Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans.

Post-traumatic stress disorder (PTSD) is one of the most widespread and disabling psychiatric disorders among combat veterans. Substantial interindividual variability in susceptibility to PTSD suggests the presence of different risk factors for this disorder. Twin and family studies confirm genetic factors as important risk factors for PTSD. In addition to genetic factors, epigenetic factors, especially DNA methylation, can be considered as a potential mechanism in changing the risk of PTSD. So far, many genetic and epigenetic association studies have been conducted in relation to PTSD. In genetic studies, many single nucleotide polymorphisms have been identified as PTSD risk factors. Meanwhile, the variations in catecholamines-related genes, serotonin transporter and receptors, brain-derived neurotrophic factor, inflammatory factors, and apolipoprotein E are the most prominent candidates. CpG methylation in the upstream regions of many genes is also considered a PTSD risk factor. Accurate identification of genetic and epigenetic changes associated with PTSD can lead to the presentation of suitable biomarkers for susceptible individuals to this disorder. This study aimed to delineate prominent genetic variations and epigenetic changes associated with post-traumatic stress disorder in military veterans who have experienced combat, focusing on genetic and epigenetic association studies.

Chronic Cinacalcet improves skin flap survival in rats: the suggested role of the nitric oxide pathway.

Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0.3, and 0.05 mg/kg) were used in 3 different routes of administration before the surgery. Histopathological evaluations, quantitative assessment of IL-6, TNF-α, and nitric oxide (NO), and the expression of calcium-sensing receptor (CaSR) and E-cadherin were evaluated in the skin tissue. To assess the role of NO, a NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME), was used, and histopathological effects were investigated. Cinacalcet pretreatment at the IP chronic 1 mg/kg dose significantly increased the skin flap survival rate and enhanced the NO tissue level compared to the control. However, the administration of L-NAME abolished its protective effects. IP Chronic 1 mg/kg of Cinacalcet could also decline the levels of IL-6 and TNF-α and also increase the expression of CaSR and E-cadherin in the flap tissue compared with the control group. Chronic Cinacalcet at 1 mg/kg could improve skin flap survival, probably mediated by the CaSR, NO, and inflammation-related pathways.

Cilostazol pretreatment prevents PTSD-related anxiety behavior through reduction of hippocampal neuroinflammation.

Current pharmacological treatments against post-traumatic stress disorder (PTSD) lack adequate efficacy. As a result, intense research has focused on identifying other molecular pathways mediating the pathogenesis of this condition. One such pathway is neuroinflammation, which has demonstrated a role in PTSD pathogenesis by causing synaptic dysfunction, neuronal death, and functional impairment in the hippocampus. Phosphodiesterase (PDE) inhibitors (PDEIs) have emerged as promising therapeutic agents against neuroinflammation in other neurological conditions. Furthermore, PDEIs have shown some promise in animal models of PTSD. However, the current model of PTSD pathogenesis, which is based on dysregulated fear learning, implies that PDE inhibition in neurons should enhance the acquisition of fear memory from the traumatic event. As a result, we hypothesized that PDEIs may improve PTSD symptoms through inhibiting neuroinflammation rather than long-term potentiation-related mechanisms. To this end, we tested the therapeutic efficacy of cilostazol, a selective inhibitor of PDE3, on PTSD-related anxiety symptoms in the underwater trauma model of PTSD. PDE3 is expressed much more richly in microglia and astrocytes compared to neurons in the murine brain. Furthermore, we used hippocampal indolamine 2,3-dioxygenase 1 (IDO) expression and interleukin 1 beta (IL-1ß) concentration as indicators of neuroinflammation. We observed that cilostazol pretreatment prevented the development of anxiety symptoms and the increase in hippocampal IDO and IL-1ß following PTSD induction. As a result, PDE3 inhibition ameliorated the neuroinflammatory processes involved in the development of PTSD symptoms. Therefore, cilostazol and other PDEIs may be promising candidates for further investigation as pharmacological therapies against PTSD.

Some relevant mitigating agents of chronic aflatoxin exposure: a treatise.

Aflatoxins, a group of toxic secondary metabolites produced by Aspergillus species, pose significant threats to human health due to their potent carcinogenic, mutagenic, and immunosuppressive properties. Chronic exposure to these contaminants, commonly found in staple foods such as maize and groundnuts, has been linked to an increased risk of liver cancer, growth impairment, and immune dysfunction. Several agents, such as calcium montmorillonite clay and Lactobacillus rhamnosus GG, have shown promise in reducing aflatoxin bioavailability and alleviating its toxic effects. Additionally, dietary supplements such as chlorophyllin, selenium, and N-acetylcysteine have demonstrated potential as adjuvants to counteract aflatoxin-induced oxidative stress and support liver function. In this treatise, some of the most discussed approaches to mitigating aflatoxin effects are explored in terms of their efficacy, safety, and potential mechanisms of action, which include direct aflatoxin binding, detoxification, cellular antioxidative, and hepatocellular protection properties. However, the effectiveness of these strategies can be influenced by various factors, such as dose, duration of exposure, and individual susceptibility. Therefore, further research is needed to optimize these interventions and develop new, targeted therapies for the prevention and treatment of aflatoxin-related diseases. This review aims to provide a comprehensive analysis of 18 pharmaceutical, nutraceutical, supplement, and probiotic strategies currently available for mitigating the deleterious effects of chronic aflatoxin exposure in humans and animal models.

Dexmedetomidine versus sufentanil as adjuvants to bupivacaine for brachial plexus block during upper extremity surgery: a randomized clinical trial

Abstract Background: Brachial plexus block (BPB) has been accepted as a reliable alternative for general anesthesia in upper limb surgeries. Adding adjuvant drugs like dexmedetomidine and sufentanil has been shown to have clinical and pharmacologic advantages. In this randomized parallel clinical trial, we aim to compare the effects of these two adjuvants for bupivacaine in BPB. Methods: In this double-blinded study, by using computer-assisted block randomization, 40 patients ranged from 20 to 65 years old and scheduled for elective upper limb surgeries were assigned to two equal study groups (n = 20), receiving 1 mL of 5 μg.mL-1 sufentanil (group S) or 1 mL of 100 μg.mL-1 dexmedetomidine (group D) in adjunction to 30 mL of 0.5% bupivacaine for supraclavicular BPB under the guidance of ultrasonography. Characteristics of local anesthesia and postoperative analgesia were evaluated (n = 40). Results: The duration of blocks significantly improved in group S (sensory: estimated median difference (EMD) [95%CI] = 100.0 [70.0~130.0], p < 0.001; motor: EMD [95%CI] = 120.0 [100.0~130.0], p < 0.001). Group S also had significantly longer postoperative analgesia and lower opioid consumption within 24 hours after the surgery (EMD [95%CI] = 4.0 [3.0~7.0], p < 0.001; EMD [95%CI] = -5.0 [-5.0~-5.0], p < 0.001; respectively). None of the patients showed adverse effects concerning vital signs, nausea, or vomiting. Conclusion: Our study showed that during ultrasound-guided supraclavicular BPB, sufentanil is a fairly better choice than dexmedetomidine as an adjuvant for bupivacaine and can provide preferable sensory and motor blocks. No significant side effects were seen in either of the study groups.

Inhibition of bacterial adhesion and anti-biofilm effects of Bacillus cereus and Serratia nematodiphila biosurfactants against Staphylococcus aureus and Pseudomonas aeruginosa.

Background and Objectives: Biosurfactants are amphiphilic surface-active agents that mainly produced by various microorganisms. In this study, the anti-biofilm and inhibition of bacterial adhesion activities of two bacterial biosurfactants were investigated. Materials and Methods: After extraction and evaluation of Bacillus cereus and Serratia nematodiphila biosurfctants, inhibition of bacterial adhesion and anti-biofilm effects of them on Staphylococcus aureus and Pseudomonas aeruginosa were determined. Results: On average, the synergistic effect of two bacterial biosurfactants, caused about 60% decrease in adhesion and about 80% decrease in biofilm formation of S. aureus and P. aeruginosa. Conclusion: The results of this study showed that combination of B. cereus and S. nematodiphila biosurfactants would increase the potential of attachment inhibition and biofilm eradication with very low toxicity.

Bipolar Androgen Therapy: When Excess Fuel Extinguishes the Fire.

Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through "Darwinian" treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.

Oleanolic acid increases the anticancer potency of doxorubicin in pancreatic cancer cells.

Combination therapy is a novel cancer therapy approach that combines two or more chemotherapy drugs. This treatment modality enhances the efficacy of chemotherapy by targeting key pathways in an additive or synergistic manner. Therefore, we investigated the efficacy of combination therapy by widely used chemotherapy drug doxorubicin (DOX) and oleanolic acid (OA) to induction of apoptosis for pancreatic cancer (PC) therapy. The effects of DOX, OA, and their combination (DOX-OA) were investigated on proliferation and viability of PC cell line (PANC-1) by MTT assay. Moreover, migration and invasion of the cancer cells were evaluated by trans-well migration assay and wound healing assay. Flow cytometry and DAPI (4',6-diamidino-2-phenylindole) staining were employed to investigate apoptosis quantification and qualification of the treated cancer cells. Finally, mRNA expression of apoptosis-related genes was assessed by quantitative real-time polymerase chain reaction. Our results demonstrated that the proliferation and metastasis potential of PC cells significantly decreased after treatment by DOX, OA, and DOX-OA. Moreover, we observed an increase in apoptosis percentage in the treated cancer cells. The apoptosis-related gene expression was modified to increase the apoptosis rate in all of the treatment groups. However, the anticancer potency of DOX-OA combination was significantly more than that of DOX and OA treatments alone. Our study suggested that DOX-OA combination exerts more profound anticancer effects against PC cell lines than DOX or OA monotherapy. This approach may increase the efficiency of chemotherapy and reduce unintended side effects by lowering the prescribed dose of DOX.

Phosphodiesterase inhibitors in psychiatric disorders.

RATIONALE: Challenges in drug development for psychiatric disorders have left much room for the introduction of novel treatments with better therapeutic efficacies and indices. As a result, intense research has focused on identifying new targets for developing such pharmacotherapies. One of these targets may be the phosphodiesterase (PDE) class of enzymes, which play important roles in intracellular signaling. Due to their critical roles in cellular pathways, these enzymes affect diverse neurobiological functions from learning and memory formation to neuroinflammation. OBJECTIVES: In this paper, we reviewed studies on the use of PDE inhibitors (PDEIs) in preclinical models and clinical trials of psychiatric disorders including depression, anxiety, schizophrenia, post-traumatic stress disorder (PTSD), bipolar disorder (BP), sexual dysfunction, and feeding disorders. RESULTS: PDEIs are able to improve symptoms of psychiatric disorders in preclinical models through activating the cAMP-PKA-CREB and cGMP-PKG pathways, attenuating neuroinflammation and oxidative stress, and stimulating neural plasticity. The most promising therapeutic candidates to emerge from these preclinical studies are PDE2 and PDE4 inhibitors for depression and anxiety and PDE1 and PDE10 inhibitors for schizophrenia. Furthermore, PDE3 and 4 inhibitors have shown promising results in clinical trials in patients with depression and schizophrenia. CONCLUSIONS: Larger and better designed clinical studies of PDEIs in schizophrenia, depression, and anxiety are warranted to facilitate their translation into the clinic. Regarding the other conditions discussed in this review (most notably PTSD and BP), better characterization of the effects of PDEIs in preclinical models is required before clinical studies.

Beneficial Effects of Statins on Seizures Independent of Their Lipid-Lowering Effect: A Narrative Review.

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin's mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders.

Dexmedetomidine versus sufentanil as adjuvants to bupivacaine for brachial plexus block during upper extremity surgery: a randomized clinical trial.

BACKGROUND: Brachial plexus block (BPB) has been accepted as a reliable alternative for general anesthesia in upper limb surgeries. Adding adjuvant drugs like dexmedetomidine and sufentanil has been shown to have clinical and pharmacologic advantages. In this randomized parallel clinical trial, we aim to compare the effects of these two adjuvants for bupivacaine in BPB. METHODS: In this double-blinded study, by using computer-assisted block randomization, 40 patients ranged from 20 to 65 years old and scheduled for elective upper limb surgeries were assigned to two equal study groups (n = 20), receiving 1 mL of 5 ..g.mL-1 sufentanil (group S) or 1 mL of 100 ..g.mL-1 dexmedetomidine (group D) in adjunction to 30 mL of 0.5% bupivacaine for supraclavicular BPB under the guidance of ultrasonography. Characteristics of local anesthesia and postoperative analgesia were evaluated (n = 40). RESULTS: The duration of blocks significantly improved in group S (sensory: estimated median difference (EMD) [95%CI] = 100.0 [70.0...130.0], p < 0.001; motor: EMD [95%CI] = 120.0 [100.0...130.0], p < 0.001). Group S also had significantly longer postoperative analgesia and lower opioid consumption within 24 hours after the surgery (EMD [95%CI] = 4.0 [3.0...7.0], p < 0.001; EMD [95%CI] = -5.0 [-5.0...-5.0], p < 0.001; respectively). None of the patients showed adverse effects concerning vital signs, nausea, or vomiting. CONCLUSION: Our study showed that during ultrasound-guided supraclavicular BPB, sufentanil is a fairly better choice than dexmedetomidine as an adjuvant for bupivacaine and can provide preferable sensory and motor blocks. No significant side effects were seen in either of the study groups.

Neuronal nitric oxide synthase inhibition accelerated the removal of fluoxetine's anxiogenic activity in an animal model of PTSD.

While SSRIs are the current first-line pharmacotherapies against post-traumatic stress disorder (PTSD), they suffer from delayed onset of efficacy and low remission rates. One solution is to combine SSRIs with other treatments. Neuronal nitric oxide synthase (nNOS) has been shown to play a role in serotonergic signaling, and there is evidence of synergism between nNOS modulation and SSRIs in models of other psychiatric conditions. Therefore, in this study, we combined subchronic fluoxetine (Flx) with 7-nitroindazole (NI), a selective nNOS inhibitor, and evaluated their efficacy against anxiety-related behavior in an animal model of PTSD. We used the underwater trauma model to induce PTSD in rats. Animals underwent the open field (OFT) and elevated plus maze tests on days 14 (baseline) and 21 (post-treatment) after PTSD induction to assess anxiety-related behaviors. Between the two tests, the rats received daily intraperitoneal injections of 10 mg/kg Flx or saline, and were injected intraperitoneally before the second test with either 15 mg/kg NI or saline. The change in behaviors between the two tests was compared between treatment groups. Individual treatment with both Flx and NI had anxiogenic effects in the OFT. These effects were associated with modest increases in cFOS expression in the hippocampus. Combination therapy with Flx + NI did not show any anxiogenic effects, while causing even higher expression levels of cFOS. In conclusion, addition of NI treatment to subchronic Flx therapy accelerated the abrogation of Flx's anxiogenic properties. Furthermore, hippocampal activity, as evidenced by cFOS expression, was biphasically related to anxiety-related behavior.

Evaluating the effects of zeolitic imidazolate framework and Eremostachys binalodensis extract on Candida albicans and Streptococcus mutans biofilms.

Biofilms represent longstanding challenges to oral health care. Candida albicans and Streptococcus mutans are the common pathogens forming biofilms. The growing resistance to and the adverse effects of antibiotics limit their usage and raise the need for novel approaches. Herbal extracts have emerged as efficient choices with lower costs and fewer adverse effects. Metal frameworks have captivated interest due to their high surface area, special biocompatibility, and non-toxicity. The effects of zeolitic imidazolate frameworks/layered double hydroxide (ZIF/LDH) on fungal infections and the potential effects of Eremostachys binalodensis on bacteria encouraged the researchers to evaluate the effect of ZIF/LDH, E. binalodensis, and their combination on C. albicans and S. mutans biofilms. ZIF/LDH nanocomposite was synthesized and characterized using scanning electron microscopy, Fourier transform infrared spectra, and X-ray diffraction to assess morphology and chemical structure. Methanol extracts of the areal parts of E. binalodensis were obtained by Soxhlet extraction. The microdilution tests and biofilm crystal violet staining were applied. Concentrations of 2.048 and 4.096 mg/ml E. binalodensis prevented C. albicans and S. mutans biofilm formation. The combination of ZIF/LDH + E. binalodensis prevented C. albicans and S. mutans biofilm formation. This research suggests the use of E. binalodensis-loaded ZIF/LDH nanocomposites for removing biofilms.

High-Intensity Interval Training-Induced Hippocampal Molecular Changes Associated with Improvement in Anxiety-like Behavior but Not Cognitive Function in Rats with Type 2 Diabetes.

(1) Background: Exercise exerts many neuroprotective effects in diabetes-induced brain disorders. In this study, we investigated the effect of high-intensity interval training (HIIT) on brain molecular changes and cognitive and anxiety-like behaviors in rats with type 2 diabetes. (2) Methods: Twenty-eight adult male rats were divided into four groups (n = 7): control (C), exercise + control (C+EX), diabetes (DM), and diabetes + exercise (DM+EX). Diabetes was induced using a two-month high-fat diet and a single dose of streptozotocin (35 mg/kg) in the DM and DM+EX groups. After, the C+EX and DM+EX groups performed HIIT for eight weeks (five sessions per week, running at 80-100% of VMax, 4-10 intervals) on a motorized treadmill. Then, the elevated plus maze (EPM) and open field test (OFT) were performed to evaluate anxiety-like behaviors. The Morris water maze (MWM) and shuttle box were used to assess cognitive function. The hippocampal levels of beta-amyloid and tau protein were also assessed using Western blot. (3) Results: The hippocampal levels of beta-amyloid and tau protein were increased in the DM group, but HIIT restored these changes. While diabetes led to a significant decrease in open arm time percentage (%OAT) and open arm enters percentage (%OAE) in the EPM, indicating anxiety-like behavior, HIIT restored them. In the OFT, grooming was decreased in diabetic rats, which was restored by HIIT. No significant difference between groups was seen in the latency time in the shuttle box or for learning and memory in the MWM. (4) Conclusions: HIIT-induced hippocampal molecular changes were associated with anxiety-like behavior improvement but not cognitive function in rats with type 2 diabetes.

Targeting neuronal nitric oxide synthase and the nitrergic system in post-traumatic stress disorder.

RATIONALE: Current pharmacological approaches to treatment of post-traumatic stress disorder (PTSD) lack adequate effectiveness. As a result, identifying new molecular targets for drug development is necessary. Furthermore, fear learning and memory in PTSD can undergo different phases, such as fear acquisition, consolidation, and extinction. Each phase may involve different cellular pathways and brain regions. As a result, effective management of PTSD requires mindfulness of the timing of drug administration. One of the molecular targets currently under intense investigation is the N-methyl-D-aspartate (NMDA)-type glutamate receptor (NMDAR). However, despite the therapeutic efficacy of drugs targeting NMDAR, their translation into clinical use has been challenging due to their various side effects. One possible solution to this problem is to target signaling proteins downstream to NMDAR to improve targeting specificity. One of these proteins is the neuronal nitric oxide synthase (nNOS), which is activated following calcium influx through the NMDAR. OBJECTIVE: In this paper, we review the literature on the pharmacological modulation of nNOS in animal models of PTSD to evaluate its therapeutic potential. Furthermore, we attempt to decipher the inconsistencies observed between the findings of these studies based on the specific phase of fear learning which they had targeted. RESULTS: Inhibition of nNOS may inhibit fear acquisition and recall, while not having a significant effect on fear consolidation and extinction. However, it may improve extinction consolidation or reconsolidation blockade. CONCLUSIONS: Modulation of nNOS has therapeutic potential against PTSD and warrants further development for use in the clinical setting.

Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: A double-blind placebo-controlled clinical trial.

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration (p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group (p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.

Association of a miRNA-binding site polymorphism in IL-16 gene with disease risk and clinical characteristics of rheumatoid arthritis and systemic lupus erythematosus.

INTRODUCTION: /objectives. Single nucleotide polymorphisms (SNPs) located at the 3'-UTR region of the target genes of microRNAs (miRNAs) can dysregulate their expression via disrupting the binding site of miRNAs. Interleukin-16 (IL-16) is involved in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In the current study, we assessed the possible association between rs1131445 polymorphism in IL-16 gene with risk and clinical characteristics of RA and SLE in the Iranian population. METHODS: In this case-control study, 120 patients with RA, 120 patients with SLE, and 120 unrelated healthy subjects were collected to estimate rs1131445 (T > C) polymorphism in IL-16 gene using real-time PCR high-resolution melting (HRM) method. RESULTS: Our results demonstrated considerable associations between TC genotype and C allele of rs1131445 with enhanced risk of RA (ORfor TC genotype = 3.01; 95%CI [1.667-5.526], P < 0.001; ORfor C allele = 1.96; 95%CI [1.314-2.941], P < 0.001). Besides, there was a marginal association between CC genotype and increased risk of RA (P: 0.031). However, there was an insignificant correlation between genotypes and allele frequencies of rs1131445 with incidence risk of SLE (P > 0.05). Moreover, stratification analysis indicated that the C allele in rs1131445 was linked with disease activity-associated laboratory parameters such as CRP and ESR in both RA and SLE patients, as well as the higher incidence of neurological symptoms in SLE subjects (P < 0.05). CONCLUSION: These results proposed a significant association between IL-16 polymorphism and augmented risk of RA and clinical characteristics of RA and SLE.

Sub-Flap Use of Nano-Selenium Oxide Solution Enhances Skin Flap Viability in Rats: Study the Novel Role of mTOR and p-mTOR Expression.

BACKGROUND: Nano-selenium oxide (NSeO) particles are highly noticeable due to their tissue-protective and antioxidant properties. For this purpose, the effect of NSeO was evaluated on skin flap survival and flap oxidative stress markers in rats. Also, another effect of NSeO was investigated on the expression of mTOR and p-mTOR. MATERIALS AND METHODS: Fifty rats were divided into five groups of ten. Skin flap size was 3×8 cm in all groups. Groups were: (1) Sham, (2) Flap Surgery group, (3) Flap Surgery + NSeO, (4) Flap Surgery + Rapamycin (mTOR inhibitor), (5) Flap Surgery + Rapamycin + NSeO. The flap necrosis rate was computed using the paper pattern method on day seven after surgery. After day seven, flap tissues were collected for histological evaluations. Then, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Furthermore, the expression levels of mTOR and p-mTOR were measured using the Western blot method. RESULTS: Treatment with NSeO significantly reduced necrosis (P<0.05). It also resulted in a decrease in MDA level (P<0.05). Histologically, NSeO reduced inflammation and increased positive signs of tissue healing (epithelialization, neovascularization, fibroblast migration, and granulation tissue). NSeO increased SOD activity significantly (P<0.05), whereas, using rapamycin reversed these effects. Also, in all groups, mTOR changes were not significant. Additionally, p-mTOR expression was significantly reduced in groups that rapamycin was injected. CONCLUSION: NSeO can reduce flap necrosis and enhance tissue healing in rats. So, it can potentially be used clinically to promote tissue repair significantly, and its effects are independent of the mTOR pathway. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Pharmacological evidence for the possible involvement of the NMDA receptor pathway in the anticonvulsant effect of tramadol in mice.

Background: Previous studies have shown controversial results regarding the pro- or anticonvulsant effects of tramadol. Additionally, the underlying mechanism of seizure induction or alleviation by tramadol has not been fully understood. In the current study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizure and the possible involvement of the N-methyl-D-aspartate (NMDA) pathway were assessed in mice. Methods: Male Naval Medical Research Institute (NMRI) mice were treated with intravenous infusion of PTZ in order to induce clonic seizures and determine seizure threshold. Tramadol was injected intraperitoneally (0.1-150 mg/kg) 30 minutes prior to elicitation of seizures. The possible effects of intraperitoneal injections of NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.5 mg/kg) on the anticonvulsant property of tramadol were investigated subsequently. Results: Tramadol (1-100 mg/kg) increased PTZ-induced seizure threshold in a dose-dependent, time-independent manner, with optimal anticonvulsant effect at a dose of 100 mg/kg. Acute administration of either ketamine (0.5 mg/kg) or MK-801 (0.5 mg/kg) potentiated the anticonvulsant effect of a subeffective dose of tramadol (0.3 mg/kg). Conclusion: These results suggest a possible role of the NMDA pathway in the anticonvulsant effect of tramadol.

Effect of Dexmedetomidine infusion during hip fracture surgery on hemodynamic parameters and blood loss: A triple-blinded Randomized Clinical Trial.

Introduction In this study, we aim to assess the intra-operative effect of dexmedetomidine administration on the hemodynamic parameters and bleeding volume during hip fracture surgery. Patients and methods we designed and implemented a triple-blinded randomized clinical trial to objectively compare the effects of 0.5 µg/kg/h infusion of dexmedetomidine with placebo (equal amount of normal saline) during hip fracture surgery. All included cases were between 30 and 70 years old and underwent surgery for fixation of a proximal femur fracture from September 26, 2020 until February 15, 2021. They were all ASA class I or II with preoperative hemoglobin levels of 10 mg/dL or higher. Surgical blood loss and hemodynamic parameters were documented. Results 76 patients were enrolled. There were no significant differences in baseline patient characteristics. The bleeding rate was 620 ± 190.0 mL for the normal saline group and 476 ± 177.98 mL in the dexmedetomidine group (P = 0.04). No significant effect on hemodynamic parameters was observed. Conclusion Based on the current study, intravenous infusion of dexmedetomidine during hip fracture surgery under general anesthesia reduced the amount of intraoperative bleeding without causing any significant hemodynamic disturbances. Registration number IRCT20191222045857N1 (Iranian Registry of Clinical Trials).