Biomechanical and functional properties of trophoblast cells exposed to Group B Streptococcus in vitro and the beneficial effects of uvaol treatment.

BACKGROUND: Group B streptococcus (GBS) is the main bacteria that infects pregnant women and can cause abortion and chorioamnionitis. The impact of GBS effects on human trophoblast cells remains largely elusive, and actions toward anti-inflammatory strategies in pregnancy are needed. A potent anti-inflammatory molecule, uvaol is a triterpene from olive oil and its functions in trophoblasts are unknown. We aimed to analyze biomechanical and functional effects of inactivated GBS in trophoblast cells, with the addition of uvaol to test potential benefits. METHODS: HTR-8/SVneo cells were treated with uvaol and incubated with inactivated GBS. Cell viability and death were analyzed. Cellular elasticity and topography were accessed by atomic force microscopy. Nitrite production was evaluated by Griess reaction. Nuclear translocation of NFkB p65 was detected by immunofluorescence and Th1/Th2 cytokines by bead-based multiplex assay. RESULTS: GBS at 108 CFU increased cell death, which was partially prevented by uvaol. Cell stiffness, cytoskeleton organization and morphology were changed by GBS, and uvaol partially restored these alterations. Nuclear translocation of NFkB p65 began 15 min after GBS incubation and uvaol inhibited this process. GBS decreased IL-4 secretion and increased IL-1ß, IFN-γ and IL-2, whereas uvaol reverted this. CONCLUSIONS: The increased inflammation and cell death caused by GBS correlated with biomechanical and cytoskeleton changes found in trophoblast cells, while uvaol was effective its protective role. GENERAL SIGNIFICANCE: Uvaol is a natural anti-inflammatory product efficient against GBS-induced inflammation and it has potential to be acquired through diet in order to prevent GBS deleterious effects in pregnancy.

Comparative overview of brain perfusion imaging techniques.

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.

Speech activation SPECT and plasticity of language networks.

Neuronal activity might be measured by regional cerebral blood flow (rCBF) Single Photon Emission Computed Tomography (SPECT) as there is a close relationship between neuronal activity and rCBF changes. In order to study the hemispheric dominance for language and the plasticity of language networks by measuring the rCBF rest and language activation SPECT studies were performed in the presurgical evaluation of ten right-handed and two left handed patients with brain lesions of the dominant hemisphere. A special group of hemisphere-specific neuropsychologic tasks were used for activation, after a proper psychologic conditioning. The rCBF results were calculated by comparing the rest and activation SPECT data using a special regions of interest program and asymmetry index (AI). We compared the results of speech-activation to the results of clinical, morphological (MRI), and postoperative data. In controls, significant activation was found in Brodmann's area 44 and 45, contralateral cerebellum, superior middle and posterior temporal gyrus. In patients, additional regions of activation were seen in contralateral frontal and temporal regions, and in ipsilateral temporal region. AIs of the cerebellum demonstrated a negative correlation with hemispheric dominance for language. In conclusion, significant changes in rCBF in or adjacent to the eloquent areas with various patterns of rCBF changes of the additional regions demonstrate the close relationship between neuronal activity and cerebral blood flow, that can be measured by SPECT.

[Functional imaging (PET and SPECT) in epilepsy]. / Epilepszia funkcionális képalkotó (PET és SPECT) vizsgálata.

Epilepsy is one of the most prevalent neurologic disorders and affects approximately 1% of the population. Most complex seizures arise from the temporal lobes and the condition of 20-30% of these patients is refractory to medication. Many can be rendered seizure free with surgery. Epilepsy surgery requires accurate identification of the site and extent of the epileptogenic area responsible for seizures. EEG is accepted as a gold standard, however only 50% of the patients are safely diagnosed. The need for invasive monitoring with possible hemorrhage or infection has been greatly reduced by the introduction of new technologies such as PET, SPECT and MRI in the clinical practice. MRI demonstrate morphologic changes in approximately 80% of patients with epilepsy. However, structural lesions may not always correlate with clinical, EEG and pathologic localization of epileptogenic foci. Seizures are associated with pronounced changes in regional cerebral blood flow. The real power of SPECT lies in the opportunity of ictal examinations, with a sensitivity ranging from 90 to 97%. Interictal PET studies using 18F-FDG measure regional glucose metabolism, have been investigated for their value as non-invasive focus-localizing techniques. These studies have sensitivity ranging from 80 to 85%. The benzodiazepine binding site that are associated with and modulate the activity of GABA receptors have been imaged by SPECT (using 123I-iomazenil) and PET (using 11C-Flumazenil). Combined measurements of benzodiazepine binding sites and perfusion/metabolism provide a more accurate visualization of epileptogenic site than perfusion or metabolism measurements alone. Functional imaging modalities (PET and SPECT) are highly important in the presurgical evaluation of patients with medically refractory complex partial seizures.

[Functional neuroimaging in movement disorders]. / Funkcionális képalkotó vizsgálatok mozgászavarokban.

Positron Emission Tomography (PET) and Single Photon Emission. Computed Tomography (SPECT) highly contribute to the management of patients with movement disorders by measuring regional cerebral metabolism/blood flow and dopamine receptors. Imaging of the dopaminergic system is a powerful tool for distinguishing patients with neurodegenerative disorders, such as Parkinson's disease. Parkinsonism is most of the time caused by idiopathic Parkinson's disease. Considering the differences in therapeutic response and prognosis, differentiation between Parkinson's disease and "parkinsonism-plus syndromes" is important. Visualisation of pre- and post-synaptic D2 dopamine receptors by using receptor ligands helps to discriminate between Parkinson's disease and "parkinsonism-plus syndromes" as Parkinson's disease is a presynaptic disease. Early disease detection in subjects suspected at risk for developing Parkinson's disease has become possible using ligands for the dopamine transporter. Functional imaging modalities are useful in the management of patients with movement disorders, are able to monitor in an objective way the efficacy of new pharmacological therapies, can document the effect of neuronal grafting for Parkinson's disease, and delineate the progression of these diseases.

NMSP binding to dopamine and serotonin receptors in MPTP-induced parkinsonism: relation to dopa therapy.

We tested the hypothesis that N-methylspiperone binding to dopamine D2 receptors must be reduced when L-dopa therapy of parkinsonism augments the binding of dopamine to the receptors and improves the clinical state expressed by the Hoehn & Yahr stage. A patient with MPTP-induced parkinsonism underwent two positron emission tomographic studies of the D2-like dopamine receptors with N-[11C]methylspiperone (NMSP). The first study took place 3 days after cessation of the L-dopa medication, the second 5 days after its resumption. Noticeable clinical deterioration occurred during both studies, consistent with significant dopamine receptor blockade by NMSP and elevated NMSP binding in both scans. The dopa treatment did not reduce the NMSP binding. On the contrary, the rate of binding of NMSP (k3) was increased on-dopa, compared to off-dopa. The increase was consistent with the slightly greater dopamine receptor density estimated after resumption of the dopa therapy. The NMSP binding to serotonin receptors suggested lower synaptic serotonin on-dopa than off-dopa. The results are consistent with negative correlation between the Hoehn & Yahr stage and the amount of dopamine bound to dopamine D2 receptors. Low synaptic serotonin may explain the depression seen in some patients on dopa for Parkinson's disease.

[The place of positron-emission tomography in contemporary patient care]. / A pozitron emissziós tomográfia helye a korszerü betegvezetésben.

Positron emission tomography (PET) is a unique method offering physicians unrivaled access to in vivo quantitative measurements. The PET studies are useful in many areas of establishing primary diagnosis, differential diagnosis, planning and monitoring therapeutical efficacy. As a clinical tool it has been shown to increase diagnostic accuracy. Unlike anatomical imaging modalities, such as CT and MR, PET permits assessment of chemical and physiological changes related to any function. PET images demonstrate pathological change long before they would be revealed by other imaging modalities like CT and MR. It produces images of molecular level of physiological function which can be used to measure many vital processes, including glucose metabolism, blood flow and perfusion, receptorligand binding rates, and oxygen utilization. The PET studies provide useful diagnostic information which may alter patient management and reduce the total cost of patient care. PET studies have made critical contributions to more cost-effective patient management in four clinical disciplines: cardiology, neurology, psychiatry and oncology. Recently, the clinical indications for PET have increased dramatically. Since Hungary's first PET center has been established at the University Medical School in Debrecen many studies additionally demonstrate that PET reduces overall cost of medical care, because it increases the certainty of diagnosis and clinical stage of disease, and therefore eliminates the expense of unnecessary testing or treatment.

[Speech activation SPECT measurements in the determination of hemispheric dominance]. / Beszédaktivációs SPECT vizsgálatok a féltekei dominancia meghatározásában.

Cognitive activity leads to an increased regional cerebral blood flow (rCBF) and energy metabolism in both cerebral hemispheres. In order to assess the reliability of rCBF-SPECT measurements in hemispheric dominance (Broca's area) speech activation SPECT studies were performed in nine patients. Patients (men, n = 6; women, n = 3, mean age: 33.8 +/- 13.8 years) with diagnosis of epilepsy (n = 7) and AVM (n = 2) participated in the preoperative study. Two SPECT studies were performed in each case, one in rest, and one during speech activation. 740 MBq of 99mTc-HMPAO/ECD was injected and stereo TCD monitoring was performed during the three minutes of speech activation. The acquisition was performed by a dual-head ADAC Solus Epic Atlas SPECT camera (ADAC Laboratories, Milpitas, USA). RCBF SPECT measurements were analyzed visually and by a special region-of-interest (ROI) program. The hemispheric dominance profiles were established on the basis of the respective blood flow velocity values obtained by fTCD and cortical hyperperfusion measured by SPECT. The neuropsychological test battery, used in the present study, was developed in our institute. The results of rCBF-SPECT studies highly correlated with the lateralization of hemispheric dominance measured by fTCD. There was a significant increase of rCBF in the inferior posterior frontal cortex (Broca's area, p < 0.0003). The non-invasive speech activation rCBF-SPECT measurement is a highly reliable and useful method in the determination of hemispheric dominance. SPECT studies are especially useful in cases where the performance of fTCD measurements are impossible due to the lack of temporal bone window or occlusive cerebral arterial disease.

[First Hungarian experiences with positron emission tomography (PET) studies. Members of the PET working group]. / Elsö hazai tapasztalatok pozitron emissziós tomográfiás (PET) vizsgálatokkal. PET munkacsoport tagjai.

Diagnostic investigations commenced on the 28th of June 1994 in Hungary's and Central Europe's first PET Centre at the University Medical School of Debrecen. The Centre is equipped with a GE 4096 Plus whole body PET scanner. A metabolic tracer, 18F-deoxy-D-glucose (FDG), was used in the investigations. During the first 15 months 249 PET investigations were made in the Centre of which 242 were diagnostic and 7 normal subjects served as control for the patient studies with brain scans. The number of oncological indications (intra- and extracranial tumours, Hodgkin's lymphomas) was n = 105 (43.4% of the 242 diagnostic examinations), neurological investigations (without intracranial tumours) formed the dominant group (n = 117; 48.3%), whereas the number of cardiological indications was 20 (8.3%). The oncological studies included those of intracranial tumours (n = 76; 31.4%); thyroid tumours (n = 9; 3.7%); Hodgkin's lymphomas (n = 7; 2.9%) and other extracranial tumours (n = 13; 5.4%). The distribution of different neurological and psychiatric investigations was as follows: localization of focal epileptogen zone (n = 60; 24.8%); differential diagnosis of dementias (n = 30; 12.4%); exploration of cerebrovascular diseases (n = 10; 4.1%); and other neurological diseases (n = 17; 7.0%). The main objective of the cardiological PET investigations was the exploration of viable myocardium. The present paper overviews both the procedures (including administrative issues, as well) and the results of the first 249 FDG-PET investigations.

Treatment of cystic craniopharyngiomas with yttrium-90 colloid solution.

The authors analyzed long-term follow-up data to assess the value of intracavitary irradiation with stereotactically implanted beta-emitting radioisotope (90)Y-silicate colloid for the treatment of craniopharyngiomas. Fifty-seven craniopharyngiomas in 42 patients were selected for retrospective analysis. The yttrium-90 was implanted intracavitally, using computerized tomography-guided and three-dimensional stereotactic treatment planning. The cumulative dose aimed at the inner surface of the cyst wall was 300 Gy. An average of 75% shrinkage of the initial cyst volume was observed. In 18 cases the reduction was more than 91%, and the cyst disappeared totally in 11 cases. A 50% decrease in cyst volume was usually apparent between the 2nd and 4th months. A 70% decrease in cyst volume was seen by the 5th and 6th months and an 80% reduction by the 7th and 8th months. Cysts that were unchanged remained so throughout the observation period. The time course of volume reduction could be expressed mathematically by the formula of 0.73 X e(-0.62 X T) + 0.27, where "e" is the basic number of natural logarithm and "T" is the time expressed in months. Mean survival duration after intracavitary irradiation was 9.4 years. The shrinkage of the cyst was a consequence of fibrosis of the wall, as seen on histopathological examination. The neuroophthalmological prognosis was favorable only when the optic disc was normal or nearly normal at the time of the treatment. In the presence of preexisting optic atrophy, visual deterioration proved to be irreversible. The long-term results support the view that intracavitary (90)Y-irradiation is a noninvasive and very effective method of treatment for craniopharyngioma cysts. Because of the 1.1 mm half-life decay of beta irradiation, it cannot influence the solid part of the tumor; therefore, the best result can be expected in solitary cysts.

[Internal hydrocephalus and basal liquorrhea (radionuclide data)]. / Vnutrenniaia gidrotsefaliia i bazal'naia likvoreia (radionuklidnye dannye).

The paper shows the value of radionuclide cysternomyelography in the diagnosis of internal hydrocephalus concurrent with basal liquorrhea. The authors examined 1522 patients of whom 105 were found to have the pathology, this yielded radionuclide differential diagnostic criteria for this nosological entity. They proposed new technological conditions for enhancing its diagnostic value.

PET-fluorodeoxyglucose of cranial and spinal neuromas.

Five patients with eighth nerve, one with ninth nerve and one with cervical neuromas were studied with PET and [18F] fluorodeoxyglucose (FDG). Four of the patients had had surgery prior to the PET study, and six patients had subsequent surgery. All tumors were well-visualized on the PET images. Only one patient with bilateral acoustic neuroma exhibited tumor recurrence or growth after the PET study; these two lesions showed the highest FDG uptakes in the PET studies (tumor-to-cerebellum ratio of 0.93-0.98). All other tumors were relatively hypometabolic (tumor-cerebellum ratios of 0.43-0.65) and showed no tumor growth or recurrence during follow-up periods ranging from 5 to 8 yr. These results suggest that PET-FDG may be of value in the evaluation of cranial and spinal schwannomas.

Scintigraphic study of cerebrospinal fluid shunts.

This paper deals with experience gained in the study of patency of different types of shunt. Results of subsequent surgery are considered. Findings of 79 scintigraphic studies with radiotechnetium on 68 patients are presented. The method is simple, quick, easy to reproduce and means only moderate radiation load for the patient. Results obtained suggest that this study is a reliable diagnostic tool which can be used in a routine way.

Determination of nasal liquorrhoea by means of radionuclide cisternography.

Ninety-two radionuclide cisternographies were performed on 88 patients with suspected nasal liquorrhoea. To identify fistulae of both traumatic and non-traumatic aetiology, 40 MBq of 169Yb-EDTA was injected to a total volume of 2 ml into the subarachnoid space usually by the cisternal route, but in some cases lumbar routes were chosen. Sixty-seven positive findings were verified by surgery, whereas no surgery was performed in 8 positive cases due to spontaneous clinical healing of the rhinorrhoea. Seventeen patients were studied who did not exhibit actual clinical signs of liquorrhoea. In each case a normal cisternogram was obtained. These cases were not operated upon. Results suggest that this investigation is a simple and reliable diagnostic tool that causes only negligible discomfort to the patient.

Myeloscintigraphic diagnostics of intramedullary space occupying processes.

This paper concerns the importance of myeloscintigraphy. A study method is presented and the advantages of using 169 Yb-EDTA are discussed. Myeloscintigraphy seems to be a sensitive and reliable diagnostic tool as is shown by the correlation of study results with surgical findings of 23 patients with intramedullary tumors.