Effect of intravenous immunoglobulin on the management of Rh- and ABO-mediated hemolytic disease of the newborn.

BACKGROUND: Regarding the close association between neonatal hyperbilirubinemia and occurrence of pathological jaundice as a cause of neurotoxicity and kernicterus, the present study aimed to evaluate the use of intravenous immunoglobulin (IVIG) in neonates with hyperbilirubinemia. METHODS: A retrospective case-control study of blood group O mothers and their ABO and Rh newborns was conducted. Medical records that included total serum bilirubin levels of 79 patients with hemolytic disease of the newborn (HDN) from between 2017 and 2020 were reviewed. Neonates who were eligible to receive immunoglobulin based on the American Academy of Pediatrics (AAP) guidelines were classified as cases and the rest were included as the Control Group. RESULTS: The mean total bilirubin in relation to hemoglobin levels in IVIG-treated neonates was significantly lower than in non-IVIG-treated neonates (13.98 ± 4.23 mg/dL versus 16.61 ± 2.68 mg/dL; p-value = 0.002). Although females had longer hospitalizations in both IVIG-treated (3.81 ± 1.28 versus 3.54 ± 1.30 days; p-value = 0.509) and non-IVIG-treated (3.43 ± 0.811 versus 3.19 ± 0.75 days; p-value = 0.361) groups compared to males, this difference was not significant between the groups. Although four neonates with ABO incompatibility required packed red blood cells, all infants were managed medically and no deaths occurred during the course of treatment. Moreover, no exchange transfusion or adverse effects of IVIG were observed. CONCLUSION: The results from the present study revealed that IVIG administration is a useful procedure for the management of bilirubin encephalopathy with greater opportunity to reduce exchange transfusion requirements for neonatal hyperbilirubinemia.

The Repression of Matrix Metalloproteinases and Cytokine Secretion in Glioblastoma by Targeting K+ Channel.

Introduction: Glioblastoma is an aggressive human brain malignancy with poorly understood pathogenesis. Voltage-gated potassium (Kv) channels and Matrix Metalloproteinases (MMPs) are highly expressed in malignant tumors and involved in the progression and metastasis of glioblastoma. This study aimed to determine whether a voltage-dependent potassium channel blocker could modulate astrocytes as a cell involved in the immunopathogenesis of glioblastoma. Methods: The cytotoxic effect of 4-Aminopyridine (4-AP) at different doses in the cell model of glioblastoma was measured by MTT assay. The ELISA technique and gelatin zymography were used to assess cytokine levels and MMP-9 after 4-AP treatment. Results: Cytotoxicity analysis data indicated that cell viability reduced by increasing 4-AP level and cell growth decreased gradually by removing 4-AP from the cell medium. 4-AP inhibits the secretion of IL-6 and IL-1 (P<0.05). MMP9 activity significantly inhibits with increased 4-AP dose, compared to non-treated cells. Conclusion: The reduction of cell viability, IL-6 secretion, and MMP-9 activity in an in vitro model of glioblastoma might be assumed 4-AP as an agent for chemoprevention of cancer. Highlights: 4-Aminopyridine, as a K channel blocker, inhibits the secretion of IL-1.A voltage-gated potassium channel inhibits the secretion of IL-6.MMP9 activity, as a tumor metastasis marker, significantly decreased by 4-AP. Plain Language Summary: Glioblastoma is the most common primary malignant of the brain, which remains mainly untreatable. A group of enzymes -matrix metalloproteinases- can digest various extracellular matrix macromolecules. They express at a high level and play a role in the glioblastoma invasion. Besides, several substances are secreted by multiple cells and affect cancer metastasis. Among them, cytokines, like interleukin-6, released from glial cells, may contribute to glioblastoma progression. The present study determined whether an agent as a potassium channel blocker could modulate the immunopathogenesis of glioblastoma. We realized the cytotoxic effect of potassium channel blocker at different doses in the U-373 MG glioblastoma astrocytoma cells. Our chosen agent inhibits the secretion of both interleukin and matrix metalloproteinases activity. Overall, we suggest potassium channel blocker as an agent for cancer chemoprevention.

Augmented cAMP Signaling by Co-Administration of Resveratrol and Curcumin: A Cellular Biosensor Kinetic Assessment.

BACKGROUND: Curcumin and resveratrol are two polyphenolic compounds extensively investigated for their medicinal effects on inflammatory signaling. However, there is a paucity of information on the Adenosine-3', 5'-cyclic monophosphate (cAMP) kinetics following administration of curcumin and resveratrol in biological systems. In this study, kinetic modulation of cAMP as a target detection messenger in pro-inflammatory pathways was assessed by co-administration of curcumin and resveratrol using a cellular sensor model. METHODS: To evaluate their putative activity, curcumin and resveratrol compounds were administered alone or in combination on the media culture of cAMP EPAC (exchange protein directly activated by cAMP) bioluminescence resonance energy transfer (BRET) biosensor. The study was performed at the following two centers at Tehran University of Medical Sciences (TUMS): 1- Biotechnology Research Center, and, 2- Endocrinology and Metabolism Research Institute (EMRI) in 2017. Time course kinetic of cAMP response signals were plotted. Forskolin and IBMX were used to stabilize the cAMP signals. RESULTS: When we treated HEK-293T biosensor cells at 10uM concentration, curcumin and resveratrol upregulated cAMP signaling. Co-administration of resveratrol and curcumin revealed an augmented cAMP level, as compared to treatments with the compounds alone. CONCLUSION: Co-administration of curcumin and resveratrol leverage cAMP kinetic response in a time-course manner. The presented methodology can be readily adopted for drug development and novel biopharmaceutical functional analyses.

The influence of lateral and supine position on bacterial colonization of endotracheal tube in neonates admitted to neonatal intensive care unit.

OBJECTIVE: Recent data suggest that during mechanical ventilation, lateral patient position (in which the endotracheal tube is horizontal) decreases the incidence of bacterial colonization of ventilated neonates. The objective of this study was to evaluate the influence of lateral and supine position on bacterial colonization of endotracheal tube in neonates. METHODS: We conducted a prospective, randomized, clinical trial with 31 intubated neonates (intubated within 48 hours after birth); sixteen neonates were positioned supine (supine group), and fifteen were maintained in the lateral position (lateral group).Tracheal aspirates were cultured in second and fifth days of mechanical ventilation. Data were analyzed with SPSS version 16. FINDINGS: In the second day of ventilation, positive cultures were recognized in 6.2% of supine group and 6.7% of lateral group. After 5 days, tracheal cultures were positive in 25% (4 neonates) of supine group and 13.3% (2 neonates) of lateral group that wasn't statistically significant (P=0.9 in second day and P=0.9 in the fifth day). The most common organisms isolated from tracheal aspirates were Gram-negative rods (Klebsiella). CONCLUSION: Since respiratory contamination is very common among ventilated neonates and the effect of lateral position on bacterial colonization of endotracheal tubes of intubated neonates wasn't established in our study, further studies are required to suggest ways to decrease bacterial colonization of intubated neonates.