1141610241Altered expression of HuR, an mRNA stabilizing protein, mediates aberrant Placenta Growth Factor (PlGF) expression in preeclampsia

Background:  Control of mRNA stability is an essential regulatory process in eukaryotic gene expression. HuR, a 3'UTR mRNA binding protein, can protect AU-rich mRNA from degradation in response to stresses. PlGF, an angiogenic growth factor, contains two consensus AU-rich sites suggesting that under normal conditions HuR may protect PlGF mRNA from degradation. Trophoblast expression of PlGF is significantly decreased in preeclampsia and by hypoxia in vitro . We hypothesize that decreased levels of cytoplasmic HuR may contribute to decreased PlGF expression in hypoxic and preeclamptic trophoblast.
Methods:  Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results:  Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions:  HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects.     

Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection.

BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.     

MORPHOLOGICAL AND BIOCHEMICAL STUDIES OF A CASE OF MUCOPOLYSACCHARIDOSIS II (HUNTER'S SYNDROME)

An autopsy case of a 19-year-old boy who had shown typical gargoyle features, strictly consistent with mucopolysaccharidosis type II (Hunter's syndrome) was reported. Histologically, cytoplasmic vacuolar change was found In hepatocytes, sinusoidal epithelium of spleen, follicular cells of thyroid, Sertoli cells of testis, chromophobe cell of pituitary and generalized fibroblast-like cells including meninges, cardiac valve and periosteum. The vacuoles consisting of membrane-bound structures with flocculus protein-like material and occasional electron dense bodies on electron microscopy, were considered to be the site of mucopolysaccharide deposition by histochemical analysis. Deposition of lipid material consistent with so-called membranous cytoplasmic body was observed in the neurons of central, peripheral and autonomic nervous system. Hepatosplenomegaly could be explained by cytoplasmic deposition, but the cause of cardiomegaly remained further to be studied. Biochemically hepatic mucopolysaccharide was identified as heparan sulfate, while in the kidney dermatan sulfate and heparan sulfate were detected. The correlation between morphology and biochemistry, and between deposition and degeneration was discussed.     

Metastatic tumors in the sellar and parasellar regions: clinical review of four cases

Metastatic tumors in the sellar and parasellar regions are uncommon and rarely detected in clinical practice. We present four cases of sellar and parasellar metastatic tumors, which metastasized from distant organ in one case and extended directly from adjacent structures in three. Common presenting symptoms were cranial neuropathies, headache and facial pain. Invasion into the cavernous sinus was noted in all cases. We report rare cases of sellar and parasellar metastases. Also, we should consider the possibility of metastasis in these regions for patients who showed the above clinical presentations in systemic cancer patients. In extensive diseases, transient symptomatic relief could be obtained by direct surgical management, even in restricted degree.     

Extraarticular synovial chondromatosis: review of epidemiology, imaging studies, microscopy and pathogenesis, with a report of an additional case in a child

A rare benign condition of uncertain etiology and pathogenesis, Synovial Chondromatosis (SC) is most often seen intraarticularly in adults but only a handful of cases have been reported extraarticularly in children. Symptoms and physical signs consist of pain, swelling, and osteoarthritic changes related to a mass effect. Here we discuss the case of a 9-year-old boy with documented SC of the knee and critically review the Epidemiology, Clinical Presentation, Gross Anatomy and Microscopic Histopathologic Features as well as the role of Imaging Studies in Diagnosis. In addition, this paper reviews Current Pathogenetic Concepts including the infrequent but distinct possibility of malignant transformation.     

Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy

Rett syndrome is a severe neurodevelopmental disorder that arises from mutations in the X-linked MECP2 gene. It is almost exclusively seen in girls due to the predominant occurrence of the mutations on the paternal X-chromosome, and also the early postnatal lethal effect of the disease causing mutations in hemizygous boys. We identified a boy with features of classic Rett syndrome who is mosaic for the truncating MECP2 mutation R270X. Chromosome analysis showed normal karyotype. These results indicate that a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism.     

Plasma lipids and lipoproteins and essential hypertension

In recent years there have been many studies demonstrating a correlation between increased arterial blood pressure and altered lipid profiles, and there has been an especially positive correlation between high cholesterol levels and blood pressure. There are differences between the various reports that are important. In our study the lipid distribution in 105 hypertensive patients with mild or moderate arterial hypertension according to WHO criteria without clinically or ultrasonographically apparent atherosclerosis was compared to the lipid distribution in 65 age-matched healthy persons. On the epidemiological level a significant, positive association was found between LDL serum levels (P 0.001), Apo B serum levels (P 0.001), serum triglyceride levels (P 0.05) and VLDL serum levels (P 0.01) and arterial hypertension. However, in contrast to recent reports, no significant difference was found between total serum cholesterol levels in normotensives and hypertensives, and there was no difference in HDL serum levels. No evidence could be found for a significant increase in lipoprotein (a) serum levels in hypertensives.Abbreviations LDL low density lipoprotein - VLDL very low density lipoprotein - HDL high density lipoprotein - Apo B 100 apolipoprotein B 100 - Apo A I apolipoprotein A I Correspondence to: H. Vetter     

Antiplatelet agents isolated from medicinal plants.

Platelet-vessel wall interaction is an important process in physiological hemostasis and pathological thrombosis. In oriental countries, some medicinal plants have been claimed for uses to improve circulation, induce fibrinolysis or prevent thrombosis. In cooperation with chemists using bioassay-based step-by-step purification, some antiplatelet agents were isolated from plant sources. According to their effects on platelet aggregation, release reaction and signal transductions involved, these antiplatelet agents can be classified into eight groups: 1. platelet-activating factor (PAF) antagonists, 2. collagen-receptor antagonists, 3. thromboxane-receptor antagonists, 4. ADP-receptor agonists, 5. inhibitors of phosphoinositide breakdown, 6. inhibitors of thromboxane formation, 7. agents increasing cyclic nucleotides, and 8. protein kinase C activators. These new pharmacological agents derived from medicinal plant sources may be useful as leads to develop as effective cardiovascular drugs.     

Chronic intracranial pressure monitoring by telemetry: Clinical experience

Intracranial pressure (ICP) monitoring is a critical measure for avoiding severe brain dysfunction or brain death by directing supportive therapy so as to prevent ICP increase severe enough to reduce cerebral blood perfusion. Such situations occur with brain swelling, increased cerebral vascular volume, and increase in cerebrospinal fluid (CSF) volume. Causes include ischemic stroke, subarachnoid bleeding, brain contusion, encephalitis (as in Reye's syndrome), and hydrocephalus from meningitis or neoplasm. When several days of ICP monitoring can direct resolution of the pressure crisis, the invasive direct connection of an intracranial sensor with external recording device carries only minimal infection risk. Prolonged ICP monitoring for weeks or months demands telemetry and becomes desirable in a number of chronic disease problems including both congenital and acquired hydrocephalus where enlarged and pressurized cerebral ventricles develop with reduced absorption of continuously secreted CSF. Although the primary disturbance in CSF circulation can remain incurable, its palliation by valve-regulated CSF diversions or shunting can restore normal brain function and in infants permit normal brain development. Missing this goal can result from failure to maintain a sufficiently normal pattern of CSF dynamics and ICP. Monitoring of the CSF pressure fluctuations transmitted through an intraventricular catheter provides the most accurate record of ICP pulsations. Therefore, a pressure sensing module can be “T'd” into an existing shunt system in continuity with the already placed ventricular tube. The capacity to monitor ICP accurately by telemetry was first established in dogs made hydrocephalic to assure free CSF pulse through a ventricular catheter (1,2,3, 4,5). The subsequent use of ICP monitoring by telemetry in three patients will be described.