Dextromethorphan attenuates ethanol withdrawal syndrome in rats

The effects of dextromethorphan (DM), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, have been investigated on ethanol withdrawal signs in rats. Ethanol (7.2% v/v) was given to rats in a liquid diet for 16 days. DM (10, 20, and 40 mg/kg) and saline were injected intraperitoneally at the third hour of ethanol withdrawal. DM (40 mg/kg) and ethanol dependent saline were also administered to ethanol naive rats. DM (40 mg/kg) did not produce any significant change in locomotor activity in ethanol naive rats. The effects of DM on locomotor activity and total ethanol withdrawal score were evaluated at the fourth and sixth hours of ethanol withdrawal. DM inhibited locomotor hyperactivity at these periods. DM also reduced total ethanol withdrawal score from the fourth hour to the sixth hour, and it significantly decreased audiogenic seizures. Seizure susceptibility after chronic ethanol exposure may be dependent upon sensitization or upregulation of NMDA processes and NMDA receptors. Our results suggest that inhibition of NMDA receptors by DM alleviates signs of ethanol withdrawal.     

Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes

Journal of Clinical Immunology - Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various...     

Prevalence of Occult Hepatitis B and Hepatitis C Virus Infections in Turkish Hemodialysis Patients

Background and Objective. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes of morbidity and mortality in maintenance hemodialysis patients. Although their exact prevalence is not known, HBV and HCV viral infections and occult viral hepatitis are frequent in these patients. This study aimed to determine the prevalence of occult HBV and HCV infections in maintenance hemodialysis patients. Materials and Methods. One hundred and eighty-eight end-stage renal disease patients on maintenance hemodialysis (100 male, mean age 49±29 [16–80] years, and mean duration of hemodialysis 98±66 [12–228] months) were enrolled in this study. Serological markers for HBV and HCV were determined with immunoenzymatic assay (ELISA) by using commercial diagnostic kits (Access and BioRad, Beckman-Coulter). HCV-RNA (Cobas Amplicor HCV kit) and HBV-DNA (Artus GmbH HBV kit) were determined quantitatively by polymerase chain reaction. Results. Among the patients screened, 25 (13.3%) had HBV infection alone and 38 (20.2%) had HCV infection alone, while seven (3.7%) had dual infection of both viruses. Serological markers for occult hepatitis B and occult hepatitis C were positive in five (2.7%) and nine (4.8%) of the patients, respectively. Isolated anti-HBc was positive in 12 (6.4%) of all patients, three (7.9%) of the patients with anti-HCV and two (40%) of the patients with occult hepatitis B. Isolated anti-HBc positivity was more frequent in patients with occult hepatitis B than in those without (40% [2/5] vs. 5.5% [10/183], p=0.002). None of the patients with HCV had occult hepatitis B. Conclusions. Both occult and non-occult forms of HCV infection are more prevalent than HBV infection in hemodialysis patients. Especially the patients with isolated anti-HBc positivity should be tested for probable occult hepatitis B infection.     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).     

A massive hiatal hernia that mimics a congenital diaphragmatic hernia. An unusual presentation of hiatal hernia in childhood: report of a case

A massive hiatal hernia containing the colon, intestine, and stomach with organoaxial volvulus is an uncommon entity in childhood. This clinical form of a hiatal hernia may mimic congenital diaphragmatic hernia and chest pathologies. In this paper, we describe a patient who presented with a massive hiatal hernia that mimicked a congenital diaphragmatic hernia, and discuss the pitfalls in diagnosing this clinical entity.     

Randomized,double-blinded,placebo-controlled trial of early administration of recombinant human granulocyte colony-stimulating factor to non-neutropenic preterm newborns between 33 and 36 weeks with presumed sepsis

A randomized, double-blinded, placebo-controlled trial was conducted of early administration of recombinant granulocyte colony-stimulating factor (rGCSF) to 40 non-neutropenic, preterm infants between 33 and 36 weeks of gestational age with the diagnosis of presumed sepsis. The treatment group (n = 20) received 5 microg/kg per day of intravenous rGCSF once daily for 3 d and the control group (n = 20) received the same volume of physiological serum. Immediately before the first dose and on the 4th day, plasma levels of GCSF and tumour necrosis factor-alpha (TNF-alpha), absolute neutrophil counts (ANC), immature neutrophil count (INC), immature/total neutrophil (I/T) ratios and platelet counts were determined. At study entry, the plasma GCSF and TNF-alpha levels were similar. On day 4, there was no significant change in GCSF levels in either groups, whereas there was a significant decrease in TNF-alpha levels in the treatment group. ANC and INC of the treatment group also increased significantly. The I/T ratio continued at the same level in the treatment group, but decreased significantly on days 4 and 7 day in the control group. The length of time on the neonatal intensive care unit (NICU) was significantly shorter in the treatment group. In conclusion, early administration of 3 daily doses of rGCSF (5 microg/kg per day) to non-neutropenic, preterm infants who had presumed sepsis increased circulating ANC and INC, decreased plasma TNF-alpha levels and shortened the length of time on the NICU.     

Microscopic nephrocalcinosis and hypercalciuria in nephrotic syndrome

Focal calcification is an occasional tubular abnormality seen in minimal-change nephrotic syndrome. Nephrocalcinosis was also reported in premature infants as a consequence of hypercalciuria resulting from long-term furosemide therapy. We describe 4 nephrotic children (3 minimal change, 1 diffuse proliferative glomerulonephritis) with transient hypercalciuria and intraluminal calcifications in renal histopathological specimens without radiologic evidence of renal calcification. These children were resistant to corticosteroid therapy and were receiving furosemide therapy along with albumin for management of oedema. Two of the children also had urinary infection. We were concerned that children with nephrotic syndrome are at risk for nephrocalcinosis, and urinary calcium and pH should be monitored carefully during prolonged furosemide use, especially in children with nephrotic syndrome with reduced initial responsiveness to corticosteroid therapy. HUM PATHOL 31:1363:1367.     

Genotyping of clinical Rhodotorula mucilaginosa isolates by pulsed field gel electrophoresis

Identification and typing of fungal isolates is a prerequisite for control and prevention of nosocomial infections. As the discriminatory power of phenotypic methods is not sufficient for epidemiological purposes, genotyping methods such as DNA fingerprinting, random amplification of polymorphic DNA (RAPD) analysis, or pulsed field gel electrophoresis (PFGE) are preferred. To our knowledge, this study is the first application of PFGE for typing Rhodotorula mucilaginosa strains. The PFGE patterns of six clinical isolates produced two different karyotypes, which were confirmed by RAPD analysis. Five strains isolated from bloodstream infections from three different institutions showed the same karyotype and RAPD patterns, while the urological specimen differed slightly.