 12 males) without previous pharmacologic therapy, and 23 healthy, normotensive subjects (12 females and 11 males). All patients underwent a history and physical examination, chest x-ray, electrocardiography, funduscopy, and hematologic and biochemical analyses. Endothelins, microalbuminuria, creatinine, and NAG values were also determined in 24-hour urine samples. Creatinine, microalbuminuria, and NAG values were found to be higher in hypertensive than in normotensive subjects. The hypertensive group showed a nonsignificant elevation of total endothelin. In conclusion, the determination of elevated urinary endothelin does not appear to be an early marker of organ damage in hypertensive subjects. The urinary excretion of protein, creatinine, and NAG was higher in hypertensive subjects. A positive correlation was found between the urinary excretion of endothelins and markers of renal damage, microalbuminuria and NAG values. The relationship between endothelins and hypertension was without statistical significance.     

Protective role of melatonin and retinol palmitate in oxidative stress and hyperlipidemic nephropathy induced by adriamycin in rats

Abstract: We have studied the effects of melatonin and retinol palmitate (RP) on the nephropathy and oxidative stress induced by a single and high dose of adriamycin (AD) in Wistar male rats. A dose of melatonin (75 μg/ kg/day) and a dose of RP (0.25 g oily solution/kg/day, sc) were injected 3 and 9 days before and after the administration of AD (25 mg/kg, i.p.), respectively. After the decapitation, samples were taken from the neck vascular trunk in order to determine the triglycerides, total cholesterol, phospholipids, HDL-cholesterol, total proteins, urea, lipoperoxides, and reduced glutathione (GSH). We estimated the lipoperoxide and glutathione (GSH) contents in renal homogenates, and the excretion of proteins in urine over a 24 hr period. The administration of AD caused significant increases in proteinuria and in the other parameters studied [lipids (triglycerides, total cholesterol, phospholipids, and HDL-cholesterol), nonprotein nitrogen compounds, and lipoperoxides]. AD increased the lipoperoxide content, but it decreased the GSH content in the kidney. Both melatonin and RP, although melatonin more significantly, decreased the intensity of the changes produced by the administration of AD alone. In fact, melatonin was quite efficient in reducing the formation of lipoperoxides, restoring renal GSH content and decreasing remarkably the severity of proteinuria. These results support the powerful antioxidant action of melatonin at renal level and a lower antioxidant action of retinol. Likewise, these data reinforce the hypothesis which supports the pathogenetic role and the close relation between the oxidative stress and the expression of the nephropathy induced by AD. However, in spite of this obvious antioxidant effect of melatonin in the kidney, additional studies are required to establish accurately the role of this pineal indole in the regulation and dynamics of the antioxidative defense enzyme system, which neutralizes the damaging effect of free radicals, both endogenous and exogenous, in this organ.     

Colchicine for large pericardial effusion

On the basis of our reported experience with colchicine for recurrent pericarditis, we administered colchicine to two patients with large pericardial effusions complicating idiopathic pericarditis. The first was a 26-year-old male who showed clinical deterioration following emergency pericardiocentesis and aspirin (3 g/day) for 10 days; the second was a 2-year-old girl who was unsuccessfully treated with aspirin (100 mg/kg/day) for 2 weeks, followed by corti-costeroids for 7 months. Administration of colchicine (1 mg/ day) instead of aspirin in the first case, and with a rapid tapering-off of the corticosteroids in the second case, led to complete regression of the pericardial effusion on echocardiography within 1 week and 1 month, respectively. Colchicine was discontinued after 1 month in the first patient and was continued for 6 months in the child. Neither has had a recurrence at 24 and 6 months of follow-up, respectively. No side effects of colchicine were observed. We conclude that colchicine may be effective in the treatment of large pericardial effusion when therapy with nonsteroidal anti-inflammatory drugs and/or corticosteroids fails.     

Identification of the receptor for erythropoietin by cross-linking to Friend virus-infected erythroid cells.

Erythropoietin (Epo) is a glycoprotein hormone that regulates erythroid development and interacts with surface receptors on developing erythroid cells. In this laboratory, a cell system with a relatively pure population of erythroid cells that respond to Epo has been developed. Immature erythroid cells are obtained from the spleens of mice infected with the anemia strain of Friend virus. The binding of 125I-labeled Epo (125I-Epo) to plasma membranes from these cells was studied in this investigation. 125I-Epo binding reached equilibrium within 20 min at 37 degrees C. Twenty percent of the receptors bound 125I-Epo with a Kd of 0.08 X 10(-9) M, while the remaining receptors bound the hormone with a Kd of 0.6 X 10(-9) M. In this study, a receptor for Epo was identified by cross-linking 125I-Epo to the receptor in intact cells and plasma membrane preparations using disuccinimidyl suberate. Polyacrylamide gel electrophoresis revealed two labeled bands of 100 and 85 kDa. The 85-kDa band was more heavily labeled (65%) than the 100-kDa band. Both bands were equally decreased when increasing amounts of unlabeled Epo were included in the binding mixture, indicating a specific interaction of 125I-Epo with the receptor.     

Symptomatic gastrointestinal amyloidosis in an HIV-infected patient

We report a rare case of symptomatic GI amyloidosis in an HIV-infected patient who ultimately developed uncontrollable upper GI bleeding. Gastric and jejunal biopsies revealed amyloidosis. Although the patient's history suggested the possibility of secondary amyloidosis, immunohistochemical staining together with serum electrophoresis and immunofixation revealed the presence of lambda light chains indicating primary amyloidosis.     

Serum leptin levels in women with systemic lupus erythematosus

The purpose of this study was to evaluate serum leptin levels in systemic lupus erythematosus (SLE). Forty-one women with SLE were compared with 23 healthy women of similar age and body mass index (BMI). Clinical characteristics and Mexican systemic lupus erythematosus disease activity index (Mex-SLEDAI) score were assessed. Serum leptin levels (ng/dl) were measured by enzyme-linked immunosorbent assay (ELISA). Comparisons of leptin levels were made with the Mann-Whitney U-test. In a multiple regression analysis, those factors that could influence the leptin levels were adjusted. Patients with SLE had higher leptin levels than the control group (SLE median 31 vs control median 15, P=0.023). After adjusting by other variables, the serum leptin levels remained higher in SLE than in controls (P=0.02). Patients with SLE had no association between leptin levels and Mex-SLEDAI score, age, duration of disease, or prednisone doses. Those with SLE had higher leptin levels than controls. Further longitudinal studies are required to evaluate the role of this hormone in the exacerbations of SLE.