Nakashima M, Suga N, Fukumoto A
… +2 more, Yoshikawa S, Matsuda S
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39850247
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Metabolic syndrome is a group of pathological disorders increasing the risk of serious diseases including cardiovascular disease, stroke, type 2 diabetes. Global widespread of the metabolic syndrome has put a heavy socia...Metabolic syndrome is a group of pathological disorders increasing the risk of serious diseases including cardiovascular disease, stroke, type 2 diabetes. Global widespread of the metabolic syndrome has put a heavy social burden. Interestingly, a crucial link between the metabolic syndrome and a psychiatric disorder may frequently coexist, in which certain shared mechanisms might play a role for the pathogenesis. In fact, some microRNAs (miRNAs) have been detected in the overlap pathology, suggesting a common molecular mechanism for the development of both disorders. Subsequent studies have revealed that these miRNAs and several metabolites of gut microbiota such as short chain fatty acids (SCFAs) might be involved in the development of both disorders, in which the association between gut and brain might play key roles with engram memory for the modulation of immune cells. Additionally, the correlation between brain and immunity might also influence the development of several diseases/disorders including metabolic syndrome. Brain could possess several inflammatory responses as an information of pathological images termed engrams. In other words, preservation of the engram memory might be achieved by a meta-plasticity mechanism that shapes the alteration of neuron linkages for the development of immune-related diseases. Therefore, it might be rational that metabolic syndrome and psychiatric disorders may belong to a group of immune-related diseases. Disrupting in gut microbiota may threaten the body homeostasis, leading to initiate a cascade of health problems. This concept may contribute to the development of superior therapeutic application with the usage of some functional components in food against metabolic and psychiatric disorders. This paper reviews advances in understanding the regulatory mechanisms of miRNAs with the impact to gut, liver and brain, deliberating the probable therapeutic techniques against these disorders.
Chidebe EO, Moke EG, Asiwe JN
… +8 more, Ben-Azu B, Demaki WE, Oritsemuelebi B, Arighwrode O, Avabore AN, Omogbiya AI, Eduviere AT, Umukoro EK
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39850246
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OBJECTIVES: The significant correlation between acute myocardial infarction and subsequent hepatorenal dysfunction could result in a higher mortality rate in patients. The study aimed to evaluate the effect and mechanism...OBJECTIVES: The significant correlation between acute myocardial infarction and subsequent hepatorenal dysfunction could result in a higher mortality rate in patients. The study aimed to evaluate the effect and mechanisms of coenzyme-Q10 (Q10) administration on hepatorenal dysfunction in an isoprenaline (ISO)-induced myocardial infarction model in rats. MATERIALS AND METHODS: Twenty male rats were assigned into four groups (n = 5). Groups 1-2 were administered intraperitoneally with normal saline, groups 3-4 were pretreated with Q10 (10 mg/kg, i.p.) for 28 days, and groups 2 and 4 received ISO (200 mg/kg, i.p.) on the last two days. Body, kidney, and liver weights, antioxidants and biochemical biomarkers, and histopathological investigation of the liver and kidney tissues were performed. RESULTS: The administration of ISO significantly (P < 0.05) increased oxidative stress and altered the liver and renal function integrity and morphology. Pretreatment with Q10 demonstrated a protective effect against biochemical and histological alterations through significantly enhanced antioxidant actions, notably increasing the levels of superoxide dismutase, catalase, glutathione, and glutathione transferase; reduced liver enzymes (aspartate transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase), decreased urea and creatinine concentrations and reduced the gravity of histomorphological changes in hepatic and renal tissues of ISO treated rats. CONCLUSION: Overall, our result suggests that Q10 confers hepatic and renal protection against ISO-induced hepatorenal dysfunction accompanying myocardial infarction through its antioxidant effects and amelioration of fibrotic changes.
Shriya S, Paul R, Singh N
… +2 more, Afza F, Jain BP
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39850245
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OBJECTIVE: The Heat Shock Protein 70 (HSP70) family is a highly conserved group of molecular chaperones essential for maintaining cellular homeostasis. These proteins are necessary for protein folding, assembly, and degr...OBJECTIVE: The Heat Shock Protein 70 (HSP70) family is a highly conserved group of molecular chaperones essential for maintaining cellular homeostasis. These proteins are necessary for protein folding, assembly, and degradation and involve cell recovery from stress conditions. HSP70 proteins are upregulated in response to heat shock, oxidative stress, and pathogenic infections. Their primary role is preventing protein aggregation, refolding misfolded proteins, and targeted degradation of irreparably damaged proteins. Given their involvement in fundamental cellular processes and stress responses, HSP70 proteins are critical for cell survival and modulating disease outcomes in cancer, neurodegeneration, and other pathologies. The present study aims to understand domain architecture, physicochemical properties, phosphorylation, ubiquitination, and alternative polyadenylation site prediction in various HSP70 members. METHOD: SMART and InterProScan software were used for domain analysis. EXPASY Protparam, NetPhos 3.1 server DTU, and MUbisiDa were used for physicochemical analysis, phosphorylation, and ubiquitination site analysis, respectively. Alternative polyadenylation was studied using the EST database. RESULT: Domain analysis shows that coiled-coil and nucleotide-binding domains are present in some of the HSP70 members. Five HSP70 family members have alternate polyadenylation sites in their 3'UTR. CONCLUSION: The present work has provided valuable insights into their structure, functions, interactome, and polyadenylation patterns. Studying their therapeutic potential in diseases like cancer can be helpful.
Nakashima M, Suga N, Fukumoto A
… +2 more, Yoshikawa S, Matsuda S
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39583750
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Alzheimer's disease is the most general type of cognitive impairments. Until recently, strategies that prevent its clinical progression have remained more elusive. Consequently, research direction should be for finding e...Alzheimer's disease is the most general type of cognitive impairments. Until recently, strategies that prevent its clinical progression have remained more elusive. Consequently, research direction should be for finding effective neuroprotective agents. It has been suggested oxidative stress, mitochondrial injury, and inflammation level might lead to brain cell death in many neurological disorders. Therefore, several autophagy-targeted bioactive compounds may be promising candidate therapeutics for the prevention of brain cell damage. Interestingly, some risk genes to Alzheimer's disease are expressed within brain cells, which may be linked to cholesterol metabolism, lipid transport, endocytosis, exocytosis and/or caveolae formation, suggesting that caveolae may be a fruitful therapeutic target to improve cognitive impairments. This review would highlight the latest advances in therapeutic technologies to improve the treatment of Alzheimer's disease. In particular, a paradigm that serotonin and N-methyl-d-aspartate (NMDA) receptors agonist/antagonist within caveolae structure might possibly improve the cognitive impairment. Consequently, cellular membrane biophysics should improve our understanding of the pathology of the cognitive dysfunction associated with Alzheimer's disease. Here, this research direction for the purpose of therapy may open the potential to move a clinical care toward disease-modifying treatment strategies with certain benefits for patients.
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39310738
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Extracellular vesicles (EVs) have emerged as a fascinating area of research in molecular biology, with diverse therapeutic applications. These small membrane-bound structures, released by cells into the extracellular spa...Extracellular vesicles (EVs) have emerged as a fascinating area of research in molecular biology, with diverse therapeutic applications. These small membrane-bound structures, released by cells into the extracellular space, play a crucial role in intercellular communication and hold great potential for advancing medical treatments. The aim of this study is to have a narrative review on the use and therapeutic applications of EVs. Their unique characteristics, including stability, biocompatibility, and the ability to traverse biological barriers, make them promising tools for targeted drug delivery. By engineering EVs to encapsulate specific cargo molecules, such as therapeutic proteins, small interfering RNA (siRNA), or anti-cancer drugs, researchers can enhance drug stability and improve targeted delivery to desired cells or tissues. This approach can minimize off-target effects and improve therapeutic efficacy. Based on our literature search, we found that EVs can be used as biomarkers to predict diseases. Although much progress has been made in understanding the biology and function of exosomes, there are still unanswered questions that require further research. This includes identifying appropriate and safe techniques for producing exosomes in large quantities, determining which types of cells are suitable for exosome donor cells for therapeutic purposes, and investigating the safety of exosomes in human studies. Overall, the use of exosomes in clinical therapeutic applications requires a strong understanding of molecular signaling cascades and exosome profiles, as well as the specificity and sensitivity of biomarker and drug delivery methods.
Riahi F, Kiani P, Golabbakhsh A
… +8 more, Khanezarrin M, Abbaspour M, Dormiani Tabatabaei SA, Fesharaki S, Tooyserkani SH, Bakhshi R, Azizollahi S, Mohammadi H
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39310737
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BACKGROUND: PET/CT and PET/MRI are two useful imaging modalities in neuro-oncology. Our aim was to review the existing literature on the benefits and drawbacks of using PET/CT and PET/MRI in the diagnosis of central nerv...BACKGROUND: PET/CT and PET/MRI are two useful imaging modalities in neuro-oncology. Our aim was to review the existing literature on the benefits and drawbacks of using PET/CT and PET/MRI in the diagnosis of central nervous system (CNS) tumors. METHODS: A literature search was conducted using valid databases, limited to English-language articles published between 2010 and 2023, and independently reviewed by two reviewers. A standard data extraction form was used to extract data from the included papers. The results were condensed and narratively presented, accompanied by supporting data from the included investigations. RESULTS: The study analyzed 28 articles, mostly from Europe. The results varied, with some studies comparing PET/CT and PET/MRI, examining specific types of brain tumors, pediatric tumors, or focusing on specific PET/CT or PET/MRI modalities. The synthesis aimed to provide a comprehensive overview of PET/CT and PET/MRI use in CNS malignancies. CONCLUSIONS: PET/MRI offers promising advantages in neuro-oncology diagnosis and follow-up imaging, but its use should be prioritized in appropriate situations.
Silwal P, Singhal P, Senecal JM
… +3 more, Senecal JE, Lynn BD, Nagy JI
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39021417
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BACKGROUND: Sexually dimorphic spinal motoneurons (MNs) in the dorsomedial nucleus (DMN) and dorsolateral nucleus (DLN) as well as those in the cremaster nucleus are involved in reproductive behaviours, and the cremaster...BACKGROUND: Sexually dimorphic spinal motoneurons (MNs) in the dorsomedial nucleus (DMN) and dorsolateral nucleus (DLN) as well as those in the cremaster nucleus are involved in reproductive behaviours, and the cremaster nucleus additionally contributes to testicular thermoregulation. It has been reported that MNs in DMN and DLN are extensively linked by gap junctions forming electrical synapses composed of connexin36 (Cx36) and there is evidence that subpopulation of MNs in the cremaster nucleus are also electrically coupled by these synapses. METHODOLOGY: We used immunofluorescence methods to detect enhanced green fluorescent protein (eGFP) reporter for Cx36 expression in these motor nuclei. RESULTS: We document in male mice that about half the MNs in each of DMN and DLN express eGFP, while the remaining half do not. Further, we found that the eGFP vs. eGFP subsets of MNs in each of these motor nuclei innervate different target muscles; eGFP MNs in DMN and DLN project to sexually dimorphic bulbocavernosus and ischiocavernosus muscles, while the eGFP subsets project to sexually non-dimorphic anal and external urethral sphincter muscles. Similarly, eGFP vs. eGFP cremaster MNs were found to project to anatomically distinct portions of the cremaster muscle. By immunofluorescence, nearly all motoneurons in both DMN and DLN displayed punctate labelling for Cx36, including at eGFP/eGFP, eGFP/eGFP and eGFP/eGFP cell appositions. CONCLUSIONS: Most if not all motoneurons in DMN and DLN are electrically coupled, including sexually dimorphic and non-dimorphic motoneurons with each other, despite absence of eGFP reporter in the non-dimorphic populations in these nuclei that have selective projections to sexually non-dimorphic target muscles.
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39021416
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The everyday clinical practice of anesthesia has been transformed by the new reversal agent Sugammadex. With multiple benefits to this agent, including immediate reversibility of certain neuromuscular blocking agents, a...The everyday clinical practice of anesthesia has been transformed by the new reversal agent Sugammadex. With multiple benefits to this agent, including immediate reversibility of certain neuromuscular blocking agents, a more robust reversal, and the ability to keep a deeper plane of paralysis throughout surgical procedures, this medication has provided anesthesiologists with a new and improved ability to provide high quality care to their patients. The effectiveness of the reversal provided by this agent has also improved the incidence of post-operative complications relating to improper reversal and the need for reintubations. With the new American Society of Anesthesiologists (ASA) guidelines on neuromuscular blockade and its reversal, Sugammadex has been easily and quickly adopted into everyday clinical practice.
Thomas D, Recabal-Beyer A, Senecal JM
… +4 more, Serletis D, Lynn BD, Jackson MF, Nagy JI
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 39021415
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BACKGROUND: Granule cells in the hippocampus project axons to hippocampal CA3 pyramidal cells where they form large mossy fiber terminals. We have reported that these terminals contain the gap junction protein connexin36...BACKGROUND: Granule cells in the hippocampus project axons to hippocampal CA3 pyramidal cells where they form large mossy fiber terminals. We have reported that these terminals contain the gap junction protein connexin36 (Cx36) specifically in the stratum lucidum of rat ventral hippocampus, thus creating morphologically mixed synapses that have the potential for dual chemical/electrical transmission. METHODOLOGY: Here, we used various approaches to characterize molecular and electrophysiological relationships between the Cx36-containing gap junctions at mossy fiber terminals and their postsynaptic elements and to examine molecular relationships at mixed synapses in the brainstem. RESULTS: In rat and human ventral hippocampus, many of these terminals, identified by their selective expression of vesicular zinc transporter-3 (ZnT3), displayed multiple, immunofluorescent Cx36-puncta representing gap junctions, which were absent at mossy fiber terminals in the dorsal hippocampus. In rat, these were found in close proximity to the protein constituents of adherens junctions (i.e., N-cadherin and nectin-1) that are structural hallmarks of mossy fiber terminals, linking these terminals to the dendritic shafts of CA3 pyramidal cells, thus indicating the loci of gap junctions at these contacts. Cx36-puncta were also associated with adherens junctions at mixed synapses in the brainstem, supporting emerging views of the structural organization of the adherens junction-neuronal gap junction complex. Electrophysiologically induced long-term potentiation (LTP) of field responses evoked by mossy fiber stimulation was greater in the ventral than dorsal hippocampus. CONCLUSIONS: The electrical component of transmission at mossy fiber terminals may contribute to enhanced LTP responses in the ventral hippocampus.
Alevrakis E, Papadakis DD, Vagionas D
… +4 more, Koutsoukou A, Pontikis K, Rovina N, Vasileiadis I
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 38765808
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INTRODUCTION: Metabolic acidosis is very common amongst critically ill sepsis patients partly due to the presence of unmeasured ions in serum. These ions can be detected by anion gap (AG) or strong ion gap (SIG) concentr...INTRODUCTION: Metabolic acidosis is very common amongst critically ill sepsis patients partly due to the presence of unmeasured ions in serum. These ions can be detected by anion gap (AG) or strong ion gap (SIG) concentration values. The purpose of this study is to assess the correlation and potential agreement of the two methods in critically ill patients with sepsis. MATERIALS AND METHODS: The present is a retrospective study including septic patients admitted to the Intensive Care Unit from December 2014 to July 2016. The [SIG] and the [AG] corrected for albumin and lactate ([AG]) were calculated on admission and on sepsis remission or deterioration. The correlation of the two parameters was assessed in all patient groups using the Pearson correlation coefficient and linear regression analysis and the agreement with Bland-Altman plots. ROC survival curves were also generated for the patients in relation to the values of [AG], [SIG] and inorganic [SIG] ([SIG]) on admission. RESULTS: There was a strong correlation linking [AG] and [SIG] values (r>0.9, P<0.05) in all patient groups. The results from all three linear regression equations were statistically significant as the models predicted the [AG] value from the [SIG] value with high accuracy. The mean difference of the two methods (i.e. [AG] - [SIG] in every patient separately) in septic patients on admission was 11.75 mEq/l with 95% limits of agreement [9.7-13.8]; in patients with sepsis deterioration, it was 11.8 mEq/l with 95% limits of agreement [9.8-13.7] and in patients with sepsis remission, it was 11.5 mEq/l with 95% limits of agreement [10.4-12.7]. ROC survival curves demonstrated a small area under the curve (AUC): [SIG] AUC: 0.479, 95% CI [0.351, 0.606], [SIG] AUC: 0.581, 95% CI [0.457, 0.705], [AG] AUC: 0.529, 95% CI [0.401, 0.656]. CONCLUSION: [AG] and [SIG] demonstrate excellent correlation in septic patients, with a mean difference of about 12 mEq/l. Both parameters failed to demonstrate any predictive ability regarding patient mortality.
Int J Physiol Pathophysiol Pharmacol
· 2024 · PMID 38618492
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Extracellular vesicles (EVs) have emerged as a captivating field of study in molecular biology with diverse applications in therapeutics. These small membrane-bound structures, released by cells into the extracellular sp...Extracellular vesicles (EVs) have emerged as a captivating field of study in molecular biology with diverse applications in therapeutics. These small membrane-bound structures, released by cells into the extracellular space, play a vital role in intercellular communication and hold immense potential for advancing medical treatments. EVs, including exosomes, microvesicles, and apoptotic bodies, are classified based on size and biogenesis pathways, with exosomes being the most extensively studied. The aim of this study was to examine the molecular secretory pathway of exosomes and to discuss the medical applications of exosomes and the methods for employing them in laboratory models. The therapeutic potential of EVs has garnered significant attention. Their unique properties, such as stability, biocompatibility, and capacity to traverse biological barriers, make them promising vehicles for targeted drug delivery. By engineering EVs to carry specific cargo molecules, such as therapeutic proteins, small interfering Ribonucleic Acid (RNAs) (siRNAs), or anti-cancer drugs, researchers can enhance drug stability and improve their targeted delivery to specific cells or tissues. This approach has the potential to minimize off-target effects and increase therapeutic efficacy, offering a more precise and effective treatment strategy. EVs represent a captivating and rapidly evolving field with significant therapeutic implications. Their role in intercellular communication, targeted drug delivery, and regenerative medicine makes them valuable tools for advancing medical treatments. As our understanding of EV biology and their therapeutic applications continues to expand, we can expect remarkable advancements that will revolutionize the field of medicine and lead to more personalized and effective therapies.
Jamalipour Soufi G, Hekmatnia A, Hekmatnia F
… +4 more, Zarei AP, Bahrami M, Rasti S, Riahi F
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 38213796
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BACKGROUND: Patellofemoral osteoarthritis (PFOA) is a common cause of knee discomfort and impairment, particularly among athletes. The development of PFOA has been associated with anatomical knee variations, such as troc...BACKGROUND: Patellofemoral osteoarthritis (PFOA) is a common cause of knee discomfort and impairment, particularly among athletes. The development of PFOA has been associated with anatomical knee variations, such as trochlear dysplasia and patella alta. However, the relationship between these anatomical variants and the development of PFOA remains poorly understood. This study aimed to investigate the association between PFOA and knee anatomical variants in a cohort of patients. METHODS: The study included 200 patients with PFOA and 200 healthy controls. In this study, we investigate the relationship of osteoarthritis with both anatomical variants and demographic characteristics. The participants underwent Magnetic resonance imaging (MRI) evaluation of the knee, and anatomical variants including trochlear dysplasia and patella alta were assessed. The severity of PFOA was also graded based on cartilage area and depth, as well as the bone marrow involvement and presence of osteophytes. RESULTS: Statistically significant differences were observed between the two groups in terms of Tibial tuberosity-trochlear groove (TT-TG) distance, patella position, trochlear dysplasia, and Insall-Salvati ratio. The mean TT-TG distance, prevalence of alta patella position, and Insall-Salvati ratio were significantly higher in cases (P<0.001 for all), and cases had a higher incidence of trochlear dysplasia (P<0.001). There were no significant differences between cases and controls regarding patella baja. CONCLUSION: Anatomical knee variants, including the TT-TG distance, trochlear dysplasia, and Insall-Salvati ratio, are significant risk factors for PFOA progression. The results also indicate that higher BMI and older age are significantly associated with more measures of MRI Osteoarthritis Knee Score (MOAKS) than demographic information. Among anatomical variants, a higher TT-TG distance and an increased grade of trochlear dysplasia show a significant relationship with more measures of MOAKS. Understanding the relationship between these factors has important clinical and research implications and can help inform the development of new treatments.
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 38022726
BACKGROUND: Following parapneumonic effusions, malignant pleural effusions (MPEs) stand as the second most common cause of exudative pleural effusions. These effusions typically remain unresponsive to systemic chemothera...BACKGROUND: Following parapneumonic effusions, malignant pleural effusions (MPEs) stand as the second most common cause of exudative pleural effusions. These effusions typically remain unresponsive to systemic chemotherapy, necessitating novel therapeutic approaches. This study aims to ascertain the effectiveness of intrapleural injection with a 50% glucose solution and to compare it with intrapleural injection of Bleomycin sulfate in treating malignant pleural effusion. METHODS: This prospective, double-blind, randomized clinical trial was conducted at Al-Zahra Hospital in Isfahan. The study protocol gained approval from the Iranian Registry of Clinical Trials (IRCT code: IRCT20201013049017N1) (https://en.irct.ir/trial/52739). The study population encompassed patients with malignant pleural effusion. Sampling occurred through a census approach from October 2019 to March 2020. The first group received a pleurodesis solution containing 12.5 cc of 2% lidocaine with Bleomycin, while the second group received a solution comprising 200 cc of 50% glucose solution (10 grams of glucose) and 12.5 ml of 2% lidocaine, within the same volume. These solutions were injected into the pleural space via the chest tube. RESULTS: The complete response rate to treatment three months post-injection was 71.9% in the Bleomycin sulfate group and 65.6% in the 50% dextrose group. However, the difference between the two groups did not achieve statistical significance (P = 0.689). The incidence of post-injection fever and pain intensity exhibited comparability in both groups. CONCLUSION: The treatment involving a combination of 50% glucose solution with Bleomycin for pleurodesis in patients with malignant pleural effusion demonstrated outcomes akin to other treatment options.
Naderi Z, Amra B, Ahmadi F
… +1 more, Emami Ardestani M
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 37736504
BACKGROUND: Sleep disorders can significantly impair the quality of life and daily functions. Evaluating sleep quality can provide valuable information about working conditions. This study aims to evaluate the sleep qual...BACKGROUND: Sleep disorders can significantly impair the quality of life and daily functions. Evaluating sleep quality can provide valuable information about working conditions. This study aims to evaluate the sleep quality of faculty members at Isfahan University of Medical Sciences (IUMS). METHODS: This descriptive-analytic study was conducted from 2020 to 2021, involving 106 faculty members from the medical school. A questionnaire collected demographic information, including age, sex, height, weight, body mass index (BMI), level of education, history of faculty membership, major, working hours during the day and night, residency place, and medical history. The Pittsburgh Sleep Quality Index (PSQI) and Symptom Checklist-25 (SCL-25) questionnaire were used to assess participants' sleep quality. Data were compared between clinicians and basic science faculty members. RESULTS: PSQI subtypes were examined among the participants. The total PSQI score was 6.20±3.4. A comparison of PSQI scores and subtypes based on age categories did not show any significant differences (P > 0.05 for all). Clinicians had significantly lower total PSQI scores (P=0.044), sleep latency (P=0.024), sleep disturbances (P=0.012), and daytime dysfunction (P=0.022). Additionally, clinicians had a lower severity of sleep latency (P=0.024), sleep disturbances (P=0.012), and total PSQI score (P=0.044). However, clinicians exhibited a higher intensity of daytime dysfunction (P=0.022). CONCLUSION: Faculty members exhibited a high prevalence of sleep disorders, with the most common disorders being sleep disturbance and high sleep latency. The prevalence of sleep disorders was higher among basic science faculty members compared to clinicians.
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 37736503
Obstructive sleep apnea (OSA) is a sleep disorder of significant health concern with a high prevalence in the general population. It has been found to exhibit a high incidence of comorbidity with epilepsy, the exact unde...Obstructive sleep apnea (OSA) is a sleep disorder of significant health concern with a high prevalence in the general population. It has been found to exhibit a high incidence of comorbidity with epilepsy, the exact underlying pathophysiology of which still remains poorly understood. OSA is characterized by apnea/hypopnea spells and arousals, leading to intermittent hypoxemia and sleep deprivation. Both sleep deprivation and hypoxemia adversely affect the cortical excitability and favor epileptogenesis and worsening of pre-existing epilepsy, if any. In patients with OSA, deprivation of rapid eye movement sleep (REMS) phase (known for its strong antiepileptic influence) is relatively more than that non rapid eye movement sleep phase leading to postulation of REMS deprivation as a significant factor in the development of epilepsy as a comorbidity in patients with OSA. Furthermore, OSA and epilepsy both have shown to exercise a bidirectional influence on one another and are also likely to exacerbate each other through a positive feedback mechanism. This is especially based on the reports of improved control of epilepsy upon treatment of comorbid OSA. This brief paper attempts to present an underlying pathophysiological basis of the comorbidity of OSA and epilepsy based upon sleep deprivation and hypoxemia that are characteristic features observed in patients with OSA.
Yashchyshyn Z, Kozyk M, Strubchevska K
… +1 more, Ziablitsev S
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 37736502
OBJECTIVE: Determine the effect of different spectrum laser radiations on the expression of Glial Fibrillary Acidic Protein (GFAP) and allograft inflammatory factor-1 (Iba-1) in the sciatic nerve during regeneration. MET...OBJECTIVE: Determine the effect of different spectrum laser radiations on the expression of Glial Fibrillary Acidic Protein (GFAP) and allograft inflammatory factor-1 (Iba-1) in the sciatic nerve during regeneration. METHODS: The experiment was performed on 60 lab Wistar rats weighing 200-250 g. The left sciatic nerve was severed and subsequent end-to-end epineural suturing was performed 10, 20, 30, and 45 minutes after neurotomy. Western blot and immunohistochemistry analyses were performed by means of polyclonal anti-GFAP antibodies (Thermo Fisher Scientific, USA) and anti-Iba-1 antibodies (Invitrogen, USA) 90 days after nerve repair. RESULTS: The use of green and blue spectrum laser radiation significantly increased GFAP protein expression regardless of the time when surgical nerve repair was performed after injury. The expression of Iba-1 and tubulin after blue spectrum laser radiation with a wavelength of 470 nm was significantly higher than the control values by 5.1-11.0 times. An increase in the expression of Iba-1 and tubulin was noted when a green spectrum laser with a wavelength of 560 nm was utilized and nerve suturing was performed 10 and 20 minutes after nerve injury. The green spectrum laser with a wavelength of 520 nm had no significant effect on the expression of Iba-1 and tubulin. Morphologically, the highest proliferative reaction of glia was recorded when using a blue spectrum laser. CONCLUSIONS: Laser radiation with blue (470 nm) and green (560 nm) spectra, promoted the activation of GFAP-positive Schwann cells and nerve regeneration. Activation of microglia is a necessary component of nerve regeneration and the content of Iba-1 represented the efficiency of regeneration.
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 37457651
Despite the introduction of combined antiretroviral therapy (cART) HIV-1 virus persists in the brain in a latent or restricted manner and viral proteins, such as gp120, continue to play a significant disease-inciting rol...Despite the introduction of combined antiretroviral therapy (cART) HIV-1 virus persists in the brain in a latent or restricted manner and viral proteins, such as gp120, continue to play a significant disease-inciting role. Gp120 is known to interact with -methyl--aspartate (NMDA) receptors (NMDARs) resulting in neuronal injury. Glutamate is the main excitatory neurotransmitter in the brain and plays an important role in cognitive function and dysregulation of excitatory synaptic transmission impairs neurocognition. It is our hypothesis that gp120 may alter synaptic function via modulating glutamate function from a physiological molecule to a pathophysiological substance. To test this hypothesis, we studied the modulatory effects of gp120 and glutamate on NMDAR-mediated spontaneous excitatory postsynaptic current (sEPSC) and dynamic dendritic spine changes in rat cortical neuronal cultures. Our results revealed that gp120 and glutamate each, at low concentrations, had no significant effects on sEPSC and dendritic spines, but increased sEPSC frequency, decreased numbers of dendritic spines when tested in combination. The observed effects were blocked by either a CXCR4 blocker or an NMDAR antagonist, indicating the involvements of chemokine receptor CXCR4 and NMDARs in gp120 modulation of glutamate effects. These results may imply a potential mechanism for HIV-1-associated neuropathogenesis in the cART era.
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 37457650
BACKGROUND AND OBJECTIVE: Lysine is an essential amino acid involved in several biochemical pathways. It has been shown to enhance blood supply and target growth factors, leading to improved wound healing. The present st...BACKGROUND AND OBJECTIVE: Lysine is an essential amino acid involved in several biochemical pathways. It has been shown to enhance blood supply and target growth factors, leading to improved wound healing. The present study aimed to evaluate the efficacy and tolerability of a 15% lysine cream in treating diabetic foot ulcers, as measured by the Bates-Jensen Wound Assessment Tool (BWAT). MATERIALS AND METHOD: A randomized, open-label, interventional study was conducted on 40 volunteers with diabetic ulcers. The treatment group (n=20) received well-known treatment along with lysine cream (15%) twice daily, while the control group (n=20) received standard therapy alone. Wound healing was evaluated using the BWAT. The student t-test and one-way ANOVA were used to compare the clinical assessment parameters to the baseline. RESULTS: Both groups showed a significant decrease in ulcer size, depth, edges, undermining, necrotic tissue type, necrotic tissue amount, exudate type, and exudate amount over six weeks, with no significant difference between the groups after the first week. The lysine-treated group showed a significant improvement in wound healing compared to the control group (P<0.05). CONCLUSION: The present study demonstrates that a 15% lysine cream can significantly improve wound healing in diabetic foot ulcer patients, as measured by the BWAT, compared to standard treatment alone. Further research is needed to confirm these findings and to explore the underlying mechanisms of lysine's therapeutic effects.
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 37457649
BACKGROUNDS: Impaired sleep is independent risk factor of neurodegeneration and dementia. Chronic insomnia impairs melatonin (MEL) production that is directly proportionate to its duration. The underlying mechanisms link...BACKGROUNDS: Impaired sleep is independent risk factor of neurodegeneration and dementia. Chronic insomnia impairs melatonin (MEL) production that is directly proportionate to its duration. The underlying mechanisms linking sleep loss to dementia and the possible therapeutic effect of melatonin have not been fully elucidated. Previous research showed great controversy concerning the effects of paradoxical sleep deprivation (PSD) on body weight, serum lipoproteins, and inflammatory cytokines. GOALS: To examine the effect of chronic paradoxical sleep deprivation (PSD) with and without MEL supplementation on memory using RAWM, parameters of metabolic syndrome (MS), liver enzymes, serum cortisol, and inflammatory cytokines as well as liver, colon, and brain histopathology. METHODS: Forty rats were divided into four groups ten animals each; C: control, G: grid group, SD: sleep deprivation group, and SD+MEL sleep deprivation treated with melatonin. RESULTS: MEL supplementation reversed PSD-induced memory deficits (P<0.05), the elevation of serum cortisol (P<0.001), glucose (P<0.05), ALT (P<0.05), AST (P<0.001), TNF-alpha (P<0.001), IL-10 (P<0.01) and improved colon, liver, and brain architecture. Melatonin reduced body weight (P<0.05), total cholesterol, LDL-c, and triglycerides as well as increased HDL-c (P<0.001). CONCLUSION: MEL has a protective effect against chronic PSD-induced metabolic malfunction and cognitive deterioration by reducing stress, improving immunity, and maintaining colonic wall integrity.
Int J Physiol Pathophysiol Pharmacol
· 2023 · PMID 37457648
OBJECTIVES: The goal of this study was to evaluate a low fixed-dose versus weight-based dosing strategy for four-factor prothrombin complex (4F-PCC) time to administration in intracranial hemorrhage (ICH) patients. METHO...OBJECTIVES: The goal of this study was to evaluate a low fixed-dose versus weight-based dosing strategy for four-factor prothrombin complex (4F-PCC) time to administration in intracranial hemorrhage (ICH) patients. METHODS: A retrospective analysis was conducted at a single rural Tertiary referral center in patients ≥18 years old on warfarin with ICH who received 4F-PCC. Continuous variables were summarized using mean (±95% CI) and compared using two-tailed tests; values ≤0.05 were considered statistically significant. RESULTS: A total of 46 ICH patients were reversed using 4F-PCC (Fixed, n = 27 and Weight, n = 19). Baseline characteristics were equivalent. Total units of 4F-PCC (mean dose units 2525.1 versus 1623.3) and dose per kg were significantly reduced in the fixed-dose group. Total time from order to delivery was significantly reduced with the fixed-dose strategy (mean time 43.0 versus 29.0 minutes). Hospital length of stay (LOS), intensive care unit LOS, and mortality were equivalent with a similar mechanism. International Normalized Ratio (INR) reversal success (≤1.5) and total INR change was comparable with no difference in adverse thromboses between groups. CONCLUSIONS: A fixed-dosed strategy reduced time to 4F-PCC administration for warfarin reversal in ICH, as compared to a weight-based strategy; with no increase in LOS, mortality, or need for additional dosing. This also resulted in significant cost savings.