The protective effect of Astaxanthin on scopolamine - induced Alzheimer's model in mice.

OBJECTIVES: To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine. METHODS: This research constituted an in vivo animal study encompassing 36 adult male mice, divided into 6 groups: Control, 100 mg/kg AST, 2 mg/kg scopolamine (AD group), 100 mg/kg AST+2 mg/kg scopolamine, 3 mg/kg galantamine+2 mg/kg scopolamine, and 100 mg/kg AST+3 mg/kg galantamine+2 mg/kg scopolamine. After 14 days, the mice's short-term memory, hippocampus tissue, oxidative and inflammatory markers were evaluated. RESULTS: The AST demonstrated a beneficial influence on short-term memory and a reduction in acetylcholinesterase activity in the brain. It exhibited neuroprotective and anti-amyloidogenic properties, significantly decreased pro-inflammatory markers and oxidative stress, and reversed the decline of the Akt-1 and phosphorylated Akt pathway, a crucial regulator of abnormal tau. Furthermore, AST enhanced the effect of galantamine in reducing inflammation and oxidative stress. CONCLUSION: The findings indicate that AST may offer therapeutic benefits against cognitive dysfunction in AD. This is attributed to its ability to reduce oxidative stress, control neuroinflammation, and enhance Akt-1 and pAkt levels, thereby underscoring its potential in AD treatment strategies.

Diagnostic utility of pediatric epilepsy monitoring unit: Retrospective single center study.

OBJECTIVE: To evaluate drug resistance epilepsy (DRE) patients with persistent seizures after using of standard antiepileptic drugs. This single center study aimed to investigate the utility of Epilepsy Monitoring Unit (EMU) resulted in a definitive diagnosis. METHODS: This was an observational retrospective study in 323 children who were admitted to the EMU for evaluation between 2012 and 2020. RESULTS: Of the 323 patients, 168 (52.01%) were males. The most common referral for EMU were better characterization 91 (28.17%) and pre-surgical evaluation 56 (17.3%). Of the participants, 273 (84.5%) had seizures one to 2 times per day. At discharge, 75.5% of admissions received a definitive diagnosis. CONCLUSION: The EMU admission for pediatric epilepsy patients is very important for early accurate diagnosis and management with surgery for those consider DRE patients.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Significant prostate cancer risk after MRI-guided biopsy showing benign findings: Results from a cohort of 381 men.

BACKGROUND: MRI-guided biopsy (MGB) contributes to the diagnosis of clinically significant Prostate Cancer (csPCa). However, there are no clear recommendations for the management of men after a negative MGB. The aim of this study was to assess the risk of csPCa after a first negative MGB. METHODS: Between 2014 and 2020, we selected men with a PI-RADS score ≥ 3 on MRI and a negative MGB (showing benign findings) performed for suspected prostate cancer. MGB (targeted and systematic biopsies) was performed using fully integrated mobile fusion imaging (KOELIS). The primary endpoint was the rate of csPCa (defined as an ISUP grade ≥ 2) diagnosed after a first negative MGB. RESULTS: A total of 381 men with a negative MGB and a median age of 65 (IQR: 59-69, range: 46-85) years were included. During the median follow-up of 31 months, 124 men (32.5%) had a new MRI, and 76 (19.9%) were referred for a new MGB, which revealed csPCa in 16 (4.2%) of them. We found no statistical difference in the characteristics of men diagnosed with csPCa compared with men with no csPCa after the second MGB. CONCLUSION: We observed a risk of significant prostate cancer in 4% of men two years after a negative MRI-guided biopsy. Performing a repeat MRI could improve the selection of men who will benefit from a repeat MRI-guided biopsy, but a clear protocol is needed to follow these patients.

Expression of Tie2 (angiopoietin receptor) on the monocyte subpopulations from ischemic stroke patients: Histological and flowcytometric studies.

INTRODUCTION: Different subpopulations of monocytes play roles in phagocytosis, inflammation, and angiogenic processes e.g., Tie2-expressing monocytes (TEMs). The brain is flooded with macrophages that are derived from monocytes within 3-7 days after a stroke. This study aimed to determine the expression level of Tie2 (an angiopoietin receptor) on monocytes and their subpopulations in ischemic stroke patients using the histological and immunohistological study of bone marrow biopsies and blood flow cytometry examination. METHODS: Ischemic stroke patients within two days were selected. Participants in the control group were healthy volunteers of matched age and gender. Sample collection was performed within 24 to 48 hours after medical consultants confirmed the stroke diagnosis. An iliac crest bone marrow biopsy was obtained and fixed for histological and immunohistological staining with antiCD14 and antiCD68. Flow cytometry was used to determine the total monocyte population, monocyte subpopulations, and TEMs after staining with monoclonal antibodies to CD45, CD14, CD16, and Tie2. RESULTS: Post-stroke patients' bone marrow cells were hypercellular. There was an apparent increase in CD68 and CD14-positive cells. Ischemic stroke patients exhibited low percentages of nonclassical monocytes CD14lowCD16++, with an increase in intermediate monocytes CD14highCD16+. Moreover, ischemic stroke patients had significantly higher levels of TEMs than control group. CONCLUSIONS: The results of this study demonstrate dysregulation of angiogenesis in monocyte subsets in ischemic stroke patients, which could be used as an early diagnostic marker of neurovascular damage and may need angiogenic therapy or improved medications to prevent further damage of blood vessels.

Application and performance of artificial intelligence technology in cytopathology.

Deep learning algorithms and artificial intelligence (AI) are making great progress in their capacity to evaluate and interpret image data recent advancements in computer vision and machine learning. The first use of AI in a pathology lab was in cytopathology, when a computer-assisted Pap test screening was created. Initially designed to diagnose rather than screen, there was a lot of disagreement concerning their wide use to clinical specimens. However, whole-slide imaging of both gynaecological and non-gynaecological histopathology have been the subject of recent AI work. An overview of the literature on AI in cytopathology is provided in this brief review. To be more precise, it intends to emphasize the relevance of applications of AI algorithms to gynaecological and non-gynaecologic cytology. Between January 2000 and December 2021, a search on artificial intelligence in cytopathology was conducted in several well-known databases, including PubMed, Web of Science, Scopus, Embase, and Google Scholar. Only full-text papers that could be accessed online were evaluated.

Neuroprotective Effect of Red Sea Marine Sponge Xestospongia testudinaria Extract Using In Vitro and In Vivo Diabetic Peripheral Neuropathy Models.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Oxidative stress plays an important role in the pathophysiology of DPN. Red Sea marine sponge Xestospongia testudinaria extract has a promising neuroprotective effect, presumably owing to its antioxidant and anti-inflammatory properties. Thus, this study aimed to investigate the neuroprotective effect of the sponge X. testudinaria extract on in vitro and in vivo models of DPN. Mice dorsal root ganglia (DRG) were cultured with high glucose (HG) media and used as an in vitro model of DPN. Some of the DRGs were pre-treated with 2 mg/mL of X. testudinaria. The X. testudinaria extract significantly improved the HG-induced decreased neuronal viability and the neurite length. It improved the oxidative stress biomarkers in DRG cultures. The DPN model was induced in vivo by an injection of streptozotocin at a dose of 150 mg/kg in mice. After 35 days, 0.75 mg/kg of the X. testudinaria extract improved the hot hyperalgesia and the DRG histology. Although the sponge extract did not reduce hyperglycemia, it ameliorated the oxidative stress markers and pro-inflammatory markers in the DRG. In conclusion, the current study demonstrates the neuroprotective effect of Red Sea sponge X. testudinaria extract against experimentally induced DPN through its antioxidant and anti-inflammatory mechanisms.

Secondary Cerebellar Cortex Injury in Albino Male Rats after MCAO: A Histological and Biochemical Study.

The present study focused on secondary injury following the middle cerebral artery (MCA) occlusion in rats not linked to the MCA's feeding zone. This entity has been very rarely studied. Additionally, this study investigated the rates of expression of five fundamental angiogenic biomarkers called endoglin, vascular endothelial growth factors-A (VEGF-A), endothelin-1 (ET-1), 2granulocyte colony-stimulating factor (G-CSF), and angiopoietin-using the MCA occlusion (MCAO) model. The random allocation of twelve adult male albino rats was in two groups. As a sham control group, six rats were used. This group was subjected to a sham operation without MCAO. The MCAO group consisted of six rats that were subjected to MCAO operation. After three days, the rats were sacrificed. The cerebellar specimens were immediately processed for light microscopic examination. An angiogenic biomarkers multiplex assay from multiplex was used to assess endoglin levels, VEGF-A, ET-1, angiopoietin-2, and G-CSF in serum samples. Hematoxylin and eosin-stained sections showed that the cerebellar cortex of rats of the MCAO group was more affected than the sham control group. Furthermore, Nissl stain and immunohistochemical analysis revealed an apparent increase in the number of positive immunoreactive in the cerebellar cortex and an evident decrease in Nissl granules in Purkinje cells of the MCAO rats, in contrast to the control rats. In addition, there was a significant increase in angiogenic factors VEGF-A, ET-1, angiopoietin-2, and endoglin. Interestingly, there was an increase in the G-CSF but a non-significant in the MCAO rats compared to the control rats. Furthermore, there was a significant correlation between the angiopoietin-2 and ET-1, and between G-CSF and ET-1. VEGF-A also exhibited significant positive correlations with the G-CSF serum level parameter, Endoglin, and ET-1. Rats subjected to MCAO are a suitable model to study secondary injury away from MCA's feeding zone. Additionally, valuable insights into the association and interaction between altered angiogenic factors and acute ischemic stroke induced by MCAO in rats.

Carvedilol Exerts Neuroprotective Effect on Rat Model of Diabetic Neuropathy.

Diabetic neuropathy (DN) commonly occurs in diabetics, affecting approximately 50% of both type 1 and 2 diabetic patients. It is a leading cause of non-traumatic amputations. Oxidative stress could play a key role in the pathophysiology of DN. This study aimed to investigate the potential neuroprotective effect of carvedilol on STZ-induced DN in rats. Thirty male Sprague Dawley rats (weighing 200-250 g) were randomly divided into five groups (six/group), where group 1 (negative control) received only the vehicle (0.5% of carboxymethyl cellulose orally 1 ml/kg). DN was induced by a single injection of remaining rats with streptozotocin (STZ; 50 mg/kg, i.p.). After diabetes induction, group 2 served as the diabetic untreated animals; while groups 3 and 4 were treated with carvedilol (1 and 10 mg/kg/d, orally, respectively). Group 5 received a-lipoic acid as a reference neuroprotective (100 mg/kg/d, orally). All treatments were continued for 45 days after diabetes induction, followed by behavioural tests. After sacrificing the animals, dorsal root ganglia, and sciatic nerves were collected for histopathological examination and biochemical assessments. Briefly, STZ administration caused cold allodynia, induced oxidative stress, and increased nerve growth factor (NGF) concentration. Nevertheless, carvedilol improved the behavioural tests, ameliorated the oxidative imbalance as manifested by reducing malondialdehyde, restoring glutathione content, and superoxide dismutase activity. Carvedilol also decreased NGF concentration in DRG homogenate. In conclusion, this study demonstrates the neuroprotective effect of carvedilol in an experimentally induced DN rat model through-at least partly-its antioxidant effect and reduced NGF concentration in DRG.

The combined effect of honey and olive oil against methotrexate mediated hepatotoxicity in rats: A biochemical, histological and immunohistological study.

BACKGROUND: Honey and olive oil are natural products that have high nutritional values, and therapeutic properties. Cytotoxic drugs, like methotrexate (MTX) are used to treat malignancies in tumour cells; however, these drugs also have serious side effects that could threaten the patient's life. AIM: To evaluate the potential protective effects of honey and olive oil, administered alone or together, against MTX-induced hepatotoxicity in rats. METHODS: Adult male albino rats were divided: Group I: negative control (n=8); II: honey ( daily by oral 1.2 g/kg bwt (n=8), III: olive oil (1 ml/day)(n=8), IV: single intraperitoneal injection of MTX (20 mg/kg bwt)(n=8), V: diluted honey for 3 days before injection of MTX (n=8), Group VI: olive oil for 3 days before injection of MTX (n=8), Group VII: both honey and olive oil for 3 days before injection of MTX (n=8). After treatment, rats were sacrified and blood samples were collected to determine liver function parameters, liver tissue used to measure the oxidative (malondialdehyde), antioxidative parameters (superoxide dismutase, catalase and glutathione peroxidase), histological and immunohistochemical techniques. RESULTS: The administration of honey and olive oil exerted a protective effect against MTX-induced hepatotoxicity, as demonstrated by the normalization of the liver enzymes, proteins and total bilirubin and by the histopathological and immunohistological changes observed in the livers. Both agents also reversed the oxidative damage in the liver by decreasing level of MDA levels and increasing the antioxidant related by enzymes in the liver homogenates compared to the control rats. These effects were more evident when the two agents were administered together. CONCLUSION: The combined intake of honey and olive oil could be hepatoprotective. Co-administration of these agents might form an effective adjuvant therapy and minimize side effects of chemoherapy in cancerous patients.

Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with Either Sporadic or Familial Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Mitochondrial abnormalities have been identified in many cell types in AD, with deficits preceding the development of the classical pathological aggregations. Ursodeoxycholic acid (UDCA), a treatment for primary biliary cirrhosis, improves mitochondrial function in fibroblasts derived from Parkinson's disease patients as well as several animal models of AD and Parkinson's disease. In this paper, we investigated both mitochondrial function and morphology in fibroblasts from patients with both sporadic and familial AD. We show that both sporadic AD (sAD) and PSEN1 fibroblasts share the same impairment of mitochondrial membrane potential and alterations in mitochondrial morphology. Mitochondrial respiration, however, was decreased in sAD fibroblasts and increased in PSEN1 fibroblasts. Morphological changes seen in AD fibroblasts include reduced mitochondrial number and increased mitochondrial clustering around the cell nucleus as well as an increased number of long mitochondria. We show here for the first time in AD patient tissue that treatment with UDCA increases mitochondrial membrane potential and respiration as well as reducing the amount of long mitochondria in AD fibroblasts. In addition, we show reductions in dynamin-related protein 1 (Drp1) level, particularly the amount localized to mitochondria in both sAD and familial patient fibroblasts. Drp1 protein amount and localization were increased after UDCA treatment. The restorative effects of UDCA are abolished when Drp1 is knocked down. This paper highlights the potential use of UDCA as a treatment for neurodegenerative disease.

Current developments in gene therapy for amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating adult neurodegenerative disorder characterized by motor neuron degeneration and death around 3 years from onset. So far, riluzole is the only treatment available, although it only offers a slight increase in survival. The complex etiology of ALS, with several genes able to trigger the disease, makes its study difficult. AREAS COVERED: RNA-mediated or protein-mediated toxic gain-of-function leading to motor neuron degeneration appears to be likely common pathogenic mechanisms in ALS. Consequently, gene therapy technologies to reduce toxic RNA and/or proteins and to protect motor neurons by modulating gene expression are at the forefront of the field. Here, we review the most promising scientific advances, paying special attention to the successful treatments tested in animal models as well as analyzing relevant gene therapy clinical trials. EXPERT OPINION: Despite broad advances in target gene identification in ALS and advances in gene therapy technologies, a successful gene therapy for ALS continues to elude researchers. Multiple hurdles encompassing technical, biological, economical and clinical challenges must be overcome before a therapy for patients becomes available. Optimism remains due to positive results obtained in several in vivo studies demonstrating significant disease amelioration in animal models of ALS.

Inhibition of plasminogen activation by polymerized ampicillin.

The polymerized beta-lactam antibiotic ampicillin inhibits the proteolytic activity of human plasmin upon 125I-labeled fibrin clots. The inhibition is dose-dependent, with half-maximal inhibition occurring at 1.25 mM of the polymerized antibiotic. Polymerized ampicillin also inhibits binding of plasmin to fibrin, and 38% inhibition of binding occurs at 10 mM of the antibiotic. Furthermore, polymerized ampicillin inhibits the activation of plasminogen by either urokinase-like plasminogen activator (uPA) or tissue type-plasminogen activator (tPA). At 7.5 mM of polymerized ampicillin, the uPA-mediated plasminogen activation is suppressed by 94%, and half-maximal inhibition is obtained at 0.66 mM. The direct activity of uPA on the chromogenic substrate L-pyroglutamyl-glycyl-L-arginine p-nitroanilide hydrochloride (S-2444) is unaffected by polymerized ampicillin levels of up to 10 mM. The inhibitory effects of the polymerized antibiotic on the activation of plasminogen by both uPA and tPA is totally abolished in presence of fibrin. These interactions may serve as a novel model for ligands that enhance the clot-specificity of thrombolytic agents.

Is camptocormia a primary muscular disease?

STUDY DESIGN: This study analyzed computed tomographic scans, magnetic resonance images, and biopsies of the paravertebral muscles of patients with camptocormia and age-matched patients with lumbar interapophyseal osteoarthritis or lumbar vertebral stenosis. OBJECTIVES: To define the muscular lesions and clarify their nature in this particular disorder. SUMMARY OF BACKGROUND DATA: Progressive lumbar kyphosis or camptocormia, a rare disease of the elderly characterized by inability to immobilize the lumbar spine in relation to the pelvis appears to be a result of weakness of the paraspinal muscles. The features presented by these patients do not correspond to any myopathy previously described. METHODS: Twenty-seven patients (5 men and 22 women) mean age 69 years, with camptocormia were compared to fifteen age-matched patients without camptocormia but with posterior interapophyseal osteoarthritis and to nine elderly patients operated for narrowing of lumbar canal. Computed tomographic scans, magnetic resonance images, light microscopy, histochemistry, and electron microscopy of paraspinal muscles were obtained in both groups. RESULTS: In patients with camptocormia, computed tomographic scans and magnetic resonance imaging showed heterogeneous appearance of the spinal muscles with areas of low density. These features were distinct from those of patients with interapophyseal osteoarthritis and were similar to the features described in primary muscular dystrophies. The main microscopic change in camptocormia was the increase of fibrous tissue, frequently with a lobular pattern, not seen in osteoarthritic patients. Familial history of the disorder was frequent (20 out of the 27 patients). CONCLUSION: Camptocormia, disappearing in the recumbent position, is thus very probably linked to muscle involvement. That there is often a family history of such disorder is in favor of a genetically transmitted condition. Magnetic resonance images and computed tomographic scan appearance seems to be in favor of primary muscular disease, restricted to the spinal muscles.

The one-stage preauricular flap for male pattern baldness: long-term results and risk factors.

Following a review of the operative technique for a single-stage vertical flap for reconstruction of the frontal hairline, we present a series of 156 such flaps with a minimum follow-up of 6 months. Risk factors for necrosis or alopecia of the distal end of the flap include retroauricular design and cigarette smoking. There was not a single case of necrosis in nonsmokers with flaps shorter than 16 cm. Finally, we demonstrate that the final appearance of the donor site is directly related to the tension under which it is closed.

[Assessing the quality of patients' medical records at the Claudius-Regaud Institute]. / Evaluation de la qualité du dossier du patient a l'institut Claudius-Regaud.

In 1999, the Claudius-Regaud Institute of Toulouse, France, specialized in oncology, set up a workshop in order to assess the quality of its patients medical records. A retrospective evaluation was performed on a 100-chart-sample drawn from all the charts in the institution. Results show that the medical records are subdivised into three parts: medical care, nursing care and imaging. Some of the explored charts show a lack of data, and a certain inconsistency in the charts' organization and in the structure of information was reported. Patient's record is a key to communication between the different care providers in oncology. To improve its quality, efforts will have to be done in restructuring the charts, creating guidelines and training the different caregivers.

[Postpneumonectomy thoracic empyema and dosimetric CT scan. Report of two cases and review of the literature]. / Empyème thoracique postpneumonectomie et scanographie dosimétrique. A propos de deux observations et revue de la littérature.

Following a pneumonectomy for cancer, the patients are classically observed by clinical examination and standard chest X-ray. However, torpid empyemas can be missed when they occur after the period of hospitalization and when they are not accompanied by a fever. At the time of postoperative radiotherapy, the dosimetric CT scan constitutes the first examination providing objective information of the endothoracic content. It is therefore necessary on this occasion to assure the normality of the postpneumonectomy pleural space while checking that the substituted liquid is homogeneous and above all that the internal mediastinal part of the cavity has a concave appearance. If that is not the case, an empyema should be suspected. The diagnosis, confirmed by a cytobacteriological examination of the pleural fluid, constitutes a counterindication of the radiotherapy. We present two cases of postpneumonectomy paucisymptomatic empyema which were diagnosed during the course of postoperative radiotherapy when the initial dosimetric CT scan was pathologic and could have allowed an earlier diagnosis.

[Primary dural lymphoma: a report of two cases with review of the literature]. / Lymphome dural primitif: à propos de deux cas et revue de la littérature.

Primary lymphoma arising in dura is exceedingly rare. We report the clinicopathologic findings of two patients with primary B-cell lymphoma of dura. Both were female, 38 and 45 years old. Prior to biopsy they were felt to have meningioma on preoperative magnetic resonance imagery. Histologically, tumors were classified as MALT-type lymphoma. Literature describe only 14 reports of similar entity. Primary lymphomas arising in dura appear to have a more favourable clinical course compared to PCNSL and may require a less aggressive treatment.

[Systemic granulomatosis caused by a Dacron prosthetic ligament]. / Granulomatose systémique induite par un ligament prothétique en Dacron.

An uncommon systemic reaction mimicking sarcoidosis after ligament reconstruction is reported. Clinical and radiological outcome after surgical treatment led to the diagnosis of a a specific injury caused by the ligament reconstruction device.