Clinical Evaluation in Parkinson's Disease: Is the Golden Standard Shiny Enough?

Parkinson's disease (PD) has become the second most common neurodegenerative condition following Alzheimer's disease (AD), exhibiting high prevalence and incident rates. Current care strategies for PD patients include brief appointments, which are sparsely allocated, at outpatient clinics, where, in the best case scenario, expert neurologists evaluate disease progression using established rating scales and patient-reported questionnaires, which have interpretability issues and are subject to recall bias. In this context, artificial-intelligence-driven telehealth solutions, such as wearable devices, have the potential to improve patient care and support physicians to manage PD more effectively by monitoring patients in their familiar environment in an objective manner. In this study, we evaluate the validity of in-office clinical assessment using the MDS-UPDRS rating scale compared to home monitoring. Elaborating the results for 20 patients with Parkinson's disease, we observed moderate to strong correlations for most symptoms (bradykinesia, rest tremor, gait impairment, and freezing of gait), as well as for fluctuating conditions (dyskinesia and OFF). In addition, we identified for the first time the existence of an index capable of remotely measuring patients' quality of life. In summary, an in-office examination is only partially representative of most PD symptoms and cannot accurately capture daytime fluctuations and patients' quality of life.

Clinical features and diagnostic tools in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders affecting primarily muscles, but other organs can be involved. This review describes the clinical features, diagnosis and treatment for IIMs, namely polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and myositis associated with antisynthetase syndrome (ASS). The diagnostic approach has been updated recently based on the discovery of circulating autoantibodies, which has enhanced the management of patients. Currently, validated classification criteria for IIMs allow clinical studies with well-defined sets of patients but diagnostic criteria to guide the care of individual patients in routine clinical practice are still missing. This review analyzes the clinical manifestations and laboratory findings of IIMs, discusses the efficiency of modern and standard methods employed in their workup, and delineates optimal practice for clinical care. Α multidisciplinary diagnostic approach that combines clinical, neurologic and rheumatologic examination, evaluation of electrophysiologic and morphologic muscle characteristics, and assessment of autoantibody immunoassays has been determined to be the preferred approach for effective management of patients with suspected IIMs.

Vanillylmandelic acid protects against reperfusion injury in an experimental animal model of myocardial infarction.

Vanillylmandelic acid, a catecholamine end-metabolite, has been shown to have several biological properties in previous studies, despite considered biologically inactive. We examined the potential effects of vanillylmandelic acid on the ischemic heart following myocardial infarction and reperfusion on a rat model. Thirty-four female Wistar rats were randomized into two groups, control and experimental. They were anesthetized and subjected to myocardial infarction through left anterior descending artery ligation. A previously studied dose of vanillylmandelic acid (10 mg/kg) was administered and the following parameters were studied during ischemia and reperfusion: a) mortality b) severity of ventricular tachyarrhythmias c) premature ventricular contractions and d) heart rate. Administration of vanillymandelic acid significantly reduced the severity of ventricular tachyarrhythmias and mortality rate during reperfusion, while it did not affect any other of the parameters studied. In conclusion, reperfusion injury was blunted through vanillylmandelic acid administration, which seems to be mediated by parasympathetic activation.

Screening for prostate cancer: moving forward in the molecular era.

Prostate specific antigen (PSA) is the most widely known screening test to detect prostate cancer (PCa). However, PSA testing has been recently put under the microscope mainly due to its weak correlation with prostate malignancy. In several clinical trials the PSA-screening validity for the diagnosis of PCa was evaluated. PSA lacks the ability to define the progression potential of the disease usually resulting in overdiagnosis and overtreatment of patients. Therefore, the development of new "multivariate" prediction models for PCa that would combine the PSA screening marker (and probably PSA metrics) with better biomarkers and imaging techniques has become an evolving field. New screening tests and/or methods with increased specificity could reduce the number of men undergoing prostate biopsy - thus alleviating patients from the anxiety and the distress experienced by an unnecessary (negative) biopsy- and minimizes the healthcare cost. Herein, we reviewed the information on PSA and other novel tests that can assist in diagnosing clinically meaningful prostate cancer.

Correlation of bioelectrical impedance analysis phase angle with changes in oxidative stress on end-stage renal disease patients, before, during, and after dialysis.

Chronic kidney disease is a condition that promotes oxidative stress. There are conflicting evidence about the role of hemodialysis on oxidative stress, that are mostly related with the various types of membrane materials used, the quality and type of dialysate, the method used, etc. The phase angle (PhA), which is determined with bioelectrical impedance analysis (BIA), measures the functionality of cell membranes. In this study, the correlation of the PhA with parameters of oxidative stress is attempted for the first time. We evaluated parameters of oxidative status as total antioxidant capacity (TAC) in erythrocytes (RBCs) and plasma of patients with ESRD undergoing hemodialysis with low flux synthetic polysulfone membranes. Measurements were recorded from 30 patients (16 men and 14 women) aged 64 ± 14 years before, during, and after dialysis, and in 15 healthy volunteers aged 56 ± 12 years The PhA was obtained by BIA. The plasma TAC increased significantly (41%, p < 0.05). Intracellular TAC noted a non-significant increase. Total antioxidant capacity of the patients before and after hemodialysis was significantly lower from the healthy volunteers (p < 0.05) showing that ESRD patients are at the state of increased oxidative stress. The PhA increased in significantly positive correlation with plasma TAC at the end of hemodialysis. The process of hemodialysis with biocompatible synthetic membranes and bicarbonate dialysate improved plasma TAC. The positive correlation of PhA with extracellular TAC could evolve to a method of oxidative stress estimation by BIA but further research is needed.

Enhancement of the biological activity of hydroxytyrosol through its oxidation by laccase from Trametes versicolor.

The laccase-catalyzed oxidation of hydroxytyrosol (HT) towards the formation of its bioactive oligomer derivatives was investigated. The biocatalytic oligomerization was catalyzed by laccase from Trametes versicolor in aqueous or various water-miscible organic solvents and deep eutectic solvent (DES)-based media. Mass Spectroscopy and Nuclear Magnetic Resonance were used for the characterization of the products. The solvent system used significantly affects the degree of HT oligomerization. The use of 50 % v/v methanol favored the production of the HT dimer, while other organic solvents as well as DESs led to the formation of hydroxytyrosol trimer and other oligomers. In vitro studies showed that the HT dimer exhibits 3- to 4-fold enhanced antibacterial activity against Gram-positive and Gram-negative bacteria compared to the parent compound. Moreover, the ability of HT dimer to inhibit the activity of soybean lipoxygenase and Candida rugosa lipase was 1.5-fold higher than HT, while molecular docking supported these results. Furthermore, HT dimer showed reduced cytotoxicity against HEK293 cells and exhibited a strong ability to inhibit ROS formation. The enhanced bioactivity of HT dimer indicates that this compound could be considered for use in cosmetics, skin-care products, and nutraceuticals.

Carpal Tunnel Syndrome Automated Diagnosis: A Motor vs. Sensory Nerve Conduction-Based Approach.

The objective of this study was to evaluate the effectiveness of machine learning classification techniques applied to nerve conduction studies (NCS) of motor and sensory signals for the automatic diagnosis of carpal tunnel syndrome (CTS). Two methodologies were tested. In the first methodology, motor signals recorded from the patients' median nerve were transformed into time-frequency spectrograms using the short-time Fourier transform (STFT). These spectrograms were then used as input to a deep two-dimensional convolutional neural network (CONV2D) for classification into two categories: patients and controls. In the second methodology, sensory signals from the patients' median and ulnar nerves were subjected to multilevel wavelet decomposition (MWD), and statistical and non-statistical features were extracted from the decomposed signals. These features were utilized to train and test classifiers. The classification target was set to three categories: normal subjects (controls), patients with mild CTS, and patients with moderate to severe CTS based on conventional electrodiagnosis results. The results of the classification analysis demonstrated that both methodologies surpassed previous attempts at automatic CTS diagnosis. The classification models utilizing the motor signals transformed into time-frequency spectrograms exhibited excellent performance, with average accuracy of 94%. Similarly, the classifiers based on the sensory signals and the extracted features from multilevel wavelet decomposition showed significant accuracy in distinguishing between controls, patients with mild CTS, and patients with moderate to severe CTS, with accuracy of 97.1%. The findings highlight the efficacy of incorporating machine learning algorithms into the diagnostic processes of NCS, providing a valuable tool for clinicians in the diagnosis and management of neuropathies such as CTS.

Cell replacement therapy with stem cells in multiple sclerosis, a systematic review.

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.

Glioblastoma research on zebrafish xenograft models: a systematic review.

Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.

Graphene oxide and oxidized carbon nanodiscs as biomedical scaffolds for the targeted delivery of quercetin to cancer cells.

Targeting cancer cells without affecting normal cells poses a particular challenge. Nevertheless, the utilization of innovative nanomaterials in targeted cancer therapy has witnessed significant growth in recent years. In this study, we examined two layered carbon nanomaterials, graphene and carbon nanodiscs (CNDs), both of which possess extraordinary physicochemical and structural properties alongside their nano-scale dimensions, and explored their potential as nanocarriers for quercetin, a bioactive flavonoid known for its potent anticancer properties. Within both graphitic allotropes, oxidation results in heightened hydrophilicity and the incorporation of oxygen functionalities. These factors are of great significance for drug delivery purposes. The successful oxidation and interaction of quercetin with both graphene (GO) and CNDs (oxCNDs) have been confirmed through a range of characterization techniques, including FTIR, Raman, and XPS spectroscopy, as well as XRD and AFM. In vitro anticancer tests were conducted on both normal (NIH/3T3) and glioblastoma (U87) cells. The results revealed that the bonding of quercetin with GO and oxCNDs enhances its cytotoxic effect on cancer cells. GO-Quercetin and oxCNDs-Quercetin induced G0/G1 cell cycle arrest in U87 cells, whereas oxCNDs caused G2/M arrest, indicating a distinct mode of action. In long-term survival studies, cancer cells exhibited significantly lower viability than normal cells at all corresponding doses of GO-Quercetin and oxCNDs-Quercetin. This work leads us to conclude that the conjugation of quercetin to GO and oxCNDs shows promising potential for targeted anticancer activity. However, further research at the molecular level is necessary to substantiate our preliminary findings.

Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment.

In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research.

Firing Alterations of Neurons in Alzheimer's Disease: Are They Merely a Consequence of Pathogenesis or a Pivotal Component of Disease Progression?

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, yet its underlying causes remain elusive. The conventional perspective on disease pathogenesis attributes alterations in neuronal excitability to molecular changes resulting in synaptic dysfunction. Early hyperexcitability is succeeded by a progressive cessation of electrical activity in neurons, with amyloid beta (Aß) oligomers and tau protein hyperphosphorylation identified as the initial events leading to hyperactivity. In addition to these key proteins, voltage-gated sodium and potassium channels play a decisive role in the altered electrical properties of neurons in AD. Impaired synaptic function and reduced neuronal plasticity contribute to a vicious cycle, resulting in a reduction in the number of synapses and synaptic proteins, impacting their transportation inside the neuron. An understanding of these neurophysiological alterations, combined with abnormalities in the morphology of brain cells, emerges as a crucial avenue for new treatment investigations. This review aims to delve into the detailed exploration of electrical neuronal alterations observed in different AD models affecting single neurons and neuronal networks.

Stimulation of natural killer cells by homoeopathic complexes: an in vitro and in vivo pilot study in advanced cancer patients.

The present study was designed in order to evaluate the effects of five homoeopathic complex preparations on functional activity natural killer cells (NKCs) in advanced cancer patients. We examined the effects of Coenzyme Compositum®, Ubichinon Compositum®, Glyoxal Compositum®, Katalysatoren® and Traumeel® on the functional activity of NKCs. Experimental procedures included in vitro and in vivo trials. The in vitro trials were performed in NKCs isolated from 12 healthy volunteers (aged 44 ± 4 years) and incubated with the five homoeopathic complex preparations. The in vivo trials were performed in 15 advanced cancer patients (aged 55 ± 12 years) supplemented for 3 months with the homoeopathic preparations. All five homoeopathic preparations significantly increased the cytotoxic activity of the NKCs at the lowest NKCs/target cell ratio 12:1 (p < 0·05). The order of activity was: Ubichinon Compositum® > Glyoxal Compositum® > Katalysatoren® > Traumeel® > Coenzyme Compositum®. In the advanced cancer patients, the homoeopathic preparation significantly increased NKCs cytotoxic activity (p < 0·05). The homoeopathic complex preparations tested in this study can be used as an adjuvant immunotherapy in advanced cancer patients.

Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells.

Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 x 10(-3)M completely inhibited platelet aggregation (p < 0.05), decreased TXB2 levels (p < 0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p < 0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 +/- 34, 450 +/- 34 and 62 +/- 2.4% (p < 0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol.

Hydroxytyrosol produced by engineered Escherichia coli strains activates Nrf2/HO-1 pathway: An in vitro and in vivo study.

This study explores the biological effects of hydroxytyrosol (HT), produced by the metabolic engineering of Escherichia coli, in a series of in vitro and in vivo experiments. In particular, a metabolically engineered Escherichia coli strain capable of producing HT was constructed and utilized. HEK293 and HeLa cells were exposed to purified HT to determine non-toxic doses that can offer protection against oxidative stress (activation of Nrf2/HO-1 signaling pathway). Male CD-1 mice were orally supplemented with HT to evaluate (1) renal and hepatic toxicity, (2) endogenous system antioxidant response, and (3) activation of Nrf2/HO-1 system in the liver. HT protected cells from oxidative stress through the activation of Nrf2 regulatory network. Activation of Nrf2 signaling pathway was also observed in the hepatic tissue of the mice. HT supplementation was safe and produced differential effects on mice's endogenous antioxidant defense system. HT biosynthesized from genetically modified Escherichia coli strains is an alternative method to produce high-quality HT that exerts favorable effects in the regulation of the organism's response to oxidative stress. Nonetheless, further investigation of the multifactorial action of HT on the antioxidant network regulation is needed.

Does Green Exfoliation of Graphene Produce More Biocompatible Structures?

Graphene has been studied thoroughly for its use in biomedical applications over the last decades. A crucial factor for a material to be used in such applications is its biocompatibility. Various factors affect the biocompatibility and toxicity of graphene structures, including lateral size, number of layers, surface functionalization, and way of production. In this work, we tested that the green production of few-layer bio-graphene (bG) enhances its biocompatibility compared to chemical-graphene (cG). When tested against three different cell lines in terms of MTT assays, both materials proved to be well-tolerated at a wide range of doses. However, high doses of cG induce long-term toxicity and have a tendency for apoptosis. Neither bG nor cG induced ROS generation or cell cycle modifications. Finally, both materials affect the expression of inflammatory proteins such as Nrf2, NF-kB and HO-1 but further research is required for a safe result. In conclusion, although there is little to choose between bG and cG, bG's sustainable way of production makes it a much more attractive and promising candidate for biomedical applications.

Is graphene the rock upon which new era continuous glucose monitors could be built?

Diabetes mellitus' (DM) prevalence worldwide is estimated to be around 10% and is expected to rise over the next decades. Monitoring blood glucose levels aims to determine whether glucose targets are met to minimize the risk for the development of symptoms related to high or low blood sugar and avoid long-term diabetes complications. Continuous glucose monitoring (CGMs) systems emerged almost two decades ago and have revolutionized the way diabetes is managed. Especially in Type 1 DM, the combination of a CGM with an insulin pump (known as a closed-loop system or artificial pancreas) allows an autonomous regulation of patients' insulin with minimal intervention from the user. However, there is still an unmet need for high accuracy, precision and repeatability of CGMs. Graphene was isolated in 2004 and found immediately fertile ground in various biomedical applications and devices due to its unique combination of properties including its high electrical conductivity. In the last decade, various graphene family nanomaterials have been exploited for the development of enzymatic and non-enzymatic biosensors to determine glucose in biological fluids, such as blood, sweat, and so on. Although great progress has been achieved in the field, several issues need to be addressed for graphene sensors to become a predominant material in the new era of CGMs.

Oxidized-Multiwalled Carbon Nanotubes as Non-Toxic Nanocarriers for Hydroxytyrosol Delivery in Cells.

Carbon nanotubes (CNTs) possess excellent physicochemical and structural properties alongside their nano dimensions, constituting a medical platform for the delivery of different therapeutic molecules and drug systems. Hydroxytyrosol (HT) is a molecule with potent antioxidant properties that, however, is rapidly metabolized in the organism. HT immobilized on functionalized CNTs could improve its oral absorption and protect it against rapid degradation and elimination. This study investigated the effects of cellular oxidized multiwall carbon nanotubes (oxMWCNTs) as biocompatible carriers of HT. The oxidation of MWCNTs via H2SO4 and HNO3 has a double effect since it leads to increased hydrophilicity, while the introduced oxygen functionalities can contribute to the delivery of the drug. The in vitro effects of HT, oxMWCNTS, and oxMWCNTS functionalized with HT (oxMWCNTS_HT) were studied against two different cell lines (NIH/3T3 and Tg/Tg). We evaluated the toxicity (MTT and clonogenic assay), cell cycle arrest, and reactive oxygen species (ROS) formation. Both cell lines coped with oxMWCNTs even at high doses. oxMWCNTS_HT acted as pro-oxidants in Tg/Tg cells and as antioxidants in NIH/3T3 cells. These findings suggest that oxMWCNTs could evolve into a promising nanocarrier suitable for targeted drug delivery in the future.

Effect of Highly Hydrophilic Superparamagnetic Iron Oxide Nanoparticles on Macrophage Function and Survival.

Superparamagnetic iron oxide nanoparticles (SPIONs) have garnered significant attention in the medical sector due to their exceptional superparamagnetic properties and reliable tracking capabilities. In this study, we investigated the immunotoxicity of SPIONs with a modified surface to enhance hydrophilicity and prevent aggregate formation. The synthesized SPIONs exhibited a remarkably small size (~4 nm) and underwent surface modification using a novel "haircut" reaction strategy. Experiments were conducted in vitro using a human monocytic cell line (THP-1). SPIONs induced dose-dependent toxicity to THP-1 cells, potentially by generating ROS and initiating the apoptotic pathway in the cells. Concentrations up to 10 µg/mL did not affect the expression of Nrf2, HO-1, NF-κB, or TLR-4 proteins. The results of the present study demonstrated that highly hydrophilic SPIONs were highly toxic to immune cells; however, they did not activate pathways of inflammation and immune response. Further investigation into the mechanisms of cytotoxicity is warranted to develop a synthetic approach for producing effective, highly hydrophilic SPIONs with little to no side effects.

Cellular Localization of Orexin 1 Receptor in Human Hypothalamus and Morphological Analysis of Neurons Expressing the Receptor.

The orexin system is related to food behavior, energy balance, wakefulness and the reward system. It consists of the neuropeptides orexin A and B, and their receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). OX1R has selective affinity for orexin A, and is implicated in multiple functions, such as reward, emotions, and autonomic regulation. This study provides information about the OX1R distribution in human hypothalamus. The human hypothalamus, despite its small size, demonstrates a remarkable complexity in terms of cell populations and cellular morphology. Numerous studies have focused on various neurotransmitters and neuropeptides in the hypothalamus, both in animals and humans, however, there is limited experimental data on the morphological characteristics of neurons. The immunohistochemical analysis of the human hypothalamus revealed that OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The rest of the hypothalamic nuclei do not express the receptor, except for a very low number of neurons in the mammillary bodies. After identifying the nuclei and neuronal groups that were immunopositive for OX1R, a morphological and morphometric analysis of those neurons was conducted using the Golgi method. The analysis revealed that the neurons in the lateral hypothalamic area were uniform in terms of their morphological characteristics, often forming small groups of three to four neurons. A high proportion of neurons in this area (over 80%) expressed the OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results were analyzed, and shown to represent, at the cellular level, the distribution of OX1R, and we discuss the regulatory role of orexin A in the intra-hypothalamic areas, such as its special role in the plasticity of neurons, as well as in neuronal networks of the human hypothalamus.