The genotoxic and cytotoxic effects of nicotine in the mouse bone marrow

The objective of the present study was to investigate the potential of nicotine to induce micronucleated polychromatic erythrocytes (MNPCE) in bone marrow of male and female mice. Cyclophosphamide at 40mg/kg was used as positive control clastogen. Single doses of 4, 8 or 16mg/kg nicotine were given via oral intubation and bone marrow was sampled at 18, 24, 30, 36 and 48h after treatment. Cyclophosphamide yielded the expected positive results. Despite the evident signs of acute toxicity shown by the animals, mainly at the 8 and 16mg/kg doses of nicotine, and the reduction in the % PCE, the results show that the MNPCE frequency in male and female mice was not affected by treatment with any of the selected doses of nicotine, in either of the sampling times 18 or 24h. However, at 30 and 36h after treatment, the MNPCE showed significant increases in both genders after doses of 8 and 16mg/kg. A sex-dependent response was recorded, with males having more MNPCE than females after treatment with 8 or 16mg/kg nicotine and sampling at 30h. However, at 36h more MNPCE were induced in females than in males, suggesting different degrees of dose interaction in the sexes under the conditions of the assay. The response was directly correlated with bone-marrow toxicity, as greater bone-marrow suppression was noted in females than in males when 36h samples were examined. By 48h recovery was observed even though the cytotoxicity was high. These findings suggest that nicotine at high doses and after prolonged time intervals is genotoxic and cytotoxic for mouse bone marrow.     

Rheumatoid peripheral blood phagocytes are primed for activation but have impaired Fc-mediated generation of reactive oxygen species

Significant levels of circulating immune complexes (ICs) containing rheumatoid factors and immunoglobulin G in peripheral blood are a characteristic feature of rheumatoid arthritis (RA). ICs interact through Fcγ receptors (FcγR) to activate phagocytes in numerous inflammatory processes. The high concentration of neutrophils in synovial fluid during active phases of the disease, together with their destructive capacity, pose important questions as to their role in the pathogenesis of RA. Functional defects in RA or control peripheral blood neutrophil FcγRs were examined with a specific FcγR-mediated reactive oxygen species (ROS) assay. Heterologous cross-linking of FcγRIIa and FcγRIIIb on neutrophils resulted in a significantly decreased production of ROS by RA cells compared with controls matched for age and sex. However, expression and homologous ligation of receptors did not differ between these groups. These data suggest that neutrophil priming does occur before emigration into the joint and that blood neutrophils from patients with RA have a functional impairment in cooperative FcγR-mediated ROS generation. This may account for the increased susceptibility to bacterial infection that arises in patients with severe disease.     

Influence of a niosomal formulation on the oral bioavailability of acyclovir in rabbits

The purpose of this research was to prepare acyclovir niosomes in a trial to improve its poor and variable oral bioavailability. The nonionic surfactant vesicles were prepared by the conventional thin film hydration method. The lipid mixture consisted of cholesterol, span 60, and dicetyl phosphate in the molar ratio of 65:60:5, respectively. The percentage entrapment was approximately 11% of acyclovir used in the hydration process. The vesicles have an average size of 0.95 microm, a most probable size of 0.8 microm, and a size range of 0.4 to 2.2 microm. Most of the niosomes have unilamellar spherical shape. In vitro drug release profile was found to follow Higuchi's equation for free and niosomal drug. The niosomal formulation exhibited significantly retarded release compared with free drug. The in vivo study revealed that the niosomal dispersion significantly improved the oral bioavailability of acyclovir in rabbits after a single oral dose of 40 mg kg(-1). The average relative bioavailability of the drug from the niosomal dispersion in relation to the free solution was 2.55 indicating more than 2-fold increase in drug bioavailability. The niosomal dispersion showed significant increase in the mean residence time (MRT) of acyclovir reflecting sustained release characteristics. In conclusion, the niosomal formulation could be a promising delivery system for acyclovir with improved oral bioavailability and prolonged drug release profiles.     

降解烤烟秸秆和烟碱菌株的筛选及其产酶特性

摘要:【目的】为获得能够降解烤烟秸秆和烟碱的菌株,并探索其降解烤烟秸秆的利用途径。【方法】以烤烟秸秆为唯一碳氮源,从烟田土壤中进行了菌株的筛选。采用形态学观察、生理生化特性鉴定、16S rRNA基因序列鉴定等方法对该菌株进行了鉴定,并对其以烤烟秸秆为底物进行液态发酵的产酶活性和木质纤维素降解效果进行了测定。【结果】结果表明:该菌株为巨大芽孢杆菌(Bacillus megaterium)。在以烤烟秸秆为主要营养物质液态发酵条件下该菌株具有较强的木质素降解能力,最大漆酶活力达到418.52 U/L,而木质素过氧化物酶和锰过氧化物酶的最大酶活分别为19.71 U/L 和64.71 U/L。此外,发酵20 d后该菌能够完全降解发酵液中的烟碱。【结论】本研究筛选到了1株能够较好降解烤烟秸秆和完全降解烟碱的巨大芽孢杆菌(Bacillus megaterium),且该菌株具有利用烤烟秸秆生产漆酶的应用价值。     

Migratory birds as the vehicle of transmission of multi drug resistant extended spectrum β lactamase producing Escherichia fergusonii,an emerging zoonotic pathogen

The acquisition of multi-drug resistance (MDR) genes by pathogenic bacterial bugs and their dispersal to different food webs has become a silent pandemic. The multiplied use of different antibacterial therapeutics during COVID-19 pandemic has accelerated the process among emerging pathogens. Wild migratory birds play an important role in the spread of MDR pathogens and MDR gene flow due to the consumption of contaminated food and water. Escherichia fergusonii is an emerging pathogen of family Enterobacteriaceae and commonly causes disease in human and animals. The present study focused on the isolation of E. fergusonii from blood, saliva, and intestine of selected migratory birds of the Hazara Division. The sensitivity of isolated strains was assessed against ten different antibiotics. The isolation frequency of E. fergusonii was 69%. In blood samples, a high rate of resistance was observed against ceftriaxone (80%) followed by ampicillin (76%) whereas, in oral and intestinal samples, ceftriaxone resistant strains were 56% and 57% while ampicillin resistance was 49% and 52% respectively. The overall ceftriaxone and ampicillin-resistant cases in all three sample sources were 71% and 65% respectively. In comparison to oral and intestinal samples, high numbers of ceftriaxone-resistant strains were isolated from the blood of mallard while ampicillin-resistant strains were observed in blood samples of cattle egrets. 16S rRNA-based confirmed strains of E. fergusonii were processed for detection of CTX-M and TEM-1 gene through Polymerase chain reaction (PCR) after DNA extraction. Hundred percent ceftriaxone resistant isolates possessed CTX-M and all ampicillin-resistant strains harbored TEM-1 genes. Amplified products were sequenced by using the Sanger sequencing method and the resulted sequences were checked for similarity in the nucleotide Database through the BLAST program. TEM-1 gene showed 99% and the CTX-M gene showed 98% similar sequences in the Database. The 16S rRNA sequence and nucleotide sequences for TEM-1 and CTX-M genes were submitted to Gene Bank with accession numbers {"type":"entrez-nucleotide","attrs":{"text":"LC521304","term_id":"1806500528","term_text":"LC521304"}}LC521304, {"type":"entrez-nucleotide","attrs":{"text":"LC521306","term_id":"1806500530","term_text":"LC521306"}}LC521306, {"type":"entrez-nucleotide","attrs":{"text":"LC521307","term_id":"1806500532","term_text":"LC521307"}}LC521307 respectively. We posit to combat MDR gene flow among the bacterial pathogens across different geographical locations, regular surveillance of new zoonotic pathogens must be conducted.     

Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

Alpha-lipoic acid (ALA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of ALA has recently been reported. This study was designed to investigate whether ALA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin (STZ; 55 mg/kg (intraperitoneal). Diabetic and normal rats were treated with ALA (100 mg kg^?1 day^?1) for 45 days. ALA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in ALA-treated normal rats (P?<?0.01) together with a significant elevation (P?<?0.001) in the plasma levels of advanced oxidation protein products in ALA-treated normal rats and in ALA?+?STZ-diabetic rats compared with the normal control rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has emerged as the major source of superoxide anion and enhanced oxidative damage in heart failure. ALA supplementation increased the myocardial immunoreactivity of p47phox subunit of NADPH oxidase in both normal nondiabetic and diabetic rats reflecting its pro-oxidant effect. Data showed that ALA supplementation failed to prevent cardiac complications in diabetic rats and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. The pro-oxidant effects of ALA suggest that careful selection of appropriate doses of ALA in reactive oxygen species-related diseases are critical.     

"Wet dog shakes" during olfactory bulb kindling

Kindling phenomenon provides an experimental model of limbic secondarily generalized epilepsy. It can be easily obtained by stimulation of the olfactory bulb (OB) which is strongly connected to limbic structures. The after-discharge induced by subconvulsant electrical stimulations, is followed by a behavioral phenomenon, named Wet Dog Shakes (WDS). In the course of the Rat OB kindling, the development of WDS is biphasic: 1) an ascendant phase during the first three stages, and 2) a descendant phase in the stages 4 and 5, that may give evidence of the installation and the intensification of the kindling process. The significance of this behavior in seizure generalization is discussed.