Intraoperative ultrasound (IOUS) images can be distorted by various artifacts. During surgeries for insular low-grade gliomas (LGGs), we repeatedly observed a distinct hyperechoic artifact adjacent ...to medial tumor borders, localized in brain regions with normal appearance on magnetic resonance imaging (MRI) that has not been reported before.
We retrospectively evaluated saved 3-dimensional (3D) IOUS images of 20 patients harboring insular LGGs. Twelve patients were operated on between 2010 and 2015 using an older navigated 3D IOUS system. Additionally, 3D-IOUS images of 8 patients operated on between 2021 and 2023 using a new high-end 3D-IOUS system were evaluated. The investigated region was the area under medial tumor borders, which were defined using preoperative MRI.
In 17 out of 20 cases (85%), a distinct hyperechoic area adjacent to medial tumor borders localized in brain regions with normal appearance on preoperative MRI was found; in the remaining 3 cases the saved images were suboptimal and did not allow evaluation of the area under the medial tumor borders.
Although the causes of this bright artifact are unclear, we can hypothesize that the reverberation in between different parallel layers of white and gray matter localized under the insula could play a role in its appearance. Importantly, as this hyperechoic area was depicted already before any tumor resection, it may lead to erroneous conclusion that the tumor spreads more medially. Potential resection in this region may cause significant neurologic sequelae.
While benefits of intraoperative ultrasound (IOUS) have been frequently described, data on IOUS limitations are relatively sparse. Suboptimal ultrasound imaging of some pathologies, various types of ...ultrasound artifacts, challenging patient positioning during some IOUS-guided surgeries, and absence of an optimal IOUS probe depicting the entire sellar region during transsphenoidal pituitary surgery are some of the most important pitfalls. This review aims to summarize prominent limitations of current IOUS systems, and to present possibilities to reduce them by using ultrasound technology suitable for a specific procedure and by proper scanning techniques. In addition, future trends of IOUS imaging optimization are described in this article.
The pregnane X receptor (PXR) was isolated as a xenosensor regulating xenobiotic responses. In this study, we show that PXR plays an endobiotic role by impacting lipid homeostasis. Expression of an ...activated PXR in the livers of transgenic mice resulted in an increased hepatic deposit of triglycerides. This PXR-mediated lipid accumulation was independent of the activation of the lipogenic transcriptional factor SREBP-1c (sterol regulatory element-binding protein 1c) and its primary lipogenic target enzymes, including fatty-acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC-1). Instead, the lipid accumulation in transgenic mice was associated with an increased expression of the free fatty acid transporter CD36 and several accessory lipogenic enzymes, such as stearoyl-CoA desaturase-1 (SCD-1) and long chain free fatty acid elongase. Studies using transgenic and knock-out mice showed that PXR is both necessary and sufficient for Cd36 activation. Promoter analyses revealed a DR-3-type of PXR-response element in the mouse Cd36 promoter, establishing Cd36 as a direct transcriptional target of PXR. The hepatic lipid accumulation and Cd36 induction were also seen in the hPXR “humanized” mice treated with the hPXR agonist rifampicin. The activation of PXR was also associated with an inhibition of pro-β-oxidative genes, such as peroxisome proliferator-activated receptor α (PPARα) and thiolase, and an up-regulation of PPARγ, a positive regulator of CD36. The cross-regulation of CD36 by PXR and PPARγ suggests that this fatty acid transporter may function as a common target of orphan nuclear receptors in their regulation of lipid homeostasis.
Organophosphate pesticide (OP) poisoning is quite common and can cause cardiovascular complications and even direct myocardial injury. However, no guideline has included an acute poisoning as a ...potential cause for a type 2 myocardial infarction (MI) so far. Here we present a case of a 61-year-old woman brought by ambulance to emergency department one hour after accidental ingestion of an unknown quantity of a solution she used against flea infestation. The patient presented with dizziness, myosis, excessive sweating, hypersalivation, sphincteric incontinence, muscle fasciculation, tremor of the extremities, pale skin, alcoholic and pesticide breath odour. Even though we had no guidelines to fall back on, we successfully treated the patient with low-molecular-weight heparin, antiplatelets, statin, diltiazem, antidote therapy, and supportive care. Physicians should be aware that OP poisoning can induce type 2 MI as a complication within a few hours since exposure, and emergency management should always include close cardiac monitoring.
The traditional Chinese medicines (TCMs) are essential components of alternative medicines. Many TCMs are known to alter the expression of hepatic drug-metabolizing enzymes and transporters. The ...molecular mechanism by which TCMs and/or their constituents regulate enzyme and transporter expression, however, has remained largely unknown. In this report, we show that two TCMs, Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch), and their selected constituents activate the xenobiotic orphan nuclear receptor pregnane X receptor (PXR). Treatment with TCM extracts and the Schisandrol and Schisandrin constituents of Wu Wei Zi induced the expression of drug-metabolizing enzymes and transporters in reporter gene assays and in primary hepatocyte cultures. The affected enzymes and transporters include CYP3A and 2C isozymes and the multidrug resistance-associated protein 2. In transient transfection and reporter gene assays, the Schisandrin constituents of Wu Wei Zi had an estimated EC50 of 2 and 1.25 microM on hPXR and mPXR, respectively. Interestingly, mutations that were intended to alter the pore of the ligand-binding cavity of PXR had species-specific effects on the activities of the individual Schisandrols and Schisandrins. In rats, the administration of Wu Wei Zi and Gan Cao increased the metabolism of the coadministered warfarin, reinforcing concerns involving the safe use of herbal medicines and other nutraceuticals to avoid PXR-mediated drug-drug interactions. Meanwhile, the activation of PXR and induction of detoxifying enzymes provide a molecular mechanism for the hepatoprotective effects of certain TCMs.
Cytosolic sulfotransferase (SULT)-mediated sulfation plays an essential role in the detoxification of bile acids and is necessary to avoid pathological conditions, such as cholestasis, liver damage, ...and colon cancer. In this study, using transgenic mice bearing conditional expression of the activated constitutive androstane receptor (CAR), we demonstrate that activation of CAR is both necessary and sufficient to confer resistance to the hepatotoxicity of lithocholic acid (LCA). Surprisingly, the CAR-mediated protection is not attributable to the expected and previously characterized CYP3A pathway; rather, it is associated with a robust induction of SULT gene expression and increased LCA sulfation. We have also provided direct evidence that CAR regulates SULT expression by binding to the CAR response elements found within the SULT gene promoters. Interestingly, activation of CAR was also associated with an increased expression of the 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2), an enzyme responsible for generating the sulfate donor 3'-phosphoadenosine-5'-phosphosulfate. Analysis of gene knockout mice revealed that CAR is also indispensable for ligand-dependent activation of SULT and PAPSS2 in vivo. Therefore, we establish an essential and unique role of CAR in controlling the mammalian sulfation system and its implication in the detoxification of bile acids.
•Preservation of LSAs is extremely important during resections of insular gliomas.•Navigated 3D-US power Doppler may enable intraoperative visualization of LSAs.•Quality of ultrasound scanner is ...important when LSAs should be visualized.•Reliability of LSAs depiction by 3D-US power Doppler is still investigated.
Efficient detoxification of bile acids is necessary to avoid pathological conditions such as cholestatic liver damage and colon cancer. The orphan nuclear receptors PXR and CAR have been proposed to ...play an important role in the detoxification of xeno- and endo-biotics by regulating the expression of detoxifying enzymes and transporters. In this report, we showed that the combined loss of PXR and CAR resulted in a significantly heightened sensitivity to bile acid toxicity in a sex-sensitive manner. A regimen of lithocholic acid treatment, which was tolerated by wild-type and PXR null mice, caused a marked accumulation of serum bile acids and histological liver damage as well as an increased hepatic lipid deposition in double knockout males. The increased sensitivity in males was associated with genotype-specific suppression of bile acid transporters and loss of bile acid-mediated downregulation of small heterodimer partner, whereas the transporter suppression was modest or absent in females. The double knockout mice also exhibited gene- and tissue-specific dysregulation of PXR and CAR target genes in response to PXR and CAR agonists. In conclusion, althoughthe cross-regulation of target genes by PXR and CAR has b een proposed, the current study represents in vivo evidence of the combined loss of both receptors causing a unique pattern of gene regulation that can be translated into physiological events such as sensitivity to toxic bile acids.
The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are implicated in xenobiotic and endobiotic detoxification, including the clearance of toxic bilirubin. Previous studies ...have suggested both overlapping and preferential regulation of target genes by these receptors, but the mechanism of cross-talk remains elusive. Here we reveal a dual role of PXR in bilirubin detoxification in that both the loss and activation of PXR led to protection from hyperbilirubinemia induced by bilirubin infusion or hemolysis. The increased bilirubin clearance in PXR-null mice was associated with selective upregulation of detoxifying enzymes and transporters, and the pattern of regulation is remarkably similar to that of transgenic mice expressing the activated CAR. Interestingly, the increased bilirubin clearance and associated gene regulation were absent in the CAR-null or double-knockout mice. In cell cultures, ligand-free PXR specifically suppressed the ability of CAR to induce the multidrug resistance associated protein 2 (MRP2), a bilirubin-detoxifying transporter. This suppression was, at least in part, the result of the disruption of ligand-independent recruitment of coactivator by CAR. In conclusion, PXR plays both positive and negative roles in regulating bilirubin homeostasis, and this provides a novel mechanism that may govern receptor cross-talk and the hierarchy of xenobiotic and endobiotic regulation. PXR is a potential therapeutic target for clinical treatment of jaundice. (HEPATOLOGY 2005;41:497-505.).
Organophosphate pesticide (OP) poisoning is quite common and can cause cardiovascular complications and even direct myocardial injury. However, no guideline has included an acute poisoning as a ...potential cause for a type 2 myocardial infarction (MI) so far. Here we present a case of a 61-year-old woman brought by ambulance to emergency department one hour after accidental ingestion of an unknown quantity of a solution she used against flea infestation. The patient presented with dizziness, myosis, excessive sweating, hypersalivation, sphincteric incontinence, muscle fasciculation, tremor of the extremities, pale skin, alcoholic and pesticide breath odour. Even though we had no guidelines to fall back on, we successfully treated the patient with low-molecular-weight heparin, antiplatelets, statin, diltiazem, antidote therapy, and supportive care. Physicians should be aware that OP poisoning can induce type 2 MI as a complication within a few hours since exposure, and emergency management should always include close cardiac monitoring. KEY WORDS: cardiovascular events; organophosphate poisoning; toxicology Otrovanje organofosfatnim pesticidima prilicno je cesto i moze dovesti do komplikacija sa srcem i krvoziljem, a ponekad i izravno ostetiti srcani misic. Do sada, medutim, nije zabiljezen slucaj infarkta miokarda tipa 2. U ovom je radu prikazan slucaj otrovanja 61-godisnjakinje koja je primljena u odjel hitne pomoci jedan sat nakon slucajnoga gutanja nepoznate kolicine otopine koju je upotrebljavala za suzbijanje biljnih usi. Bolesnica je primljena sa znakovima i simptomima osamucenosti, mioze, prekomjernoga znojenja, hipersalivacije, urinarne inkontinencije, misicne fascikulacije, drhtavice u udovima, bljedilom te dahom koji je mirisao na alkohol i pesticide. Premda nije bilo smjernica za lijecenje u takvom slucaju, primjena heparina niske molekulske mase, antitrombotika, statina, diltiazema, antidota i potpornoga lijecenja dovela je do povoljnog ishoda. Svrha je ovoga prikaza ukazati lijecnicima da otrovanje organofosfatima moze uzrokovati infarkt miokarda tipa 2, koji se javlja kao komplikacija unutar nekoliko sati od otrovanja, tako da obrada u odjelu hitne pomoci svakako treba obuhvatiti i strogi nadzor srcane funkcije. KLJUCNE RIJECI: kardiovaskularni dogadaji; pesticidi; toksikologija
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