Efficacy of melatonin in alleviating disorders arising from repeated exposure to sevoflurane in males and females of the Wistar rats during preadolescence.

Pediatricians use sevoflurane due to its fast action and short recovery time. However, studies have shown that repeated exposure to anesthesia can affect learning and memory. Melatonin, an indole-type neuroendocrine hormone, has significant anti-inflammatory, and neuroprotective properties. Melatonin's impact on cognitive behavior in sevoflurane-anesthetized males and females of the Wistar rats during preadolescence was examined in this research. The cognitive function was evaluated by shuttle box and morris water maze tests, while interleukin-10, Catalase (CAT), Malondialdehyde (MDA), and Tumor Necrosis Factor-α (TNF-α) were evaluated using ELISA kits. The expression levels of the apoptosis-linked proteins, Bax, Bcl-2, and caspase-3, were determined using the western blotting technique. The learning and memory latencies of the rats were more significant in the sevoflurane groups than in the control group; however, the latencies were significantly shorter in the sevoflurane and melatonin groups than in the control group. The levels of MDA, TNF-α, Bax, and caspase-3 were significantly higher in the sevoflurane groups than in the control group. We also found that the levels of CAT and Bcl-2 were significantly reduced in the sevoflurane groups compared to the control group. Increasing levels of CAT, Bcl-2, and decreasing levels of MDA, TNF-α, Bax, and caspase-3 in response to melatonin indicate a possible contribution to the recovery from the sevoflurane impairment. Melatonin shows neuroprotective effects in male and female rats with sevoflurane-induced cognitive impairment. This suggests melatonin could be a valuable treatment for learning and memory deficits resulting from repeated exposure to sevoflurane, possibly by controlling apoptosis, oxidative stress, and inflammation.

Cellular and molecular mechanisms involved in the analgesic effects of botulinum neurotoxin: A literature review.

Botulinum neurotoxins (BoNTs), derived from Clostridium botulinum, have been employed to treat a range of central and peripheral neurological disease. Some studies indicate that BoNT may be beneficial for pain conditions as well. It has been hypothesized that BoNTs may exert their analgesic effects by preventing the release of pain-related neurotransmitters and neuroinflammatory agents from sensory nerve endings, suppressing glial activation, and inhibiting the transmission of pain-related receptors to the neuronal cell membrane. In addition, there is evidence to suggest that the central analgesic effects of BoNTs are mediated through their retrograde axonal transport. The purpose of this review is to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions. Most of the studies reviewed in this article were conducted using BoNT/A. The PubMed database was searched from 1995 to December 2022 to identify relevant literature.

Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults.

In pre-adolescence, repeated anesthesia may be required for therapeutic interventions. Adult cognitive and neurobehavioral problems may result from preadolescent exposure to anesthetics. This study examined the long-term morphological and functional effects of repeated sub-anesthetic doses of ketamine exposure on male and female rat adults during pre-adolescence. Weaned 48 pre-adolescent rats from eight mothers and were randomly divided into four equal groups: control group and the ketamine group of males and females (20 mg/kg daily for 14 days); then animals received care for 20-30 days. Repeated exposure to sub-anesthetic doses of ketamine on cognitive functions was assayed using Social discrimination and novel object tests. Besides, an elevated plus maze and fear conditioning apparatus were utilized to determine exploratory and anxiety-like behavior in adults. Toluidine blue stain was used to evaluate the number of dead neurons in the hippocampus, and the effects of ketamine on synaptic plasticity were compared in the perforant pathway of the CA1 of the hippocampus. Our study indicates that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can result in neurobehavioral impairment in male and female rat adulthood but does not affect anxiety-like behavior. We found a significant quantifiable increase in dark neurons. Recorded electrophysiologically, repeat sub-anesthetic doses of ketamine resulted in hampering long-term potentiation and pair pulse in male adult animals. Our results showed that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can induce hippocampus and neuroplasticity changes later in adulthood. This study opens up a new line of inquiry into potential adverse outcomes of repeated anesthesia exposure in pre-adolescent rats.

Long-term bumetanide administration altered behavioral pattern in mosaic Down's Syndrome: A case report.

The behavioral phenotypes emerge from cognitive architecture comprising attention, executive functions, and primary communication skills that all have shown remarkable deficits in Down's Syndrome (DS). These states arise from the proper functional interactions of the contributing neurotransmission and neuromodulation systems and other coding platforms. Gamma-aminobutyric acid (GABA) is an integral part of the neural interaction and regulation networks that its reverse action leads to broad detrimental consequences. This inhibitory substance needs an appropriate balance of co-transporters that largely shape the ionic milieu. Bumetanide, a specific NKCC1 inhibitor used for an eighteen-month interval, showed promising effects in restoring some behavior deficits in a fourteen-year-old boy diagnosed with genetically confirmed mosaic Down's Syndrome.

Comparison of the Effect of Intra-Articular, Periarticular, and Combined Injection of Analgesic on Pain Following Total Knee Arthroplasty: A Double-Blinded Randomized Clinical Trial.

The aim of this study was to compare the efficacy of 3 methods of intraoperative analgesic cocktail injection during total knee arthroplasty (TKA)-intra-articular (IA), periarticular (PA), and combined intra-articular and periarticular (IA+PA)-on controlling early postoperative pain. Methods: This was a prospective double-blinded parallel randomized clinical trial. A total of 153 patients scheduled for TKA were allocated to IA, PA, or IA+PA (51 patients each) by block randomization. The primary outcome was morphine consumption. Secondary outcomes were visual analogue scale (VAS) pain, knee flexion, straight leg raising, Knee Society Score (KSS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results: The morphine consumption was lowest in the PA group (median = 0, interquartile range [IQR] = 5) and highest in the IA group (median = 10, IQR = 5). The PA group had significantly lower VAS pain at rest than either IA (mean difference = -0.70; 95% confidence interval [CI] = -0.93 to -0.46; p < 0.001) or PA+IA (mean difference = -0.41; 95% CI = -0.65 to -0.18; p < 0.001). The PA group had also lower VAS pain during activity compared with IA (mean difference = -0.63; 95% CI = -0.85 to -0.40; p < 0.001) and IA+PA (mean difference = -0.38; 95% CI = -0.61 to -0.16; p < 0.001). The PA group had significantly greater active knee flexion compared with IA (mean difference = 9.68°; 95% CI = 5.50° to 13.86°; p < 0.001) and IA+PA (mean difference = 5.13°; 95% CI = 0.95° to 9.31°; p = 0.010). Passive knee flexion was greater for PA than IA (mean difference = 7.85°; 95% CI = 4.25° to 11.44°; p < 0.001). Other outcome variables were not significantly different among the 3 groups. The only complications were wound drainage (1 each in the IA and IA+PA groups) and deep venous thrombosis (1 in the IA group). Conclusions: PA was associated with less early postoperative pain and greater active knee flexion compared with the other 2 analgesic methods. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Ultrasound and nerve stimulator guidance lumbar transforaminal epidural block for the treatment of patients with lumbosacral radicular pain.

Transforaminal epidural block (TEB) is a widely accepted technique and minimally invasive procedure for the treatment of lumbosacral radicular pain. This study aimed to evaluate the accuracy, efficacy, and safety of ultrasound and nerve stimulator guidance lumbar transforaminal epidural block (UNTEB) for the patients with unilateral lower lumbar radicular pain. The accuracy of this method was evaluated by fluoroscopy. Using UNTEB via axial and the in-plane approach technique was performed in 42 segments of 25 patients who presented with lumbosacral radicular pain to lower extremities. The contrast medium was injected to evaluate the needle tip at the intervertebral foramen under fluoroscopic guidance. The numerical rating scale was used to assess pain before and after treatment. The success ratio of UNTEB in L3/L4 level was 100%, in L4/L5 was 95.4% and in L5/S1 was 100%. The numerical rating scale (NRS) for lumbosacral radicular pain improved from a mean from 7.8 to 2.8 1 day after procedure (p = 0.01) and from a mean from 7.8 to 2.4 1 week after UNTEB (p = 0.01). None of our subjects experienced any complications during and after the procedure. UNTEB with fluoroscopic validation is an accurate, effective, and safe method for short-term pain relief of the patients with unilateral lumbosacral radicular pain.

Ac-SDKP peptide improves functional recovery following spinal cord injury in a preclinical model.

Damage to the spinal cord triggers a local complex inflammatory reaction that results in irreversible impairments or complete loss of motor function. The evidence suggested that inhibiting the pro-inflammatory macrophage/microglia (M1 subsets) and stimulating the anti-inflammatory macrophage/microglia (M2 subsets) are potential strategies for the treatment of neuroinflammation-related diseases. We evaluated the potentially protective effect of Ac-SDKP as an endogenous tetrapeptide on rat spinal cord injury (SCI). Wistar rats were subjected to a weight-drop contusion model and were treated with Ac-SDKP (0.8 mg/kg) given subcutaneously once a day for 7 days starting at two clinically relevant times, at 2 h or 6 h post-injury. The effect of Ac-SDKP was assessed by motor functional analysis, real-time PCR (CD86 and CD206 mRNA), western blot (caspase-3), ELISA (TNF-a, IL-10), and histological analysis (toluidine blue staining). Ac-SDKP improved locomotor recovery and rescue motor neuron loss after SCI. Moreover, a decreased in TNF-a level as well as caspase 3 protein levels occurred in the lesion epicenter of the spinal cord following treatment. In addition, CD206 mRNA expression level increased significantly in Ac-SDKP treated rats compared with SCI. Together these data suggest that Ac-SDKP might be a novel immunomodulatory drug. It may be beneficial for the treatment of SCI with regards to increasing CD206 gene expression and suppress inflammatory cytokine to improve motor function and reducing histopathological lesion.

Low-dose whole-lung irradiation in severe COVID-19 pneumonia: a controlled clinical trial.

INTRODUCTION: The COVID-19 pandemic has caused significant morbidity and mortality thus far. Considering the historical uses of high-voltage X-ray beams for unresolvable pneumonia, we aimed to assess whether low-dose whole-lung irradiation (WLI) could provide any benefits for patients with refractory COVID-19 pneumonia. METHODS: Eleven patients with refractory COVID-19 pneumonia were treated with WLI to a total dose of 1 Gy and compared to 11 patients in a matched control group from June to November 2020. The study's primary endpoint was improvement of chest X-ray severity score (CXRS), followed by changes in mean oxygen (O2) saturation and 28-day mortality as secondary endpoints. RESULTS: The final CXRS was significantly lower in the WLI group (8.7 ± 2.5) compared to the control group (12.3 ± 3.3) (P: 0.016). Change of CXRS from the first to the last chest X-ray was -2.2 ± 3.1 for the WLI group and 0.7 ± 3.9 for the control group, which showed a trend for lower CXRS in the WLI group (U = 30, p: 0.085). Mean O2 saturation showed insignificant improvement in the first 24 hours after radiotherapy (mean difference: 2.5 ± 4.1, Z=-1.6, P value: 0.11). Overall survival after 28 days was 32% in the WLI group and 11% in the control group (P: 0.48). The reason for death in many patients was not merely respiratory failure, but also other adverse situations like pneumothorax, cardiogenic shock and pulmonary thromboembolism. CONCLUSIONS: Low-dose WLI could improve the CXR severity score and O2 saturation in severely ill COVID-19 patients, but larger studies are required to determine its impact on mortality.