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Acta Biochimica Et Biophysica Sinica May 2024Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects...
Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.
PubMed: 38808395
DOI: 10.3724/abbs.2024049 -
International Journal of Molecular... May 2024Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects...
Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A and A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline. The assessments included catalepsy testing on the bar and gait analysis using the Open Field Maze. A two-way repeated-measures analysis of variance (ANOVA), followed by Tukey's post hoc tests, was employed to evaluate the impact of groups (experimental × control), aminophylline (60 nM × 120 nM × saline/placebo), and interactions. Significance was set at 5%. The results revealed that the systemic administration of haloperidol in the experimental group increased catalepsy and dysfunction of gait that paralleled the observations in PD. Co-treatment with aminophylline at 60 nM and 120 nM reversed catalepsy in the experimental group but did not restore the normal gait pattern of the animals. In the non-PD induced group, which did not present any signs of catalepsy or motor dysfunctions, the intracerebral dose of aminophylline did not exert any interference on reaction time for catalepsy but increased walking distance in the Open Field Maze. Considering the results, this study highlights important adenosine interactions in the basal ganglia of animals with and without signs comparable to those of PD. These findings offer valuable insights into the neurobiology of PD and emphasize the importance of exploring novel therapeutic strategies to improve patient's catalepsy and gait.
Topics: Animals; Catalepsy; Mice; Male; Aminophylline; Disease Models, Animal; Gait; Haloperidol; Parkinson Disease
PubMed: 38791229
DOI: 10.3390/ijms25105191 -
Novel Gene Mutation c.118G>A Causing Keratinocyte and Cardiomyocyte Disconnection in Darier Disease.Biomedicines May 2024Darier disease (DD) is an autosomal dominant disorder due to pathogenic variants of the gene that causes an isolated skin manifestation based on keratinocyte...
Darier disease (DD) is an autosomal dominant disorder due to pathogenic variants of the gene that causes an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far, although a high incidence of neuropsychiatric syndromes suggests an involvement of the central nervous system. We report that the pathogenic ATP2A2 gene variant c.118G>A may cause cardiac involvement in patients with DD, consisting of keratinocyte and cardiomyocyte disconnection. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsies because cardiac dilatation and dysfunction appeared several decades after skin manifestations. Keratinocyte disconnection was paralleled by cardiomyocyte separation at the lateral junction. Cardiomyocyte separation was associated with cell disarray, sarcoplasmic reticulum dilatation, and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules are associated with chest pain, severe muscle exhaustion, and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation. Cardiac pathologic changes are similar to those documented in the skin, including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors that enhance SERCA2 protein phosphorylation may substantially attenuate the symptoms.
PubMed: 38791022
DOI: 10.3390/biomedicines12051060 -
Anesthesiology and Pain Medicine Dec 2023The sympatholytic property of dexmedetomidine (DEX) makes it suitable as a hypotensive drug during functional endoscopic sinus surgery (FESS); however, delayed emergence...
Effect of Intravenous Aminophylline on Hemodynamics and Recovery of Patients Undergoing Functional Endoscopic Sinus Surgery Under Dexmedetomidine Hypotensive Anesthesia: A Randomized Controlled Study.
BACKGROUND
The sympatholytic property of dexmedetomidine (DEX) makes it suitable as a hypotensive drug during functional endoscopic sinus surgery (FESS); however, delayed emergence from anesthesia and high postoperative sedation have been reported.
OBJECTIVES
Delayed emergence from anesthesia and high postoperative sedation are associated with a prolonged length of stay in the operating room and the postanesthesia care unit (PACU), which increases health care costs. This study aimed to overcome the negative impact of DEX on recovery by using aminophylline.
METHODS
This randomized, double-blind, placebo-controlled study was conducted on 52 patients planned for elective FESS under general anesthesia with DEX infusion for controlled hypotension during surgery. Patients were equally divided into 2 groups. The aminophylline group received 4 mg/kg aminophylline diluted in 50 mL saline 0.9% over 30 minutes after positioning in a 20-degree reverse Trendelenburg position. The control group received 50 mL saline 0.9% with a similar volume and period as the aminophylline group.
RESULTS
The extubation time was significantly shorter in the aminophylline group (6.5 (5.25 - 7.75) minutes) than in the control group (9 (7.25 - 10) minutes) (P-value < 0.001). The PACU discharge time was significantly shorter in the aminophylline group (15 (10 - 20) minutes) compared to the control group (20 (15 - 28.75) minutes) (P-value = 0.036). Intraoperative heart rate and mean arterial pressure were nonsignificantly different between the 2 groups. Ramsay sedation score measurements at 15 min, 30 min, and 60 min after extubation were significantly lower in the aminophylline than in the control group (P-value < 0.05). Complications were nonsignificantly different between the 2 groups.
CONCLUSIONS
Intraoperative aminophylline infusion enhances the recovery of patients undergoing FESS under DEX hypotensive anesthesia without intraoperative hemodynamic alterations and decreases their postoperative sedation without significant postoperative side effects.
PubMed: 38721439
DOI: 10.5812/aapm-141669 -
Alternative Therapies in Health and... Apr 2024To study and compare the efficacy and clinical value of aminophylline and doxofylline in the clinical treatment of chronic obstructive pulmonary disease (COPD).
OBJECTIVE
To study and compare the efficacy and clinical value of aminophylline and doxofylline in the clinical treatment of chronic obstructive pulmonary disease (COPD).
METHOD
The study analyzed the clinical data of 92 patients with chronic obstructive pulmonary disease who received either aminophylline or doxofylline treatment in the hospital from January 2020 to June 2022. The patients were divided into a control group composed of 46 COPD patients who received aminophylline treatment and a study group composed of 46 COPD patients who received doxofylline treatment. The two groups' total effective rate and incidence of adverse reactions were compared. The serum inflammatory factor indicators, symptom scores, pulmonary ventilation function, arterial blood gas, chest and lung responsiveness, sleep status indicators, and quality of life scores of the two groups before and after treatment were compared.
RESULTS
At the end of treatment, the total effective rate was higher in the study group compared to the control group (P < .05). Regarding adverse reactions, the study group's total incidence was lower than the control group's (P < .05). After treatment, the levels of serum inflammatory factor indicators of CRP, PCT, and TNF- α in both groups were decreased compared with those before treatment; while comparing the above indicators between the groups, it was found that the values in the study group were lower (all P < .05). After treatment, the scores of symptoms such as cough, expectoration, and shortness of breath in both groups of patients were significantly lower than before treatment, while compared to the control group, the scores of all symptoms were lower in the study group (P < .05). After treatment, compared with FEV1, FEV1/FVC, PaO2, and PaCO2 before treatment, the above indicators in both groups were significantly improved. However, compared with various indicators in the control group, the values of FEV1, FEV1/FVC, and PaO2 in the study group were higher, while the values of PaCO2 in the study group were lower (all P < .05). After treatment, the measured values of indicators such as thoracic compliance, lung compliance, and total compliance in the two groups were significantly higher compared with those before the treatment, while compared to the control group, the values of all indicators in the study group were higher (P < .05). After treatment, compared with the control group's monitoring of various indicators of nighttime sleep, the study group obtained better data on monitoring of sleep latency and actual sleep duration. The group obtained lower scores in sleep quality evaluation, while the two groups significantly improved their sleep-related data in night-time monitoring and evaluation compared to those before treatment, with all P < .05. After treatment, the scores in various aspects of the quality of life of patients in both groups were significantly increased compared to those before treatment, and after comparing the scores of various quality of life between the two groups, it was found that the study group was higher than the control group (all P < .05).
CONCLUSION
After the onset of COPD, doxofylline treatment can achieve better effects than aminophylline treatment.
PubMed: 38607196
DOI: No ID Found -
Cureus Jan 2024Post-dural puncture headache (PDPH) is occasionally an inevitable side effect of neuraxial anesthesia, which can happen after spinal anesthesia or if an accidental dural... (Review)
Review
Post-dural puncture headache (PDPH) is occasionally an inevitable side effect of neuraxial anesthesia, which can happen after spinal anesthesia or if an accidental dural puncture (ADP) happens during epidural anesthesia. The treatment and prevention options for PDPH differ widely from one institution to another. The management of PDPH is heterogeneous in many institutions because of the absence of clear guidelines and protocols for the management of PDPH. This study aimed to summarize all articles published during the past decade that discussed the treatment or prevention of PDPH. From 2013 to 2023, 345 publications were filtered for all treatment and prevention approaches used for PDPH patients. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines were followed for conducting this systematic review, and 38 articles were included for analysis and review. Existing data come from small randomized clinical trials and retrospective or prospective cohort studies. This review supports the effect of oral pregabalin and intravenous aminophylline in both treatment and prevention. Intravenous mannitol, intravenous hydrocortisone, triple prophylactic regimen, and neostigmine plus atropine combination showed effective and beneficial outcomes. On the other hand, neither neuraxial morphine nor epidural dexamethasone showed promising results. Consequently, the use of neuraxial morphine or epidural dexamethasone for the prevention of PDPH remains questionable. Regarding the posture of the patient and its consequences on the incidence of the headache, lateral decubitus is better than a sitting position, and a prone position is better than a supine position. Smaller non-cutting needles play a role in avoiding PDPH. Minimally invasive nerve blocks, including sphenopalatine ganglion or greater occipital nerves, are satisfyingly effective. Epidural blood patches remain the more invasive but the gold standard and ultimate solution in patients resisting medical therapy. This study highlights the need for larger research to define the best approach to prevent and treat PDPH.
PubMed: 38361721
DOI: 10.7759/cureus.52330 -
Skin Research and Technology : Official... Feb 2024The review delves into the realm of reducing submental fat, presenting a comprehensive analysis of various lipolytic agents used in plastic surgery and dermatology. The... (Review)
Review
The review delves into the realm of reducing submental fat, presenting a comprehensive analysis of various lipolytic agents used in plastic surgery and dermatology. The introduction establishes the context by defining the key indicators of a youthful neck and emphasizing the significant influence of fat in the aging process, particularly in the submental area. The usage of aminophylline involves subcutaneous injections, facilitating fat breakdown by increasing cyclic adenosine monophosphate and inhibiting adenosine receptors. Hypotonic pharmacologic lipo-dissolution induces fat dissolution via injected compounds under pressure, while lipolytic lymphatic drainage employs hyaluronidase to reduce tissue viscosity, aiding fat circulation. Glycerophosphorylcholine containing choline alfoscerate claims to activate fat metabolism, whereas the utilization of phosphatidylcholine combined with deoxycholate lacks cosmetic approval due to safety concerns. Deoxycholic acid has FDA approval for submental fat reduction, yet its mechanisms remain incompletely understood. Understanding the complex anatomy and mechanisms of lipolytic agents is essential for safe and effective submental fat reduction, despite evolving practices and off-label utilization. Clinical guidelines and references support this discussion, offering insights for safer applications.
Topics: Humans; Adipose Tissue; Deoxycholic Acid; Cosmetic Techniques; Injections, Subcutaneous; Aminophylline; Subcutaneous Fat
PubMed: 38297988
DOI: 10.1111/srt.13601 -
Critical Care and Resuscitation :... Jun 2022Medications prescribed for indications or at doses, frequencies or durations not approved by the Australian Therapeutic Goods Administration are considered "off- label"....
Medications prescribed for indications or at doses, frequencies or durations not approved by the Australian Therapeutic Goods Administration are considered "off- label". Critical illness makes seeking consent for off-label medication use impractical. We aimed to characterise the extent of off-label medication use in a tertiary medical- surgical intensive care unit (ICU) by auditing the electronic health records of all patients admitted over a one-month period. We found 25.4% of 2292 prescriptions made for 142 patients were off-label. Eighty-one (37.2%) of the total of 218 different prescribed medications were used at least once for an off-label indication. Medications commonly prescribed off-label included antacids (pantoprazole, esomeprazole), analgesics (fentanyl, morphine, ketamine, pregabalin), anticonvulsants (levetiracetam), antibiotics (cefazolin, erythromycin), antipsychotics (quetiapine, haloperidol), and cardiovascular agents (metoprolol, clonidine). Nearly all patients (88.0%) received at least one off-label medication during their ICU stay. Most off- label medications were used for conventional (albeit not licensed) reasons, but nine out of 81 (11.1%) were not; for example, acetazolamide for hypertension, aminophylline for oliguria, and dexmedetomidine for seizures. Recognising the challenges of formally registering an indication with the Therapeutic Goods Administration, but also the value of reducing the incidence of medications used for potentially incorrect purposes, we suggest guideline endorsement of what constitutes standard critical care practice as an alternative to regulatory control.
PubMed: 38045597
DOI: 10.51893/2022.2.OA8 -
Journal of Anaesthesiology, Clinical... 2023The return of consciousness (ROC) after general anesthesia (GA) is by stopping the administration of anesthetic agents. At present, no drug is given to reverse the loss...
Comparison of the effects of caffeine, aminophylline, and saline on the recovery from total intravenous anesthesia in laparoscopic surgeries: A randomized controlled trial.
BACKGROUND AND AIMS
The return of consciousness (ROC) after general anesthesia (GA) is by stopping the administration of anesthetic agents. At present, no drug is given to reverse the loss of consciousness produced by general anesthetic agents. This study is conducted to find whether caffeine and aminophylline hasten the ROC.
MATERIAL AND METHODS
This study was conducted on 75 American Society of Anesthesiologists (ASA) I and II female patients undergoing laparoscopic hysterectomy, aged between 18 and 60 years. The patients were divided into three equal groups (Group C: caffeine citrate, Group A: aminophylline, and Group S: saline) of 25 each by a computer-generated random number table. GA was induced with propofol, fentanyl, and maintained with propofol infusion. On completion of the surgery, the neuromuscular blocking agent was reversed and then the infusion of propofol was stopped. The study drug was administered intravenously when the BIS 60 was achieved. Time to achieve BIS 90, return of first gag reflex, eye-opening on verbal command, and extubation after study drug administration were noted. Hemodynamic parameters and SpO2 were also monitored.
RESULTS
The time for BIS 60 to 90 was 10 (4.25) min in the caffeine group, 13 (4.25) min in the aminophylline group, and 26 (9.0) min in the saline group. The time to return of gag reflex and time to extubation were shorter in the caffeine and aminophylline group compared to the saline group. The time to eye-opening on verbal command was shorter in the aminophylline group compared to the saline group. Hemodynamic parameters after infusion of the study drug were comparable in all three groups.
CONCLUSION
Caffeine hastens the recovery from total intravenous anesthesia with propofol and fentanyl in laparoscopic hysterectomy as effectively as aminophylline.
PubMed: 38025567
DOI: 10.4103/joacp.joacp_528_21