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World Journal of Nuclear Medicine Jun 2024The biodistribution of gallium-68-dotatate (Ga-68-dotatate) and standardized uptake values (SUVs) using non-time-of-flight (TOF) positron emission...
The biodistribution of gallium-68-dotatate (Ga-68-dotatate) and standardized uptake values (SUVs) using non-time-of-flight (TOF) positron emission tomography/computed tomography (PET/CT) cameras is well established. However, with the eventual retirement of older PET cameras and their replacement with newer, highly sensitive TOF PET/CT cameras, where SUV measurements are reportedly higher, updated knowledge of normal SUV range is needed and, to our knowledge, not previously reported. Our objectives are as follows: To establish normal Ga-68-dotatate TOF SUV database for common structures and to aid the visual detection of abnormalities objectively. To compare SUV values using the TOF and non-TOF algorithms. Fifty consecutive patients referred routinely to our nuclear medicine service (20 men, 30 women; median age 55 years) with presumed neuroendocrine tumors underwent Ga-68-dotatate scans on a PET-CT camera having capability of reconstructing both TOF/non-TOF images. Region of interests (ROIs) were drawn around 24 normal structures as well as the primary lesion with abnormal radiotracer uptake and SUV was measured. The same ROI was analyzed using both algorithms simultaneously and both TOF and non-TOF SUV values were compared. Twelve hundred ROIs were evaluated. Non-TOF Ga-68-dotatate uptake in normal structures was in alignment with previously published studies. As compared to non-TOF, TOF images had better target to background ratios visually. TOF SUV was higher for all structures except for lung and brain. TOF SUV was more than double in adrenals/uncinate process of the pancreas; approximately 1.8 times in abnormal lesions, lymph nodes, pineal gland; and greater than 1.5 times in thyroid, breast, and pancreatic head. Normal database of Ga-68-dotatate TOF SUV is provided for common structures to aid visual detection of abnormalities objectively. Overall, TOF SUV measures higher in identical ROIs, with abnormal lesions measuring approximately 1.8 times higher versus non-TOF technology. These findings need to be taken in consideration when comparing patient scans imaged on different PET/CT technologies.
PubMed: 38933071
DOI: 10.1055/s-0044-1786529 -
Journal of Oral Biosciences Jun 2024Asthma is a common chronic inflammatory disease affecting more than 260 million people worldwide. Nocturnal exacerbations of asthma symptoms significantly affect sleep... (Review)
Review
BACKGROUND
Asthma is a common chronic inflammatory disease affecting more than 260 million people worldwide. Nocturnal exacerbations of asthma symptoms significantly affect sleep quality and contribute to the most serious asthma exacerbations, which can lead to respiratory failure or death. Although β-adrenoceptor agonists are the standard of care for asthma, their bronchodilatory effect for nocturnal asthma is limited, and medications that specifically target symptoms of nocturnal asthma are lacking.
HIGHLIGHT
Melatonin, which is secreted by the pineal gland, plays a crucial role in regulating circadian rhythms. Peak serum melatonin concentrations, which are inversely correlated with diurnal changes in pulmonary function, are higher in patients with nocturnal asthma than in healthy individuals. Melatonin potentiates bronchoconstriction through the melatonin MT receptor expressed in the smooth muscles of the airway and attenuates the bronchodilatory effects of β-adrenoceptor agonists, thereby exacerbating asthma symptoms. Melatonin inhibits mucus secretion and airway inflammation, potentially ameliorating asthma symptoms.
CONCLUSION
Melatonin may exacerbate or ameliorate various pathophysiological conditions associated with asthma. As a potential therapeutic agent for asthma, the balance between its detrimental effects on airway smooth muscles and its beneficial effects on mucus production and inflammation remains unclear. Further studies are needed to elucidate whether melatonin worsens or improves asthma symptoms.
PubMed: 38925352
DOI: 10.1016/j.job.2024.06.008 -
Histology and Histopathology Jun 2024The percentage of the total amount of melatonin produced in vertebrates that comes from the pineal is small (likely <5%) but, nevertheless, functionally highly... (Review)
Review
The percentage of the total amount of melatonin produced in vertebrates that comes from the pineal is small (likely <5%) but, nevertheless, functionally highly noteworthy. The significance of pineal melatonin is that it is secreted cyclically such that it has a critical function in influencing not only the suprachiasmatic nucleus but clock genes that reside in perhaps every cell throughout the organism. Extrapineal melatonin, which may be synthesized in the mitochondria of all other cells in much larger amounts than that in the pineal gland has a different function than that derived from the pineal gland. Its synthesis is not circadian and it is not directly impacted by the photoperiodic environment. Also, melatonin from the extrapineal sites is not normally secreted into the blood stream; rather, it acts locally in its cell of synthesis or, possibly via paracrine mechanisms, on immediately adjacent cells. The functions of extrapineal melatonin include central roles in maintaining molecular and redox homeostasis and actions in resisting pathological processes due to its ability to directly or indirectly detoxify free radicals. The vast majority of organisms that exist on Earth lack a pineal gland so pineal-derived melatonin is unique to vertebrates. Evidence suggests that all invertebrates, protists and plants synthesized melatonin and they have no pineal homolog; thus, the production of melatonin by extrapineal cells in vertebrates should not be unexpected. While the factors that control pineal melatonin synthesis are well documented, the processes that regulate extrapineal melatonin production are undefined.
PubMed: 38920277
DOI: 10.14670/HH-18-776 -
Drug Design, Development and Therapy 2024Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major... (Review)
Review
Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients' visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.
Topics: Melatonin; Humans; Diabetic Retinopathy; Macular Degeneration; Animals; Fundus Oculi; Antioxidants
PubMed: 38911030
DOI: 10.2147/DDDT.S471525 -
Nutrients May 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder identified by impairments in common social interactions and repetitive behaviors. In ASD patients,...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder identified by impairments in common social interactions and repetitive behaviors. In ASD patients, substantial morphological alterations have been observed in the hippocampus, which represents an important region for the development of social skills. Melatonin, commonly found in many foods and plants, is also produced by the pineal gland. This indolamine, known to regulate the circadian rhythm, shows antioxidant and anti-inflammatory properties. We therefore hypothesized that melatonin may reduce oxidative stress and inflammation in the hippocampus of ASD patients. We explored our hypothesis using the BTBR mouse, a well-regarded murine transgenic model for ASD. Immediately after weaning, male BTBR and C57BL/6 mice underwent an 8-week treatment with melatonin or vehicle. Later, through immunohistochemistry and the immunoblotting analysis of the hippocampus, we evaluated the overall expression and cellular localization of Nrf2 and SOD1, two enzymes involved in the oxidative stress response. Similarly, we evaluated NLRP3 and NFkB, two mediators of inflammation, and GAD67, an enzyme responsible for the synthesis of GABA. Ultimately, we addressed melatonin's potential to regulate iron metabolism through a DAB-enhanced Perls reaction assay. Results showed melatonin's potential for modulating the analyzed markers in BTBR mice, suggesting a potential neuroprotective effect in ASD patients.
Topics: Animals; Melatonin; Hippocampus; Male; Neuroprotective Agents; Mice; Mice, Inbred C57BL; Oxidative Stress; Disease Models, Animal; Autism Spectrum Disorder; Antioxidants; Mice, Transgenic; NF-E2-Related Factor 2; Inflammation
PubMed: 38892585
DOI: 10.3390/nu16111652 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Jun 2024Wound healing involves the repair of skin and other soft tissues after an injury. Royal jelly, a product of bees, possesses antioxidant, anti-inflammatory,... (Comparative Study)
Comparative Study
BACKGROUND
Wound healing involves the repair of skin and other soft tissues after an injury. Royal jelly, a product of bees, possesses antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Melatonin, a circadian indoleamine, is produced in the pineal gland and other organs. This study explores the effects of melatonin and royal jelly, both individually and combined, on wound healing in geriatric and young mice.
METHODS
The study includes 90 Balb/C mice divided into ten groups to assess the effects of royal jelly and melatonin on wound healing. Royal jelly was applied topically at a concentration of 300 mg/kg. Melatonin was formulated in a vaseline-based pomade at a concentration of 5 mg/kg. The substances were applied either separately or in combination to wounds created on the mice.
RESULTS
Both substances significantly enhanced wound healing at a macroscopic level in both age groups. Melatonin was found to be more effective during the initial wound formation process, whereas royal jelly was more beneficial during the granulation phase. However, significant results at a histopathological level were observed only in geriatric animals.
CONCLUSION
The findings suggest a potential new therapeutic approach to enhance wound healing, particularly in elderly individuals. However, these findings need to be supported through further research and clinical trials.
Topics: Animals; Melatonin; Wound Healing; Mice; Fatty Acids; Mice, Inbred BALB C; Male; Disease Models, Animal; Antioxidants; Wounds and Injuries
PubMed: 38863293
DOI: 10.14744/tjtes.2024.83307 -
Pharmacological Research Jul 2024Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates... (Review)
Review
Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.
Topics: Melatonin; Humans; Animals; Eye Diseases; Eye; Blood-Retinal Barrier
PubMed: 38862072
DOI: 10.1016/j.phrs.2024.107253 -
Developmental Biology Jun 2024The ways in which animals sense the world changes throughout development. For example, young of many species have limited visual capabilities, but still make social...
The ways in which animals sense the world changes throughout development. For example, young of many species have limited visual capabilities, but still make social decisions, likely based on information gathered through other sensory modalities. Poison frog tadpoles display complex social behaviors that have been suggested to rely on vision despite a century of research indicating tadpoles have poorly-developed visual systems relative to adults. Alternatively, other sensory modalities, such as the lateral line system, are functional at hatching in frogs and may guide social decisions while other sensory systems mature. Here, we examined development of the mechanosensory lateral line and visual systems in tadpoles of the mimic poison frog (Ranitomeya imitator) that use vibrational begging displays to stimulate egg feeding from their mothers. We found that tadpoles hatch with a fully developed lateral line system. While begging behavior increases with development, ablating the lateral line system inhibited begging in pre-metamorphic tadpoles, but not in metamorphic tadpoles. We also found that the increase in begging and decrease in reliance on the lateral line co-occurs with increased retinal neural activity and gene expression associated with eye development. Using the neural tracer neurobiotin, we found that axonal innervations from the eye to the brain proliferate during metamorphosis, with few retinotectal connections in recently-hatched tadpoles. We then tested visual function in a phototaxis assay and found tadpoles prefer darker environments. The strength of this preference increased with developmental stage, but eyes were not required for this behavior, possibly indicating a role for the pineal gland. Together, these data suggest that tadpoles rely on different sensory modalities for social interactions across development and that the development of sensory systems in socially complex poison frog tadpoles is similar to that of other frog species.
PubMed: 38851558
DOI: 10.1016/j.ydbio.2024.05.006 -
Sleep Medicine: X Dec 2024Melatonin, the primary hormone secreted by the pineal gland, regulates central and peripheral oscillators and adapts the internal environment to the external one through...
Melatonin, the primary hormone secreted by the pineal gland, regulates central and peripheral oscillators and adapts the internal environment to the external one through MT1 and MT2 receptors. The authors present a case of 16-year-old male intentionally overdosed on 900mg of melatonin (180 tablets) and 10 tablets of 0.5mg alprazolam. Admitted to the emergency department, he was extremely drowsy and minimally responsive with a Glasgow coma scale score of 8/15. Vital signs were stable, and no renal or liver dysfunction was noted. Elevated total leucocyte count and positive benzodiazepine urine test were observed. Gastric lavage was performed, and toxicology reports showed blood alprazolam levels at 0.15 mg/litre eight hours post-overdose. The patient regained consciousness 32 hours post-ingestion and was transferred to the psychiatry unit. This case underscores the increasing abuse of melatonin due to its easy availability and lack of regulation. Although melatonin has a low toxicity potential, side effects and interactions with other drugs can be severe. Supportive measures and vital sign control are crucial in overdose treatment.
PubMed: 38846909
DOI: 10.1016/j.sleepx.2024.100116 -
Physiological Research May 2024The Institute of Physiology of the Czech Academy of Sciences (CAS) has been involved in the field of chronobiology, i.e., in research on temporal regulation of...
From the Pineal Gland to the Central Clock in the Brain: Beginning of Studies of the Mammalian Biological Rhythms in the Institute of Physiology of the Czech Academy of Sciences.
The Institute of Physiology of the Czech Academy of Sciences (CAS) has been involved in the field of chronobiology, i.e., in research on temporal regulation of physiological processes, since 1970. The review describes the first 35 years of the research mostly on the effect of light and daylength, i.e., photoperiod, on entrainment or resetting of the pineal rhythm in melatonin production and of intrinsic rhythms in the central biological clock. This clock controls pineal and other circadian rhythms and is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. During the early chronobiological research, many original findings have been reported, e.g. on mechanisms of resetting of the pineal rhythm in melatonin production by short light pulses or by long exposures of animals to light at night, on modulation of the nocturnal melatonin production by the photoperiod or on the presence of high affinity melatonin binding sites in the SCN. The first evidence was given that the photoperiod modulates functional properties of the SCN and hence the SCN not only controls the daily programme of the organism but it may serve also as a calendar measuring the time of a year. During all the years, the chronobiological community has started to talk about "the Czech school of chronobiology". At present, the today´s Laboratory of Biological Rhythms of the Institute of Physiology CAS continues in the chronobiological research and the studies have been extended to the entire circadian timekeeping system in mammals with focus on its ontogenesis, entrainment mechanisms and circadian regulation of physiological functions. Key words: Pineal, Melatonin, AA-NAT rhythm, Light entrainment, Photoperiod, SCN clock.
PubMed: 38836462
DOI: No ID Found