Study of serum levels of superoxide dismutase in preeclampsia and eclampsia: role of the test as a predictive tool

AIM: To report serum levels of superoxide dismutase in women with preeclampsia and eclampsia. To document the use of the value as a predictive tool for deciding the time of onset of subsequent convulsions with fulminating eclampsia and use of the value as a marker for obstetric intervention in clinical severe preeclampsia and eclampsia. METHODS: Superoxide dismutase concentration was measured in a consecutive study in sera of women admitted in obstetric ward for preeclampsia and eclampsia, and compared with sera of normotensive, healthy pregnant women in third trimester. Three mL venous blood was subjected to superoxide dismutase estimation by pyrogallol autoxidation method. RESULTS: We found statistically significant difference (P < 0.05) in mean superoxide dismutase levels of normotensive pregnant women; and preeclamptic and eclamptic subjects, no statistically significant difference was found in between value of enzyme in preeclampsia and eclampsia (P > 0.05). Superoxide dismutase levels in two pregnancy outcomes; live births and still births, shows significant difference (P < 0.05), being 1.03 U/mL and 0.52 U/mL, respectively. The comparison of values before delivery and after delivery showed highly statistically significant difference (P < 0.001) in both groups separately. The cut-off value of serum superoxide dismutase 0.52 U/mL has sensitivity 68.5%, specificity 59.5% and negative predictive value of 78.6%, for predicting the fetal death as outcome of pregnancy with severe grade of disease. CONCLUSION: We found low levels of serum superoxide dismutase, less than 0.52 U/mL, being the predecessor of fulminating eclampsia. Our results support this predictive value of serum superoxide dismutase level as important in deciding the time of intervention as termination of pregnancy.     

Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses

Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here, we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts, identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses.     

Mutational effects on protein folding stability and antigenicity: the case of streptococcal pyrogenic exotoxin A

The influence of mutationally induced changes in protein folding on development of effective neutralizing antibodies during vaccination remains largely unexplored. In this study, we probed how mutational substitutions of streptococcal pyrogenic exotoxin A (SPEA), a model bacterial superantigen, affect native conformational stability and antigenicity. Stability changes for the toxin variants were determined using circular dichroism and fluorescence measurements, and scanning calorimetry. Self-association was assayed by dynamic light scattering. Inactivated SPEA proteins containing particular combinations of mutations elicited antibodies in HLA-DQ8 transgenic mice that neutralized SPEA superantigenicity in vitro, and protected animals from lethal toxin challenge. However, a highly destabilized cysteine-free mutant of SPEA did not provide effective immunity, nor did an irreversibly denatured version of an otherwise effective mutant protein. These results suggest that protein conformation plays a significant role in generating effective neutralizing antibodies to this toxin, and may be an important factor to consider in vaccine design.     

Alveolar distraction: analysis of 10 cases

OBJECTIVE: The purpose of this study was to evaluate intraoperative and postoperative complications of alveolar distraction and outcome. STUDY DESIGN: Ten patients with alveolar ridge deficiencies were treated with alveolar distraction osteogenesis by means of intraosseous distractors (Lead system, Stryker Leibenger, Kalamazoo, Mich). The deficiencies were caused by atrophy after periodontal disease or atrophy after tooth extraction (n = 6), benign tumor resection (n = 2), trauma (n = l), or oligodontia in a case of ectodermal dysplasia (n = l). The location of the defects was the anterior mandible (7), posterior mandible (1), and anterior maxilla (2). The mean follow-up was 1.8 years, with a range of 10 months to 3 years. RESULTS: The mean alveolar distraction achieved in 10 cases was 8.7 mm (5-15 mm). The intraoperative and postoperative problems encountered were lingual (n = 3) and palatal (n = 2) displacement of the distracted segment, fracture of the distracted segment in a very thin alveolar bone (n = 1), and intraoperative bleeding (n = 1). CONCLUSION: Overall complication rate was 70%. However, most of the complications were minor and eliminated easily. Implant success rate was 85%.     

Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans

The melanocortin-4 receptor gene (MC4-R) has been implicated in weight regulation. Recently, two independent groups reported frameshift mutations associated with a dominant form of obesity (1, 2). We screened the coding region of the MC4-R in 306 extremely obese children and adolescents (mean body mass index: BMI 34.4 +/- 6.6 kg/m2), 25 healthy underweight students (mean BMI 17.1 +/- 0.8 kg/m2), 52 normal weight individuals (mean BMI 22.0 +/- 1.0 kg/m2), 51 inpatients with anorexia nervosa (AN, DSM IV criteria, mean BMI 14.3 +/- 1.5 kg/m2) and 27 patients with bulimia nervosa (BN, DSM IV criteria, mean BMI 21.7 +/- 5.8 kg/m2) by single strand conformation polymorphism analysis (SSCP). Several mutations were identified, including the frameshift mutation described (1). The mutations were as follows: a) The deletion of 4 bp (delta of CTCT at codon 211) results in a frameshift, thus rendering a truncated protein. This mutation has been assumed to be associated with dominantly-inherited morbid obesity in humans (1). Both the index patient (BMI 42.06 kg/m2, height 171 cm, age 19.6 years) and her mother (BMI 37.55 kg/m2, height 164 cm, age 42.5 years) were heterozygous for the deletion. b) A nonsense mutation at position 35 of the MC4-R was detected in two obese probands (BMI 31.29 kg/m2 and BMI 45.91 kg/m2). This mutation leads to a truncated protein that encompasses the N-terminal extracellular domain. Both carriers additionally showed (c) a missense mutation (Asp-37-Val). In both of these cases Tyr-35-Stop and Asp-37-Val were maternally transmitted, thus these variations form a haplotype. d) e) A male obese proband harbored two missense mutations (Ser-30-Phe, Gly-252-Ser). f)-i) Four different missense mutations (Pro-78-Leu, Thr-112-Met, Arg-165-Trp, Ile-317-Thr) were detected in four different male probands, respectively. All of these mutations (a to i) were found solely in extremely obese individuals whose BMIs were all above the 99th percentile. j) A silent mutation (C-579-T, Val-193-Val) was detected in a male underweight individual. k) A previously described polymorphism (Val-103-Ile; 3) was detected with similar frequencies in all different study groups. 1) We identified a novel polymorphism (Ile-251-Leu) with similar allele frequencies in all groups under study. In conclusion, our data indicate that mutations in the MC4-R are not uncommon. Whereas our data support the evidence for dominantly inherited obesity as revealed by the three obese probands with haplo-insufficiency, the functional significance of the missense mutations remains to be determined.     

Gender Commonalities and Differences in the Neural Processing of Visual Sexual Stimuli

IntroductionFew studies so far have directly compared the neural processing of visual sexual stimuli in men and women. Also, most of these studies only compared sexual with neutral stimuli, making it difficult to disentangle sexual stimulus processing from general emotional processing.AimThe current study aimed to explore gender commonalities and differences in neural activity associated with the processing of visual sexual stimuli in a large sample of 50 men and 50 women. In order to disentangle effects of sexual processing from those of general emotional processing, we employed sexual, neutral, positive, and negative emotional pictures.MethodsSubjects passively viewed sexual, neutral, positive, and negative emotional pictures during a functional magnetic resonance imaging (fMRI) session. Pictures were presented in 24 blocks of five pictures each. Every block was rated immediately after its presentation with respect to valence, arousal, and sexual arousal.Main Outcome MeasuresBlood oxygen level dependent responses measured by fMRI and subjective ratings.ResultsfMRI analysis revealed a distributed network for the neural processing of sexual stimuli comprising the hypothalamus, the nucleus accumbens, as well as orbitofrontal, occipital, and parietal areas. This network could be identified (i) for both men and women, with men showing overall stronger activations than women and (ii) independent of general emotional arousal or valence effects.ConclusionOur data speak in favor of a common neural network associated with the processing of visual sexual stimuli in men and women. Apart from the observed gender commonalities, overall stronger responses in men were observed that might indicate stronger sexual responsivity in men     

An update on the role of PET/CT and PET/MRI in ovarian cancer

This review article summarizes the role of PET/CT and PET/MRI in ovarian cancer. With regard to the diagnosis of ovarian cancer, the presence of FDG uptake within the ovary of a postmenopausal woman raises the concern for ovarian cancer. Multiple studies show that FDG PET/CT can detect lymph node and distant metastasis in ovarian cancer with high accuracy and may, therefore, alter the management to obtain better clinical outcomes. Although PET/CT staging is superior for N and M staging of ovarian cancer, its role is limited for T staging. Additionally, FDG PET/CT is of great benefit in evaluating treatment response and has prognostic value in patients with ovarian cancer. FDG PET/CT also has value to detect recurrent disease, particularly in patients with elevated serum CA-125 levels and negative or inconclusive conventional imaging test results. PET/MRI may beneficial for tumor staging because MRI has higher soft tissue contrast and no ionizing radiation exposure compared to CT. Some non-FDG PET radiotracers such as ¹⁸F-fluorothymidine (FLT) or ¹¹C-methionine (MET) have been studied in preclinical and clinical studies as well and may play a role in the evaluation of patients with ovarian cancer.     

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia

Rational

A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia.

Objective

The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia.

Methods

In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8.

Results

Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699)?=?37.366, p?<?0.001] as well as negative scores [F(2.439,92.675)?=?16.623, p?<?0.001] and general psychopathology [F(1.767,67.158)?=?4.602, p?=?0.017], but not positive subscale scores [F(1.348, 51.218)?=?0.048, p?=?0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β?=??0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups.

Conclusion

Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.