Intracellular bioaccumulation of the rare earth element Gadolinium in ciliate cells resulting in biogenic particle formation and excretion.

Ciliates are abundant unicellular organisms capable of resisting high concentrations of metal ions in the environment caused by various anthropogenic activities. Understanding the cellular pathways involved in resistance to and detoxification of elements is required to predict the impact of ciliates on environmental element cycles. Here, we investigated the so far unknown process of tolerance, cellular uptake and bioaccumulation of the emerging rare earth element gadolinium (Gd) in the common ciliate Tetrahymena pyriformis. Gd treatment results in the intracellular formation and excretion of biogenic Gd-containing particles. This cellular process effectively removes dissolved Gd from the organic growth medium by 53.37% within 72 h. Based on light and electron microscopic observations, we postulate a detoxification pathway: Cells take up toxic Gd3+ ions from the medium by endocytosis, process them into stable Gd-containing particles within food vacuoles, and exocytose them. Stable biogenic particles can be isolated, which are relatively homogeneous and have a diameter of about 3 µm. They consist of the elements Gd, C, O, P, Na, Mg, K, and Ca. These findings broaden the view of metal ion accumulation by protists and are of relevance to understand environmental elemental cycles and may inspire approaches for metal recovery or bioremediation.

Angiosarcoma on Top of a Meningioma Mimicking a Transosseous Meningioma: an Interdisciplinary Point of View.

Cutaneous angiosarcoma is a rare type of sarcoma with poor prognosis. Meningioma is the most frequent benign intracranial tumor. Despite the fact that meningiomas are mostly benign, bone and skin can be infiltrated. We report the rare case of an angiosarcoma on top of a meningioma with hyperostosis at exactly the same location mimicking a transosseous growth of a meningioma. An 84-year-old man presented with progressive swelling and ulcerous lesion of the forehead. The patient underwent surgery in an interdisciplinary setting together with a plastic surgeon, including resection of the intracranial tumor and infiltrated bone and skin. To the best of our knowledge, this is the only reported case of a meningioma and angiosarcoma in direct neighborhood. A preoperative biopsy of the skin tumor would have led initially to the correct diagnosis of an angiosarcoma and would have allowed a better planning of the operation and extent of resection.

Resolution of Brainstem Edema after Neurosurgical Occlusion of Dural Arteriovenous Fistulas of the Craniocervical Junction: Report of Three Cases and Review.

OBJECTIVE: Dural arteriovenous fistulas of the craniocervical junction are rare but the most dangerous of spinal fistulas. The concurrent brainstem edema has been attributed to increased pressure within the venous outflow of the brainstem and upper cord, but the differential diagnosis of brainstem edema is demanding. This report presents the details of clinical findings, magnetic resonance imaging (MRI) , surgical techniques, and follow-up of these fistulas. METHODS: Three cases with dural arteriovenous fistulas and edema of the brainstem and upper cord are described plus a review of the literature. Clinical presentation, radiologic findings, and a follow-up of outcomes are presented. RESULTS: All three cases with misleading diagnoses at the time of referral experienced variable degrees of tetraparesis with brainstem edema on MRI. Congested veins on MRI raised the suspicion of a vascular origin of the edema. The diagnosis was established with highly specific angiography with microcatheters identifying a feeder from the ascending pharyngeal artery in two cases and a tentorial feeder from the carotid artery in one case. The operation included temporary clipping of the fistula and neuromonitoring. Follow-up confirmed improvement of clinical signs and resolution of the brainstem edema on MRI. CONCLUSION: Edema of the brainstem and cervical cord may be caused by a dural arteriovenous fistula of the craniocervical junction. Surgical occlusion may be an efficient option for the complete resolution of radiologic and clinical symptoms.

Structural brain alterations in patients with lumbar disc herniation: a preliminary study.

Chronic pain is one of the most common health complaints in industrial nations. For example, chronic low back pain (cLBP) disables millions of people across the world and generates a tremendous economic burden. While previous studies provided evidence of widespread functional as well as structural brain alterations in chronic pain, little is known about cortical changes in patients suffering from lumbar disc herniation. We investigated morphometric alterations of the gray and white matter of the brain in patients suffering from LDH. The volumes of the gray and white matter of 12 LDH patients were determined in a prospective study and compared to the volumes of healthy controls to distinguish local differences. High-resolution MRI brain images of all participants were performed using a 3 Tesla MRI scanner. Voxel-based morphometry was used to investigate local differences in gray and white matter volume between patients suffering from LDH and healthy controls. LDH patients showed significantly reduced gray matter volume in the right anterolateral prefrontal cortex, the right temporal lobe, the left premotor cortex, the right caudate nucleus, and the right cerebellum as compared to healthy controls. Increased gray matter volume, however, was found in the right dorsal anterior cingulate cortex, the left precuneal cortex, the left fusiform gyrus, and the right brainstem. Additionally, small subcortical decreases of the white matter were found adjacent to the left prefrontal cortex, the right premotor cortex and in the anterior limb of the left internal capsule. We conclude that the lumbar disk herniation can lead to specific local alterations of the gray and white matter in the human brain. The investigation of LDH-induced brain alterations could provide further insight into the underlying nature of the chronification processes and could possibly identify prognostic factors that may improve the conservative as well as the operative treatment of the LDH.

Controversies of diffusion weighted imaging in the diagnosis of brain death.

Imaging techniques as confirmatory tests may add safety to the diagnosis of brain death, but are partly not accepted either because they are too invasive, such as conventional arterial angiography, or because there is still lack of evidence of its reliability, such as magnetic resonance angiography. In this study the reliability of diffusion weighted imaging for the diagnosis of brain death was evaluated according in terms of its sensitivity and specificity. The apparent diffusion coefficients (ADC) of 18 brain dead patients were registered from 14 distinct brain areas. The mean ADC values of the brain dead patients were compared with normal controls of physiological ADC values of unaffected brain tissue. Despite a highly significant decrease of the mean ADC value in 16 patients, two patients showed mean ADC values that were within normal physiological range. An explanation may be the pseudonormalization of ADC values seen in stroke patients that depends on the time of the onset of the brain damage. We conclude, diffusion-weighted imaging may provide additional information on damage of the brain tissue but is not a practicable confirmatory test for the reliable diagnosis of brain death.

Determination of cerebrospinal fluid concentrations of arginine and dimethylarginines in patients with subarachnoid haemorrhage.

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), are assumed to be related to delayed vasospasm after subarachnoid haemorrhage (SAH). However, data on CSF concentrations of L-arginine, ADMA and its structural isomer symmetric dimethylarginine (SDMA) are very sparse in humans. We here present a new hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS-MS) method for the precise determination of these substances in CSF. The method requires only minimal sample preparation and features isotope labeled internal standards. First data of patients with SAH showed that on the day of admission CSF concentration values of L-arginine and ADMA were not significantly different from controls, but increased markedly during the course of the hospital stay. The decrease of the L-arginine to ADMA ratio points to a progressive impairment of the NO production rate in the brain after SAH which is confirmed by a simultaneous decrease in nitrate and nitrite concentrations in CSF.

The influence of a mouthpiece and noseclip on breathing pattern at rest is reduced at high altitude.

The effects of the instrumentation by a mouthpiece (MP) and a noseclip (NC) on the ventilatory response to short time hypobaric hypoxia were studied in 10 healthy volunteers at rest. The subjects were exposed to simulated altitude of 500 m, 3000 m, 4000 m and again 500 m, each altitude being applied for 30 min in a hypobaric chamber. Resting minute ventilation (VE), tidal volume (VT) and respiratory frequency (fR) using inductive plethysmography were continuously measured in all subjects in a standardized half lying position. The recordings were carried out at each altitude during the first 10 min without MP and NC, then 10 min with them, and the last 10 min again without them. At 500 m during MP+NC breathing VE and VT were increased, whereas fR was not significantly changed. At 3000 m, the VE increase with MP+NC was no more significant and fR was decreased. These effects of MP+NC on respiration disappeared at 4000 m and reappeared after the descent to 500 m. Furthermore, with and without MP and NC the variability of VE at 4000 m was significantly higher than at 500 m before ascent, and in all altitudes the variability of VT was significantly reduced by the MP+NC. It is concluded that the influence of MP+NC on VE, VT and fR is reduced or even abolished at high altitude, whereas the hypoxia induced increase of VE variability is not affected by the instrumentation.

Increased expression of ADAM family members in human breast cancer and breast cancer cell lines.

PURPOSE: ADAMs (A Disintegrin and Metalloprotease) are multifunctional, membrane-bound cell surface glycoproteins, which have numerous functions in cell growth, differentiation, and motility. We wished to investigate the expression of ADAM 9, 10, 12, 15, and in human breast cancer. METHODS: Expression of ADAMs was determined in breast cancer specimens and the corresponding non-neoplastic breast tissue from 24 patients, and in the MCF-7 and MDA-MB 453 breast cancer cell lines via quantitative RT-PCR and immunohistochemistry. The effects of anti-ADAM antibodies on cell proliferation were assessed by measuring DNA-synthesis. RESULTS: Breast cancer tissue samples showed increased mRNA expression of ADAM 9, 12, and 17, whereas ADAM 10 and 15 were not differently expressed. Protein expression was studied by immunohistochemistry. All ADAMs were expressed in MCF-7 and MDA-MB453 cell lines, with the highest expression levels being observed for ADAM 9, 12, and 17. Application of anti-ADAM 15 and anti-ADAM 17 antibodies significantly inhibited the proliferation of both MCF-7 and MDA-MB453 breast cancer cell lines. In contrast, the growth of MCF-7 cells appeared to be stimulated by the administration of anti-ADAM 12 antibody. CONCLUSION: The results of this study suggest that ADAMs are differentially expressed in human breast cancer and are capable of modulating tumour cell growth.

Gender differences in workload effect on coordination between breathing and cycling.

PURPOSE: To investigate the gender differences in the effect of increasing workload level and thus of an increasing metabolic drive to ventilation on the degree of coordination between breathing and cycling rhythms. METHODS: Twenty-one men and 21 women cycled on an electromagnetically braked ergometer while breathing through a pneumotachograph at workloads corresponding to 55, 75, and 95% of V0(2peak) (WL1, WL2, and WL3). Leg movements, respiratory parameters, and heart rate were continuously recorded. The degree of coordination (%coord) was quantified as the percentage of breaths starting during the same phase of leg movement. RESULTS: In men, %coord increased with increasing exercise intensity (WL1: mean +/- SE = 18.8 +/- 2.6%, WL2: 30.9 +/- 4.9%, WL3: 40.9 +/- 5.6%), whereas in women exercise intensity had no influence on %coord (WL1: 25.0 +/- 5.0%, WL2: 29.7 +/- 5.1, WL3: 31.7 +/- 4.7%). There were no gender differences in breathing pattern during high metabolic demands. A major effect on %coord came from the regularity of the breathing rhythm, whereas cycling frequency, fitness level, or cycling experience exerted no influence. CONCLUSIONS: The present study demonstrates that the effect of exercise intensity on the occurrence of coordination between breathing and cycling rhythms differs between men and women.

Influence of hypoxia on coordination between breathing and cycling rhythms in women.

To investigate interactions between neural (movement) and chemical (hypoxia) respiratory drives during exercise, we analyzed coordination between breathing and cycling rhythms in normoxia (N) and hypoxia (H, 14.5% O(2)). Twenty women [28 (1) years old] cycled for 6 min at three workloads (55%, 75%, and 95% peak oxygen consumption, VO(2peak); WL1, WL2, and WL3) in N and H. Leg movements, respiratory parameters, peripheral oxygen saturation, and heart rate were continuously recorded. The degree of coordination (%COORD) was quantified as the percentage of breaths starting during the same phase of leg movement. Ventilatory response to isocapnic hypoxia (VRH) was assessed at rest during an exposure to an end-tidal PO(2) of 50 mmHg. There were no differences in %COORD between N and H at any of the three workloads, but %COORD increased significantly from WL1 to WL3 in H. There was no correlation between VRH and %COORD. In conclusion, chemical and neural respiratory drives did not competitively interact: coordination between breathing and cycling rhythms was not reduced during H and did not depend on individual VRH.

Characteristics of the ventilatory response in subjects susceptible to high altitude pulmonary edema during acute and prolonged hypoxia.

The present study compares the changes in ventilation in response to sustained hypobaric hypoxia and acute normobaric hypoxia between subjects susceptible to high altitude pulmonary edema (HAPE-S) and control subjects (C-S). Seven HAPE-S and five C-S were exposed to simulated high altitude of 4000 m for 23 h in a hypobaric chamber. Resting minute ventilation (V(E)), tidal volume (V(T)), and respiratory frequency (f(R)), as well as the end-tidal partial pressures of oxygen (P(ET(O2))) and carbon dioxide (P(ET(CO2))) were measured in all subjects sitting in a standardized position. Six measurement periods were recorded: ZH1 at 450 m at Zurich level, HA1 on attaining 3600 m altitude, HA2 after 20 min at 4000 m, HA3 after 21 h and HA4 after 23 h at 4000 m altitude, and ZH2 immediately after recompression to Zurich level. At ZH1 and HA3, the measurements were first done in lying, then in sitting, and afterwards in standing. Peripheral arterial oxygen saturation (Sa(O2)) was continuously recorded. All respiratory parameters were also measured during exercise lasting 30 min, the work load being 50% of maximal oxygen consumption (V(O2max)) at Zurich level and 26% of the Zurich V(O2max) at 4000 m. V(E), P(ET(O2)) and P(ET(CO2)) did not significantly differ between HAPE-S and C-S at rest and during exercise periods at Zurich level and at high altitude. However, Sa(O2) was significantly lower in HAPE-S than in C-S at rest and during exercise at 4000 m. Breathing through the mouthpiece during ventilation measurements increased significantly the Sa(O2) in HAPE-S in posture tests at HA3. This effect was most pronounced in the supine posture, in which HAPE-S had the lowest Sa(O2) values. These data provide evidence that (1) gas exchange might be impaired on the level of ventilation-perfusion mismatch or due to diffusion limitation in HAPE-S during the first 23 h of exposure to a simulated altitude of 4000 m, and (2) contrary to C-S, the Sa(O2) in HAPE-S is significantly affected by body position and by mouthpiece breathing.