International journal of physiology, pathophysiology and pharmacology最新文献

Background and objective: For the management of postoperative pain, opioids have typically been half their efficacy, but they are associated with notable side effects such as sedation, nausea, and respiratory depression. Nefopam is a non-opioid analgesic, within the benzoxazocine class, that has been suggested as an important adjunctive analgestic in multimodal analgesia (MMA). However, the extent to which analgesics outside of opioids are accepted as part of Enhanced Recovery After Surgery (ERAS) programs is controversial. The difficulty of predicting pain management outcome, considering the variability in postoperative pain, means that study of the analgesic effect of intravenous nefopam given different strategies, is essential in the use of nefopam for spinal surgery.

Methods: We completed a systematic search of PubMed, Scopus, and Google Scholar until July 20, 2025. We included randomized controlled trials (RCTs) that assessed intravenous nefopam for treating postoperative pain in patients who had spine surgery. The extracted data were pooled, and we performed a random-effects meta-analysis. Subgroup analyses were planned to compare bolus use, infusion use, and bolus plus infusion use.

Results: Seven RCTs, involving a total of 471 patients, were included in the eligibility criteria. The overall pooled analysis found no differences in postoperative pain scores between the nefopam and control conditions. The standardized mean difference (SMD) was -0.28 (95% confidence interval [CI]: -0.74 to 0.18), which indicated no difference in efficacy. The sub-group analysis found that bolus administration had the greatest analgesic effect (SMD = -0.70) and infusion or bolus + infusions had little or no clinical benefit. The infusion sub-group had the greatest heterogeneity (I² = 86.9%) suggesting variability in studies for this delivery method.

Conclusion: The use of intra-venous nefopam offers a small analgesic benefit in spine surgery, which is best seen when applied intermittently or as a bolus rather than as a continuous infusion. Though it is not particularly effective as a standalone agent, bolus does have potential as an adjunct and should be included as part of a more multimodal analgesia approach. Further high quality RCTs with larger sample sizes are warranted to better define the optimal application of nefopam and dosing in patients undergoing spinal surgery.

Background: Postoperative pain management in spine surgery is challenging. While opioids are effective, their significant adverse effects, including respiratory depression, necessitate opioid-sparing strategies. The Erector Spinae Plane (ESP) block has emerged as a promising regional technique. This study investigates whether the addition of methylprednisolone to bupivacaine in an ESP block enhances postoperative analgesia and reduces opioid consumption in patients undergoing lumbar spine surgery.

Method: This prospective, randomized clinical trial (Ethical Approval ID: IR.SBMU.RETECH.REC.1403.467) included 64 patients (18-65 years) for two- or three-level lumbar spine surgery. Patients were randomized into two groups: the control group (bupivacaine alone) and the intervention group (bupivacaine combined with methylprednisolone). Data were collected on intraoperative metrics (e.g., fluid therapy, blood loss, operation time), opioid consumption, postoperative pain scores (NRS), incidence of nausea and shivering, blood glucose levels, and need for rescue analgesia up to one month post-surgery.

Results: The methylprednisolone group showed significantly lower narcotics consumption (intraoperatively and in the PACU). The pain level (NRS) was also lower in this group for up to four weeks post-operation. There were no significant inter-group differences in surgery duration, anesthetic consumption, bleeding, or the incidence of nausea and chills.

Conclusion: The use of methylprednisolone as an adjuvant to bupivacaine in the ESP block improves the quality and duration of analgesia in spine surgery patients. However, the transient elevation in blood glucose levels highlights the need for careful glucose monitoring.

Anthracyclines are vital chemotherapy drugs for treating various cancers, including solid tumors and blood cancers; however, they cause dose-dependent cardiotoxicity, manifesting as cardiomyopathy, arrhythmias, and heart failure (HF). Cardiotoxicity, driven by oxidative stress, mitochondrial dysfunction, and other mechanisms, limits its use and affects long-term patient outcomes. Meanwhile, sodium-glucose co-transporter-2 (SGLT2) inhibitors, originally developed for type 2 diabetes, offer cardiovascular benefits beyond glucose control, such as reduced HF hospitalization and mortality. These benefits stem from improved myocardial energetics, reduced fibrosis, and improved regulation of cardiac ion homeostasis. Experimental studies, including animal models, have shown that SGLT2 inhibitors, such as empagliflozin, preserve cardiac function and reduce inflammation in anthracycline-induced cardiotoxicity. Clinical data, although limited to small retrospective studies, suggest lower mortality and fewer cardiovascular events in anthracycline-treated cancer patients using SGLT2 inhibitors. However, variability in the study design highlights the need for a systematic evaluation. This systematic review aimed to critically assess the cardiovascular outcomes associated with SGLT2 inhibitor use in cancer patients treated with anthracyclines, evaluating their dual role in glycemic control and cardioprotection, and to identify evidence gaps to inform therapeutic strategies for optimizing long-term cardiovascular health in this vulnerable population.

Alpha-N-acetylgalactosaminidase (nagalase), a lysosomal enzyme encoded by the NAGA gene, plays a critical role in the degradation of glycoconjugates, modulation of immune responses, and regulation of vitamin D metabolism. Dysregulation of nagalase is associated with several pathological conditions, including Schindler disease, psychiatric disorders, viral infections, and notably, cancer. Elevated serum levels of nagalase, particularly the Naga6 isoform, have been observed in cancer patients and individuals with enveloped viral infections, contributing to immune evasion by impairing macrophage activation through Gc protein deglycosylation. Moreover, nagalase activity has been implicated in rare blood group changes observed in some malignancies. Although ELISA-based assays offer potential for quantifying nagalase, their clinical application is hindered by assay interferences and cross-reactivity. The immunotherapeutic potential of Gc protein-derived macrophage activating factor (GcMAF), in combination with vitamin D3 and ascorbate, has shown promise in enhancing anti-tumor immunity, particularly in prostate cancer. Nevertheless, conflicting data and methodological criticisms have led to skepticism regarding its efficacy. This review comprehensively explores the biochemical variants of nagalase, its physiological and pathological roles, its diagnostic utility as a biomarker, and emerging therapeutic strategies targeting its activity, including gene silencing and monoclonal antibody development. The findings underscore the need for rigorous clinical studies to validate the diagnostic and therapeutic potential of nagalase in oncology and immunology.

Background: The diagnosis and follow-up of Crohn's disease (CD) often require invasive instrumental examinations, which carry a high risk of iatrogenic injury. This study aimed to determine the frequency of ultrasound features in each stage of the Pediatric Crohn's Disease Activity Index (PCDAI).

Methods: This cross-sectional study included 22 pediatric patients with Crohn's disease. Disease activity was assessed using the PCDAI. The state of CD activity was categorized into four groups: remission (PCDAI scores less than 10), mild (PCDAI scores of 10-27.5), moderate (PCDAI scores of 30-37.5), and severe (PCDAI scores > 40). Clinical data collected included the thickness of the ascending colon loop, the thickness of the ileal loop, the number of lymph nodes, the short-axis diameter of lymph nodes (mm), spleen span, presence of free fluid, fistulas, liver echogenicity, vascularity around the loops, lumen narrowing, terminal ileum compression, mesenteric fat hypertrophy, intestinal wall and mesenteric fat echogenicity, and Superior Mesenteric Artery indices. These data were documented for analysis.

Results: As disease activity progressed from mild to severe, intestinal wall echogenicity, fat echogenicity, mesenteric fat, vascularity, and lumen narrowing significantly increased (P < 0.05). The mean ileal loop thickness also significantly increased (P = 0.005), rising from 2.12 ± 0.58 in mild cases to 4.49 ± 1.43 in severe cases. However, the mean ascending colon loop thickness, the number of lymph nodes, the short-axis diameter of lymph nodes, and spleen span were not statistically significant (P > 0.05). Changes in the superior mesenteric artery indices across the different PCDAI phases were also not statistically significant (P > 0.05).

Conclusions: Ultrasound is a convenient and reproducible tool for monitoring CD activity in pediatrics. This study demonstrated significant findings, including the increase in intestinal wall echogenicity, fat echogenicity, mesenteric fat hypertrophy, vascularity, and lumen narrowing as the disease activity progressed from mild to severe. Particularly, the mean ileal loop thickness showed a significant increase in the severe phase compared to the mild phase.

Effective management is one of the most important factors in mitigating postoperative endodontic pain (PEP). The purpose of this network meta-analysis was to compare the therapeutic effects and safety of different drugs commonly used for pain relief after non-surgical endodontic treatment. We searched the Scopus, PubMed, and Google Scholar databases until February 2024. Titles, abstracts, and full texts were identified according to predetermined criteria. Data were extracted from the selected publications, and a quality assessment was performed for the included studies. Sixteen RCTs with 2,021 participants were included in the meta-analysis. All included studies investigated the impact of NSAIDs on pain reduction in nonsurgical endodontic treatment. A statistically significant reduction in pain was observed at 8 h (pooled effect = -3.10, I² = 100%), 12 h (pooled effect = -1.69, I² = 99.2%), 24 h (pooled effect = -1.48, I² = 99.9%), 48 h (pooled effect = -1.42, I² = 99.4%), and 72 h (pooled effect = -0.64, I² = 73.1%) of follow-up. The funnel plot was symmetrical, and sensitivity analysis excluded one article in 72 h follow-up. Overall, this meta-analysis demonstrated that NSAIDs and corticostreoids are statistically effective in relieving pain after non-surgical endodontic treatment. However, owing to the significant differences between studies and heterogenicity, additional randomized controlled trials are needed to validate this correlation further.

Objectives: Clinically, liver regeneration is often impaired by infections causing endotoxemia, although mechanisms are unclear. Since energy supply is essential for liver regeneration, we assessed whether formoterol (FMT), a β₂-adrenergic agonist that increases peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), the master regulator of mitochondrial biogenesis (MB), restores liver regeneration after partial hepatectomy (PHX) in endotoxin (LPS)-treated mice.

Methods: Mice underwent sham-operation, two-thirds PHX, PHX with LPS injection (PHX+LPS, 5 mg/kg, i.p.), or PHX+LPS followed by FMT (0.1 mg/kg, i.p.) after 2 h.

Results: At 48 h after PHX, 5'-bromo-2'-deoxyuridine incorporation, mitotic cells, proliferating cell nuclear antigen, and cyclin-D1 markedly increased, signifying liver regeneration. By contrast, after PHX+LPS, liver regeneration was almost completely suppressed. FMT restored liver regeneration after PHX+LPS. PGC1α, mitochondrial transcription factor-A (controlling mitochondrial DNA replication/transcription), and mitochondrial oxidative phosphorylation proteins ATP synthase-β and NADH dehydrogenase-3 decreased after PHX+LPS, signifying suppressed MB. FMT largely reversed these effects. Mitochondrial oxidative stress stimulates inflammation by activating inflammasomes. In addition to promoting MB, PGC1α reportedly inhibits oxidative stress and inflammation. 8-Hydroxy-deoxyguanosine, NLRP3, and inflammatory cytokines increased after PHX+LPS, demonstrating increased oxidative stress and inflammasome activation. Many necro-inflammatory foci occurred in liver sections after PHX+LPS. FMT increased expression of antioxidant protein thioredoxin-2, decreased oxidative stress, and blunted inflammatory responses. Additionally, FMT decreased alanine aminotransferase release and necrosis caused by PHX+LPS.

Conclusions: FMT restores liver regeneration during endotoxemia and decreases liver injury and inflammation, most likely by increasing PGC1α. Therefore, FMT is a promising therapy for liver failure caused by loss of liver mass complicated with sepsis.

Cardiomyopathy associated with amphetamine-dextroamphetamine (Adderall) use is an emerging and under-recognized clinical concern, particularly in the context of chronic stimulant exposure. While most reported cases involve non-ischemic myocardial dysfunction, the potential for Adderall to accelerate atherosclerosis and contribute to ischemic cardiomyopathy remains unexplored. This case report aims to document the potential severity of Adderall-induced cardiomyopathy with concomitant coronary artery disease (CAD), examine the pathophysiological link between chronic stimulant exposure and accelerated atherosclerosis, and emphasize the need for vigilant cardiovascular monitoring in patients on long-term stimulant therapy. We report the case of a 43-year-old man with no known cardiovascular history who presented with progressive dyspnea and signs of heart failure. He disclosed a five-year history of high-dose Adderall use (45-65 mg daily) and tobacco consumption but had no prior history of hypertension, diabetes, or known CAD. Evaluation revealed a severely reduced left ventricular ejection fraction (10-15%), consistent with dilated cardiomyopathy. Coronary angiography unexpectedly revealed severe three-vessel CAD, necessitating urgent coronary artery bypass grafting (CABG). Postoperative recovery was uneventful, and the patient was initiated on guideline-directed heart failure therapy, with structured follow-up and strict recommendations for stimulant cessation and lifestyle modification. This case illustrates the multifactorial cardiotoxicity of chronic Adderall use, including direct myocardial injury, fibrotic remodeling, vasospasm, and accelerated coronary atherosclerosis. Unlike prior reports of reversible non-ischemic cardiomyopathy, this case required surgical revascularization, underscoring the irreversible nature of the damage in some patients. It uniquely highlights the synergistic contribution of stimulant-induced toxicity and underlying CAD to the development of severe cardiac dysfunction.

Cardiac amyloidosis (CA) is a challenging acquired heart disease caused by the deposition of β-pleated amyloid proteins, often leading to nonspecific symptoms that complicate the diagnosis. This case report describes an 83-year-old male patient presenting with chest pain and cough, revealing significant cardiomegaly and pericardial effusion on imaging. Initial diagnostic modalities, including echocardiography and endomyocardial biopsy (EMB), have yielded inconclusive results. Despite a negative EMB result, further investigation using positron emission tomography/computed tomography ruled out cardiac sarcoidosis. A second EMB was performed to confirm the diagnosis of CA. This case underscores the importance of combining clinical symptoms with paraclinical assessments and advocating additional testing when discrepancies arise, highlighting the complexities in diagnosing CA. This case report emphasizes the necessity for clinicians to integrate clinical symptoms with diagnostic findings when assessing for cardiac amyloidosis. This illustrates the potential for false-negative biopsies and the importance of considering further testing to ensure an accurate diagnosis, ultimately enhancing diagnostic accuracy and patient management in cases of suspected cardiac amyloidosis.

Sarcopenia is an age-associated progressive deterioration of skeletal muscle, not only affecting the muscle function of elderly individuals but also contributing to various health issues and increased mortality. Current diagnostic tools are faced with limitations, hindering their widespread clinical application. This review examines the potential of myokines, peptides released from contracting muscles, as innovative biomarkers for sarcopenia. We explore the wide range of auto-, para-, and endocrine functions of myokines and the pathways of their physiological action, as well as address ongoing research results on the role of myokines as biomarkers for the timely diagnosis of sarcopenic individuals. Of all myokines, the ones that show the highest potential include irisin, myostatin, follistatin and brain-derived neurotrophic factor (BDNF). Their physiological action is exerted through complex pathways involving multiple molecules. Most studies show that these molecules can be used as biomarkers for the timely diagnosis of sarcopenia, whether by using each one individually or as a panel of biomarkers. However, several studies showed no correlation between the plasma levels of these peptides and a sarcopenia diagnosis. Finally, a number of studies also exhibited gender-affected relationships. While the quality of studies is promising, research on the use of myokines as biomarkers of sarcopenia is needed to more accurately determine the cut-off plasma values of such markers. By overcoming the shortcomings of existing methodologies, utilizing myokines in daily clinical practice could offer a promising path toward more effective prevention, diagnosis, and treatment strategies, ultimately improving outcomes for the aging population.