Synergistic antinociceptive interaction between acetaminophen or metamizol and B vitamins in the formalin test

There is evidence that B vitamins produce antinociception in animals. However, potentiation of NSAID‐induced antinociception by B vitamins is unclear. The current study was designed to investigate the antinociceptive interaction between a mixture of B vitamins and either acetaminophen or metamizol. Acetaminophen (56–316 mg/kg), metamizol (32–178 mg/kg), and the mixture of B vitamins (32–178 mg/kg of thiamine, pyridoxine, and cyanocobalamin in a 100:100:1 proportion, respectively) or a combination of each drug with the B vitamins mixture was administered orally to female Wistar rats, and the antinociceptive effect determined in the formalin test. Isobolographic analyses were used to define the nature of the interaction between NSAIDs and B vitamins. Oral administration of either drug produced a dose‐related antinociceptive effect. Isobolographic analyses revealed that both acetaminophen or metamizol and the B vitamins mixture interacted synergistically in the formalin test, suggesting that these two combinations could be useful in treating inflammatory pain states. Drug Dev. Res. 66:286–294, 2006. © 2006 Wiley‐Liss, Inc.     

Evaluation of the toxicology,anti-lipase,and antioxidant effects of Callistemon citrinus in rats fed with a high fat-fructose diet

ContextCallistemon citrinus Skeels (Myrtaceae) exhibits many biological activities.ObjectiveThis study analyzes for the first time, the toxicity, obesogenic, and antioxidant effects of C. citrinus in rats fed with a high fat-fructose diet (HFFD).Materials and methodsFour studies using male Wistar rats were conducted: (a) 7 groups (n = 3): control (corn oil) and ethanol extract of C. citrinus leaf (single oral dose at 100–4000 mg/kg) for acute toxicity; (b) 2 groups (n = 8): control (corn oil) and C. citrinus (1000 mg/kg/day) for 28 days for subacute toxicity; (c) 3 groups (n = 4) with single oral dose of lipid emulsion: control (lipid emulsion), C. citrinus and orlistat (250 and 50 mg/kg, respectively) for lipid absorption; (d) 4 groups (n = 6): control (normal diet) and 3 groups fed with HFFD: HFFD only, C. citrinus and simvastatin (oral dose 250 and 3 mg/kg, respectively) for 13 weeks. Antioxidant enzymes and biomarkers were evaluated and inhibition of pancreatic lipase was determined in vitro.ResultsToxicological studies of C. citrinus showed no differences in biochemical parameters and lethal dose (LD₅₀) was higher than 4000 mg/kg. C. citrinus inhibited pancreatic lipase activity, with IC₅₀ of 392.00 µg/mL, and decreased lipid absorption by 70%. Additionally, it reduced the body weight 22%, restored the activities of antioxidant enzymes, and reduced the biomarkers of oxidative stress.ConclusionsCallistemon citrinus showed an effect against oxidative stress by reducing biomarkers and induced antioxidant system, without toxic effects.     

Global Extension and Predominance of Human Metapneumovirus A2 Genotype with Partial G Gene Duplication

Human metapneumovirus (HMPV) is an important respiratory pathogen and is divided in two main groups (A and B). HMPV strains with partial duplications (111-nt and 180-nt duplication) of the G gene have been reported in recent years. Since the initial reports, viruses with these characteristics have been reported in several countries. We analyzed all complete HMPV G gene ectodomain sequences available at GenBank to determine if viruses with 111-nt or 180-nt duplication have become the leading HMPV strains worldwide, and to describe their temporal and geographic distribution. We identified 1462 sequences that fulfilled study criteria (764 HMPV A and 698 HMPV B) reported from 37 countries. The most frequent HMPV A genotype was A2b2 (n = 366), and the most frequent B genotype was B2 (n = 374). A total of 84 sequences contained the 111-nt duplication, and 90 sequences contained the 180-nt duplication. Since 2016, viruses with a partial duplication comprise the most frequent HMPV A sequences globally and have displaced other HMPV A viruses in Asia, Europe, and South America; no sequences of viruses with partial duplication have been reported in North America or Africa so far. Continued surveillance of HMPV is required to identify the emergence and spread of epidemiologically relevant variants.     

Impaired Vagal Activity in Long-COVID-19 Patients

Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.     

EXPERIMENTS ON THE CONVERSION OF TYPHUS STRAINS

Two types of strains of typhus virus are observed in Mexico: first the murine type which is obtained from wild rats in nature, from isolated endemic cases, and from cases during short epidemic outbreaks, and second, the epidemic type of strains which is obtained from long standing serious epidemics. Some of these epidemic strains correspond entirely to strains of historic Old World typhus. Other strains which in their experimental behavior are intermediate between these two types of strains were isolated from the same epidemic. A method is described by which these epidemic non-orchitic strains can be converted into murine strains regularly causing scrotal lesion in guinea pigs and a highly fatal disease in rats. The same results were obtained with an Old World strain of epidemic typhus. The method, which consists of daily blood injections into intraperitoneally inoculated rats, is based on the observation that Rickettsia prowazeki multiplies only within cells which come in constant or frequent contact with fresh blood. It is concluded from our experiments that there does not exist any real difference between the virus of historic Old World typhus and the murine New World typhus. Both are considered to be of murine origin. The murine strains represent the original form of the virus of typhus, whereas the epidemic strains are the result of a prolonged propagation in the cycle man-louse-man.     

Oxidative dehalogenation of trichlorophenol catalyzed by a promiscuous artificial heme-enzyme

The miniaturized metalloenzyme Fe(iii)-mimochrome VI*a (Fe(iii)-MC6*a) acts as an excellent biocatalyst in the H₂O₂-mediated oxidative dehalogenation of the well-known pesticide and biocide 2,4,6-trichlorophenol (TCP). The artificial enzyme can oxidize TCP with a catalytic efficiency (k_cat/K^TCP_m = 150 000 mM⁻¹ s⁻¹) up to 1500-fold higher than the most active natural metalloenzyme horseradish peroxidase (HRP). UV-visible and EPR spectroscopies were used to provide indications of the catalytic mechanism. One equivalent of H₂O₂ fully converts Fe(iii)-MC6*a into the oxoferryl-porphyrin radical cation intermediate [(Fe(iv) O)por˙⁺], similarly to peroxidase compound I (Cpd I). Addition of TCP to Cpd I rapidly leads to the formation of the corresponding quinone, while Cpd I decays back to the ferric resting state in the absence of substrate. EPR data suggest a catalytic mechanism involving two consecutive one-electron reactions. All results highlight the value of the miniaturization strategy for the development of chemically stable, highly efficient artificial metalloenzymes as powerful catalysts for the oxidative degradation of toxic pollutants.

The artificial metalloenzyme FeMC6*a is able to perform the H₂O₂-mediated dechlorination of 2,4,6-trichlorophenol with unrivalled catalytic efficiency, highlighting its potential application for the removal of toxic pollutants.     

Magnesium-to-Calcium Ratio and Mortality from COVID-19

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (_95%CI 1.6–29.1) in the whole population, 4.93 (_95%CI 1.4–19.1, p = 0.003) in men, and 3.93 (_95%CI 1.6–9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.     

Antioxidant Effects of Selenium in Rat Brain and the Stimulating Role of Nitric Oxide

Abstract

Objective: To evaluate the antioxidant effect of selenium on Na<PRE>+</PRE>, K<PRE>+</PRE>-ATPase in rat brain in the presence of nitric oxide.

Methods: Male Wistar rats (70 g) were treated as follows: group 1 received 1 μg of i.p. sodium nitroprusside per kg (SNP), group 2 received 5 μg sodium selenite during 20 days, group 3 received sodium selenite 5 μg+SNP 1 μg and the control group received vehicle 50 μl (0.9% NaCl), same period and route. At the end of treatment, animals were sacrificed and their brain dissected into cortex, hemispheres, cerebellum and brain stem in order to determine lipid peroxidation (TBARS), Na<PRE>+</PRE>, K<PRE>+</PRE> ATPase and total ATPase in each section. Blood hemoglobin concentration (Hb) and prostate weight were also assessed.

Results: A significant increase of Hb in blood and of proteins in cortex and hemisphere was detected, but TBARS values fell due to the effect of sodium selenite in all examined regions, except for cerebellum. ATPase activity declined in all groups and regions with and without NTP. We conclude that diet supplementary selenium to inhibit NO generation can be a useful treatment in chronic inflammatory diseases.