Comparison of the Effects of Plasmapheresis, Hemoperfusion, and Convalescent Plasma Therapy on Inflammatory Factors in COVID-19 Patients.

Background: Since the emergence of coronavirus disease 2019 (COVID-19), the treatment protocols are continuously updated, based on the evidence gathered all around the world and reported to the World Health Organization. Like many other emerging infectious diseases, using convalescent plasma from those recovered from the disease was a preliminary treatment approach that showed partial effectiveness for severe COVID-19 patients. Besides, blood filtration strategies, such as hemoperfusion and plasmapheresis, are employed to lessen the load of inflammatory molecules. However, few studies compared their effects to conclude which treatment might be more efficacious for COVID-19 patients. We compared the effects of plasmapheresis or plasma exchange, convalescent plasma therapy, and hemoperfusion on O2 saturation and inflammatory factors in COVID-19 patients. Methods: In this retrospective study, 50 COVID-19 patients received standard treatments based the international guidelines. Patients were divided into 4 groups: hemoperfusion, plasmapheresis, plasma therapy, and control. The control group received only the standard treatments. The mortality rate, O2 saturation, and laboratory factors were compared between the 4 groups. Results: We found a significant decrease in the C-reactive protein level following hemoperfusion (32.75 ± 23.76 vs 13 ± 7.54 mg/dL; p = 0.032) but not plasmapheresis and plasma therapy. Besides, serum levels of lactate dehydrogenase (p = 0.327, 0.136, 0.550, for hemoperfusion, plasmapheresis, and plasma therapy, respectively) and other inflammatory molecules did not significantly change following treatments. There is also no significant difference in the mortality rate between the treatment groups (p = 0.353). Conclusion: It seems that hemoperfusion, plasmapheresis, and plasma therapy did not have considerable effects on decreasing the inflammation and mortality rate compared with standard treatment.

Continuous Renal Replacement Therapy with Low Dose Systemic Heparin in Liver Transplant Recipients.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is an effective dialysis method in critically ill patients. Citrate and heparin are commonly used as anticoagulants to prevent premature circuit clotting. The aim of this study was to evaluate the safety and efficacy of using low dose systemic heparin while on CRRT in liver transplant recipients. METHODS: We retrospectively evaluated and analyzed data from 29 liver transplant recipients undergoing CRRT in the postoperative course in this cross-sectional study. Numerous variables were recorded, such as coagulation parameters, duration of intensive care unit (ICU) stay, duration of dialysis, heparin dose, circuit life span, and anticoagulant complications. RESULTS: Out of 29 recipients, there were 16 (55%) female and 13 (45%) male. All participants underwent whole organ liver transplantation with a median age of 45 years. Overall, 98 successful dialysis sessions were recorded in this study with a mean circuit life span of 36 hours. Mean ± SD duration of CRRT for each recipient was 4.8 ± 3.1 days. The median total dose of heparin used for each recipient was 25,000 units , and the median dose of heparin per-day for each recipient was about 3,300 units. There were no episodes of anticoagulant-related bleeding complications. Thirteen (13.2%) episodes of premature circuit clotting occurred. We found a significant association between the first dose and total dose of heparin usage with first postoperative INR and PTT level (P < .05, P < .05, P < .001, and P < .05). CONCLUSION: In liver transplant recipients, low dose heparin during CRRT for patency of circuit is well tolerated.

Simvastatin prevents morphine antinociceptive tolerance and withdrawal symptoms in rats.

BACKGROUND/PURPOSE: Long-term exposure to opiates induces tolerance to the analgesic effect and dependence. In recent years, several studies have been conducted to find agents that can prevent the development of these two phenomena. The aim of the present study is to evaluate the effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on morphine-induced tolerance and withdrawal symptoms. METHODS: Groups of male rats received daily morphine [for induction of tolerance (10 mg/kg) and for induction of dependence (additive doses: 5 mg/kg/12 h, 10 mg/kg/12 h, 15 mg/kg/12 h, 20 mg/kg/12 h, and 25 mg/kg/12 h)] in combination with propylene glycol or simvastatin [5 mg/kg, per os (p.o.), 10 mg/kg, p.o., and 20 mg/kg, p.o.]. Next, the nociception was assessed by the plantar test apparatus. The latency was recorded when the animal responded to the light stimulus. The animals received additional doses of morphine for 9 days in order to induce dependency. One hour after the last dose of the morphine injection, naloxone was administered and withdrawal symptoms were recorded for 1 hour. RESULTS: The results of the present study showed that chronic morphine administration induced tolerance to the analgesic effect for 19 days, whereas simvastatin (20 mg/kg, p.o.) delayed the day of the established tolerance by 5 days. The administration of simvastatin also prevented the morphine-induced shift to the right of the 50% effective dose (ED50) in the dose-response curve. Furthermore, the results showed that simvastatin decreased the total withdrawal score significantly. CONCLUSION: We found that simvastatin attenuated morphine-induced tolerance and withdrawal symptoms.

Pioglitazone prevents morphine antinociceptive tolerance via ameliorating neuroinflammation in rat cerebral cortex.

BACKGROUND: Opioid induced neuroinflammation is shown to be implicated in opioid analgesic tolerance development. In the present study the effect of pioglitazone on morphine-induced tolerance and neuroinflammation in the cerebral cortex of the rat was investigated. MATERIALS AND METHODS: Various groups of rats received morphine (10mg/kg; ip) and vehicle (po), or morphine (10mg/kg) and pioglitazone (20 or 40 mg/kg; po) once a day for 17 days. In order to determine the possible involvement of PPAR-γ in the pioglitazone effect, one group of rats received PPAR-γ antagonist, GW-9662 (2mg/kg; sc), and pioglitazone (40 mg/kg) and morphine once daily for 17 days. Nociception was assessed using a tail flick apparatus and the percentage of the maximal possible effect was calculated as well. On 18th day, 2h after the last morphine injection, the cerebral cortex of the animals were harvested and the tissue levels of tumour necrosis factor alpha, interleukin-1beta, interleukin-6, interleukin-10 and nuclear factor-kappa B activity were determined. RESULTS: Co-administration of pioglitazone (40 mg/kg) with morphine not only attenuated morphine-induced tolerance, but also prevented the up-regulation of pro-inflammatory cytokines (tumour necrosis factor alpha, interleukin-1beta, interleukin-6) and nuclear factor-kappa B activity in the rat cerebral cortex. Moreover, GW-9662 (2mg/kg) administration 30 min before pioglitazone, antagonized the above mentioned pioglitazone-induced effects. CONCLUSION: It is concluded that oral administration of pioglitazone attenuates morphine-induced tolerance. This effect of pioglitazone may be, at least in part, due to its anti-inflammatory property which suppressed the cortical pro-inflammatory cytokine and inhibited of nuclear factor-kappa B activity.

The role of structural C--H compared with phenolic OH sites on the antioxidant activity of oleuropein and its derivatives as a great non-flavonoid family of the olive components: a DFT study.

Oleuropein and its derivatives are the main phenolic compounds of Olea europaea L. leaf and fruit. The structure-antioxidant activity relationship was considered for studying the radical scavenging activity of this non-flavonoid family of the olive components using density functional theory (DFT). The structure of these compounds were optimized employing the B3LYP/6-31G (d,p) and the role of some structural CH positions was compared with phenolic OH sites on radical scavenging. As a result, a radical unique position (C3) in the oleuropein, characterized by low BDE (Bond Dissociation Enthalpy), reasonable spin density and electron distribution, was identified. The experimental results of the previous publications of oleuropein for NO and OH scavenging confirmed the presence of this unique active site in its molecular structure. According to the results, 2,2-diphenylpicrylhydrazyl (DPPH) cannot find this non-marginal active site. Therefore, DPPH may not be a determinant assay for all antioxidant comparisons. Solvent effects were considered in all calculations using a Polarized Continuum Model (PCM) at the B3LYP/6-31G (d,p) level. Solvation calculations were carried out for benzene (ε=2.3) to simulate the oil environment compared to gas phase.

A new pharmacological role for donepezil: attenuation of morphine-induced tolerance and apoptosis in rat central nervous system.

BACKGROUND: Tolerance to the analgesic effect of opioids is a pharmacological phenomenon that occurs after their prolonged administration. It has been shown that morphine-induced tolerance is associated with apoptosis in the central nervous system and neuroprotective agents which prevented apoptosis signaling could attenuate tolerance to the analgesic effects. On the other hand donepezil, an acetylcholinesterase inhibitor, has been reported to have neuroprotective effects. Therefore in this study, the effect of systemic administration of donepezil on morphine-induced tolerance and apoptosis in the rat cerebral cortex and lumbar spinal cord was evaluated. Various groups of rats received morphine (ip) and different doses of donepezil (0, 0.5, 1, 1.5 mg/kg/day). Nociception was assessed using tail flick apparatus. Tail flick latency was recorded when the rat shook its tail. For apoptosis assay other groups of rats received the above treatment and apoptosis was evaluated by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. RESULTS: The results showed that administration of donepezil (0.5, 1, 1.5 mg/kg, ip) delayed the morphine tolerance for 9, 12 and 17 days, respectively. Furthermore pretreatment injection of donepezil attenuated the number of apoptotic cells in the cerebral cortex and lumbar spinal cord compared to the control group. CONCLUSION: In conclusion, we found that systemic administration of donepezil attenuated morphine-induced tolerance and apoptosis in the rat cerebral cortex and lumbar spinal cord.