Effect of Lenalidomide on Pentylenetetrazole-Induced Clonic Seizure Threshold in Mice: A Role for N-Methyl-D-Aspartic Acid Receptor/Nitric Oxide Pathway

Background and Purpose: Accumulating evidence suggest that lenalidomide, a structural analog of thalidomide, has neuro-modulatory and neuroprotective properties. In the present study, we investigated effects of acute administration of lenalidomide on clonic seizure threshold in mice induced by pentylenetetrazole (PTZ) and possible role of N-methyl-D-aspartic acid receptor (NMDAR) and nitric oxide (NO) pathway. Methods: We have utilized a clonic model of seizure in NMRI mice induced by PTZ to evaluate the potential effect of lenalidomide on seizure threshold. Different doses of lenalidomide (5, 10, 20, and 50 mg/kg, intraperitoneal [i.p.]) were administered 1 hour before PTZ. To evaluate probable role of NMDAR/NO signaling, the non-selective NO synthase inhibitor L-N (G)-nitroarginine methyl ester (L-NAME; 10 mg/kg, i.p.), neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI; 30 mg/kg, i.p.), selective inducible NOS inhibitor aminoguanidine (AG; 100 mg/kg, i.p.), selective NMDAR antagonist MK-801 (0.01 mg/kg, i.p.), and selective NMDAR agonist D-serine (30 mg/kg, i.p.) were injected 15 minutes before lenalidomide. Results: Lenalidomide at 10 and 20 mg/kg significantly elevated the PTZ-induced seizure thresholds. Interestingly, L-NAME (10 mg/kg, i.p), 7-NI (30 mg/kg, i.p), and AG (100 mg/kg, i.p) reversed the anticonvulsive effect of lenalidomide (10 mg/kg). Moreover, treatment with the NMDAR agonist D-serine (30 mg/kg, i.p.) did not alter the anticonvulsive properties of lenalidomide (10 mg/kg, i.p). However, the NMDAR antagonist MK-801 (0.01 mg/kg, i.p) significantly reversed the anticonvulsive effects of lenalidomide (10 mg/kg). Conclusions: Our study demonstrated a role for the NMDAR/NO pathway in the anticonvulsive effects of lenalidomide on the PTZ-induced clonic seizures in mice

Isolated severe thrombocytopenia in a patient with COVID-19: A case report

COVID-19 is known to cause serious respiratory symptoms and involvement of other body systems such as hematopoietic, neurological and the immune system. In this report, we described a case of a COVID-19 patient who presented with no pulmonary involvement but severe thrombocytopenia. She suffered from headache and malaise with no respiratory symptoms, fever or chills. Chest radiological imaging was unremarkable but, the laboratory results showed significant thrombocytopenia associated with relatively decreased lymphocytes. Based on her high-risk work environment, a reverse transcription polymerase chain reaction (RT-PCR) test was performed and SARS-CoV-2 RNA was detected in the nasopharyngeal swab. Complete blood count (CBC) of patient was re-checked during admission and platelet count showed rising trend up to normal levels. A narrow diagnostic approach where only febrile patients with pulmonary symptoms are evaluated for a COVID-19 diagnosis will result in many missed diagnoses; so it is important that physicians are familiar with atypical and rare presentations of COVID-19, such as isolated thrombocytopenia

Predicting etCO2 response in a model of ventilation-perfusion mismatch

BACKGROUND:Aluminum phosphide (AlP) is used as pesticide in some countries for protection of stored grains. Human poisoning with AlP due to suicide attempt or accidental environmental exposure is associated with very high mortality partially due to development of severe metabolic acidosis. Previous studies have shown that hemoglobin has high buffering capacity and erythrocytes can potentially be used for management of metabolic acidosis. The aim of this study was to evaluate the effect of fresh packed red blood cells (RBC) transfusion on survival and cardiovascular function in AlP-poisoned rats. METHODOLOGY/PRINCIPAL FINDINGS:Rats were poisoned with AlP by gavage. Fresh packed RBC was transfused via tail vein after AlP administration. Acid-base balance, vital signs and mortality was assessed and compared in experimental groups. Infusion of fresh packed RBC (1.5 ml) one hour after AlP (4-15 mg/kg) intoxication was associated with a significant decrease in mortality rate. Packed RBC infusion improved blood pH, HCO3-, Na+ and Ca2+ levels. Plasma troponin level was also reduced and ECG changes were reversed following packed RBC infusion in AlP intoxicated rats. CONCLUSIONS:Our results showed that fresh RBC transfusion could ameliorate metabolic acidosis and enhance survival in AlP-poisoned rat. We assume that an increase in pool of RBCs may modulate acid-base balance or potentially chelate AlP-related toxic intermediates via phosphine-hemoglobin interaction

Kaplan-Meier graph showing the survival rate of rats intoxicated with different doses of oral aluminum phosphide (AlP) within 24 hours.

<p>Kaplan-Meier graph showing the survival rate of rats intoxicated with different doses of oral aluminum phosphide (AlP) within 24 hours.</p

Effects of fresh packed red blood cells (RBC) on blood pH, P_CO2, plasma electrolytes and troponin I.

<p>Values are expressed as mean ± S.E.M.</p

Effects of transfusions of fresh packed red blood cells (RBC) on mortality rate of aluminum phosphide (AlP)-poisoned rats.

<p>Packed RBC (1.5 ml) was infused 30, 60, 90 and 120 min after oral administration of AlP (12 mg/kg) and the mortality rate was assessed within 4 hours. * P<0.05, **** P<0.001 compared to saline-treated group.</p

Effects of transfusions of fresh packed red blood cells (RBC) on heart rate (HR), and ECG parameters in three experimental groups.

<p>Effects of transfusions of fresh packed red blood cells (RBC) on heart rate (HR), and ECG parameters in three experimental groups.</p

Effects of transfusions of different volumes of fresh packed red blood cells (RBC) on mortality rate of aluminum phosphide (AlP)-poisoned rats.

<p>Packed RBC suspensions (0.5, 1 and 1.5 ml) were infused 60 min after oral administration of AlP (12 mg/kg) and the mortality rate was assessed within 4 hours. * P<0.05, ** P<0.01, *** P<0.001 compared to saline-treated group.</p

Dose-dependent motility curves for the toxic effect of aluminum phosphide (AlP) in rats with or without transfusion of packed red blood cells (RBC).

<p>Packed RBC (1.5 ml) was infused one hour after oral administration of different doses of AlP.</p