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International Journal of Molecular... Jan 2024A hypercaloric fatty diet predisposes an individual to metabolic syndrome and cardiovascular complications. Sirtuin1 (SIRT1) belongs to the class III histone deacetylase...
A hypercaloric fatty diet predisposes an individual to metabolic syndrome and cardiovascular complications. Sirtuin1 (SIRT1) belongs to the class III histone deacetylase family and sustains anabolism, mitochondrial biogenesis, and fat distribution. Epididymal white adipose tissue (eWAT) is involved in inflammation, whilst interscapular brown adipose tissue (iBAT) drives metabolism in obese rodents. Melatonin, a pineal indoleamine, acting as a SIRT1 modulator, may alleviate cardiometabolic damage. In the present study, we morphologically characterized the heart, eWAT, and iBAT in male heterozygous SIRT1 mice (HET mice) on a high-fat diet (60%E lard) versus a standard rodent diet (8.5% E fat) and drinking melatonin (10 mg/kg) for 16 weeks. Wild-type (WT) male C57Bl6/J mice were similarly fed for comparison. Cardiomyocyte fibrosis and endoplasmic reticulum (ER) stress response worsened in HET mice on a high-fat diet vs. other groups. Lipid peroxidation, ER, and mitochondrial stress were assessed by 4 hydroxy-2-nonenal (4HNE), glucose-regulated protein78 (GRP78), CCAA/enhancer-binding protein homologous protein (CHOP), heat shock protein 60 (HSP60), and mitofusin2 immunostainings. Ultrastructural analysis indicated the prevalence of atypical inter-myofibrillar mitochondria with short, misaligned cristae in HET mice on a lard diet despite melatonin supplementation. Abnormal eWAT adipocytes, crown-like inflammatory structures, tumor necrosis factor alpha (TNFα), and iBAT whitening characterized HET mice on a hypercaloric fatty diet and were maintained after melatonin supply. All these data suggest that melatonin's mechanism of action is strictly linked to full SIRT1 expression, which is required for the exhibition of effective antioxidant and anti-inflammatory properties.
Topics: Male; Animals; Mice; Diet, High-Fat; Melatonin; Sirtuin 1; Cardiovascular Diseases; Dietary Supplements
PubMed: 38255934
DOI: 10.3390/ijms25020860 -
The Journal of Craniofacial Surgery Feb 2024Sylvian aqueduct syndrome is a rare complication after ventriculoperitoneal (V-P) shunt surgery and is not easily diagnosed.
BACKGROUND
Sylvian aqueduct syndrome is a rare complication after ventriculoperitoneal (V-P) shunt surgery and is not easily diagnosed.
METHODS
A 26-year-old male with obstructive hydrocephalus due to tectal glioma was treated with a V-P shunt surgery in another hospital. After the surgery, the patient developed an intractable disturbance of consciousness. When the V-P shunt pressure was raised or lowered, the patient's consciousness disorder still could not be improved. The patient was diagnosed with Sylvian aqueduct syndrome, a rare complication after V-P shunt operation.
RESULTS
The paper clarifies the treatment experience with simultaneous endoscopic third ventriculostomy (ETV) and tectum gliomas biopsy, postoperative pathology suggestive of fibrillary astrocytoma; after surgery, the Sylvian aqueduct syndrome was cured and the patient recovered well.
CONCLUSIONS
The preferred treatment for obstructive hydrocephalus caused by tumors in the Pineal region is the ETV operation. If an ETV operation and biopsy operation are performed simultaneously, more details need to be noted.
PubMed: 38363289
DOI: 10.1097/SCS.0000000000010060 -
Journal of Neurosurgery. Case Lessons Mar 2024Bifocal germ cell tumors, with primarily identical tissue composition, occur concurrently in the neurohypophyseal and pineal regions.
BACKGROUND
Bifocal germ cell tumors, with primarily identical tissue composition, occur concurrently in the neurohypophyseal and pineal regions.
OBSERVATIONS
A 16-year-old male patient exhibited increased intracranial pressure symptoms, with concurrent tumors in the pineal and neurohypophyseal regions, causing obstructive hydrocephalus. His serum human chorionic gonadotropin level was elevated, measuring 506.6 mIU/mL. Upon gross endoscopic examination, the pineal tumor appeared white, whereas the neurohypophyseal tumor appeared red and hemorrhagic. Because of the limited sample size of the latter, a frozen section biopsy was feasible only for the pineal lesion, which indicated the presence of a germinoma. Subsequently, carboplatin and etoposide were administered, resulting in the reduction of the pineal tumor, but no effect was observed in the neurohypophyseal tumor. Histopathological analysis confirmed the pineal lesion as a germinoma, whereas the neurohypophyseal lesion was an embryonal carcinoma. Thus, the treatment was altered to ifosfamide, carboplatin, and etoposide (ICE), leading to a response in both tumors. The patient underwent three additional cycles of ICE therapy and high-dose chemotherapy, followed by whole craniospinal irradiation, achieving complete remission.
LESSONS
Although most bifocal germ cell tumors share the same histological tissue, occasional differences may arise, necessitating separate biopsies for accurate assessment.
PubMed: 38437676
DOI: 10.3171/CASE23718 -
Child's Nervous System : ChNS :... Sep 2023Pineal tumours (PTs) are rare and histologically variable. Serum melatonin is a well-known product of this gland, albeit with uncertain clinical implications vis-à-vis...
INTRODUCTION
Pineal tumours (PTs) are rare and histologically variable. Serum melatonin is a well-known product of this gland, albeit with uncertain clinical implications vis-à-vis its utility as a potential tumour marker. In particular, the temporal profile of serum melatonin during the disease course remains unclear and infrequently studied.
METHODS
Ten children with pineal tumours were prospectively studied over 2 years. Midnight serum melatonin levels were estimated before and after surgery (6-week postoperatively) and at the time of clinical-radiological progression. Different clinical, radiological, histological and treatment variables were correlated with the mean change in the pre- and postoperative serum melatonin levels using statistical methods.
RESULTS
Histopathologically, 5 of these cases (50%) were pineal cell tumours, while the rest were tumours of non-pineal cell origin. The mean preoperative serum melatonin level was 94.9 pg/ml (range 20-397 pg/ml), while the mean postoperative level was 69.6 pg/ml (range 45-156 pg/ml; in one case, the levels became non-detectable). Tumour histology (p = 0.04) and gender (p = 0.03) correlated with high preoperative serum levels. While the change in overall mean value did not have any statistical significance (effect size 0.29, p value 0.340), postoperative serum melatonin elevation was significant in tumours of non-pineal cell origin (large effect size 0.93, p value 0.004).
CONCLUSION
The serum melatonin may be affected by age, gender and symptom duration. However, the dynamic of serum melatonin in the perioperative period is largely dependent on the cell of origin of the PT.
Topics: Child; Humans; Melatonin; Pinealoma; Pineal Gland; Supratentorial Neoplasms; Brain Neoplasms; Circadian Rhythm
PubMed: 36045301
DOI: 10.1007/s00381-022-05601-9 -
World Neurosurgery Apr 2024A pineal region tumor is a rare intracranial tumor, and its specific location leads to its own characteristics. This study aimed to provide some insight for medical...
BACKGROUND
A pineal region tumor is a rare intracranial tumor, and its specific location leads to its own characteristics. This study aimed to provide some insight for medical practice in the care of pineal region tumors. We investigated the key epidemiological characteristics and survival prognosis of pineal tumors based on the epidemiological data from the Surveillance, Epidemiology, and End Results database.
METHODS
Data of pineal region tumor patients from 1975 to 2019 were extracted from the Surveillance, Epidemiology, and End Results database. The data were divided into 3 pathologic groups: germ cell tumors, pineal parenchymal tumors, and other. The patients' overall survival (OS) was analyzed using the Kaplan-Meier method. The prognostic effects of the patient characteristics on OS were explored using the Cox proportional hazard model. The analysis results are presented as tabular data, Kaplan-Meier plots, forest plots, and nomograms. A calibration curve was used to verify the nomograms. All analyses were performed for all patients overall and stratified by pathological group using SPSS and R language.
RESULTS
Based on the predefined inclusion and exclusion criteria, 628 patients were included in this study, of whom 440 (70.1%) were male and 188 (29.9%) were female. Most patients were aged 0-19 years. The pathological type was germinoma for 225 patients (35.8%). Age, surgery, behavioral code, and pathology were significant factors for OS. A calibration curve was used to verify that the nomograms had a good prediction effect.
CONCLUSIONS
An intuitive nomogram was developed and verified and can predict the prognosis of patients with pineal tumors.
Topics: Humans; Male; Female; Pinealoma; Neoplasm Staging; Retrospective Studies; SEER Program; Prognosis; Nomograms; Brain Neoplasms; Pineal Gland
PubMed: 38266997
DOI: 10.1016/j.wneu.2024.01.088 -
Journal of Translational Medicine Jan 2024Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment...
BACKGROUND
Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood.
METHODS
In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells.
RESULTS
Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy.
CONCLUSION
The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.
Topics: Antigens, CD19; Cell- and Tissue-Based Therapy; Cytokine Release Syndrome; Immunologic Factors; Immunotherapy, Adoptive; Melatonin; Neoplasm Recurrence, Local; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; Animals; Mice
PubMed: 38221609
DOI: 10.1186/s12967-023-04779-z -
World Neurosurgery: X Apr 2024The supra-cerebellar infratentorial approach to pineal region tumours is versatile and safe corridor to lesions located below the deep veins. Monitoring of the...
BACKGROUND
The supra-cerebellar infratentorial approach to pineal region tumours is versatile and safe corridor to lesions located below the deep veins. Monitoring of the extra-ocular muscle pathways using the evoked compound muscle action potential can lead to safer resections.
TECHNICAL NOTE
To describe the use of electrooculography and a three handed retractor less method for pineal region tumour surgeries.
MATERIAL AND METHODS
Intraoperative electrooculography uses recording done from two channels (horizontal and vertical)by inserting disposable subdermal needle electrodes along the periorbital area. The oculomotor nerve is being monitored as it exits the midbrain. Retractor-less three-handed-technique allows for minimal handling of the cerebellum while maximizing the operative corridor.
RESULT
The oculomotor nerve was stimulated post resection and correspondingly led to improved symptoms post-operatively.
DISCUSSION AND CONCLUSION
We demonstrate a method for the intraoperative monitoring of the continuity of the oculomotor tracts and a three handed retractor-less method of resection of pineal region tumours. The placement of electrodes and area of stimulation need sound knowledge of anatomy of the region. Haemostasis at every step is absolutely essential to be able to visualize in the narrow corridor.
PubMed: 38455252
DOI: 10.1016/j.wnsx.2024.100292 -
Journal of Clinical Medicine Feb 2024Pineal parenchymal cell tumors constitute a rare group of primary central nervous system neoplasms (less than 1%). Their classification, especially the intermediate... (Review)
Review
BACKGROUND
Pineal parenchymal cell tumors constitute a rare group of primary central nervous system neoplasms (less than 1%). Their classification, especially the intermediate subtype (PPTIDs), remains challenging.
METHODS
A literature review was conducted, navigating through anatomo-pathological, radiotherapy, and neurosurgical dimensions, aiming for a holistic understanding of these tumors.
RESULTS
PPTIDs, occupying an intermediate spectrum of malignancy, reveal diverse histological patterns, mitotic activity, and distinct methylation profiles. Surgical treatment is the gold standard, but when limited to partial removal, radiotherapy becomes crucial. While surgical approaches are standardized, due to the low prevalence of the pathology and absence of randomized prospective studies, there are no shared guidelines about radiation treatment modalities.
CONCLUSION
Surgical removal remains pivotal, demanding a personalized approach based on the tumor extension. This review underscores the considerable variability in treatment approaches and reported survival rates within the existing literature, emphasizing the need for ongoing research to better define optimal therapeutic strategies and prognostic factors for PPTIDs, aiming for further and more detailed stratification among them.
PubMed: 38592098
DOI: 10.3390/jcm13051266 -
Wiener Klinische Wochenschrift Apr 2024In view of the recent revival of interest in circadian biology and circadian epidemiology at the Medical University of Vienna, it seems appropriate to highlight the rich...
In view of the recent revival of interest in circadian biology and circadian epidemiology at the Medical University of Vienna, it seems appropriate to highlight the rich and pioneering history of circadian research in Austria. Among the forefathers of circadian research in Vienna are Otto Marburg (1874-1948), who discovered important elements of the pineal gland physiology, Robert Hofstätter (1883-1970), who used pineal gland extract in obstetrics/gynecology, and Paul Engel (1907-1997), who discovered that the pineal gland was controlled by light. More recently, Vera Lapin (1920-2007) showed that surgical removal of the pineal gland increased tumor growth, while Franz Waldhauser (*1946) investigated melatonin in conjunction with night work. Michael Kundi (*1950) and his team conducted among the first studies demonstrating differences in rhythms of night workers and early evidence for health impairments among them. Furthermore, Vienna-born Erhard Haus (1926-2013) pioneered the discovery of the role and importance of melatonin in relation to numerous diseases. This rich pioneering contribution of scientists in Vienna or with roots in Vienna is continued today by a new generation of chronobiologists, epidemiologists and clinicians in Vienna whose new insights contribute to the rapidly developing field of circadian rhythms research. Current topics and contributions relate to the impact of circadian rhythm disruption on health, and the application of chronotherapeutic approaches in clinical and preventive settings.
Topics: Pregnancy; Female; Humans; Melatonin; Austria; Circadian Rhythm; Pineal Gland
PubMed: 37256421
DOI: 10.1007/s00508-023-02199-z -
No Shinkei Geka. Neurological Surgery May 2024This article describes the concept and technical aspects of the occipital transtentorial approach(OTA)for tumor extraction in the pineal region, based on the author's... (Review)
Review
This article describes the concept and technical aspects of the occipital transtentorial approach(OTA)for tumor extraction in the pineal region, based on the author's experience and literature review. Awareness of the successful completion of each surgical step is essential. Preoperative preparation and imaging evaluations, with particular attention to the veins and venous sinuses, are especially important. It is also helpful to perform a complete dura incision and inversion up to the edge of confluence, superior sagittal sinus, and transverse sinus. Subsequently, it is necessary to understand the usefulness of adequate dissection in the vicinity of the corpus callosum and internal occipital vein(IOV)so that the occipital lobe can be moved without difficulty. Furthermore, development of the IOV with adequate tentoriotomy facilitates contralateral work. Finally, complete understanding of each step during the bilateral, ambient cistern and cerebellomesencephalic fissure dissection process, where the cerebellar vermis can be moved without difficulty, is necessary for a safe OTA to pineal region tumor extraction.
Topics: Humans; Neurosurgical Procedures; Pinealoma; Pineal Gland; Brain Neoplasms
PubMed: 38783507
DOI: 10.11477/mf.1436204958