Role of the nitric oxide pathway in ischemia-reperfusion injury in isolated perfused guinea pig lungs

We examined the role of the nitric oxide (NO) pathway on ischemia-reperfusion injury via the use of isolated perfused guinea pig lungs. We administered both L-Arginine and N-nitro-L-arginine methyl ester (L-NAME) to the lungs in or after 3 h of ischemia. We observed pulmonary artery pressures as well as tissue and perfusate malondialdehyde (MDA) and glutathione (GSH) levels. We observed that L-NAME significantly increased both tissue and perfusate GSH levels and pulmonary artery pressures, but it decreased both tissue and perfusate MDA levels. On the other hand, L-arginine significantly decreased pulmonary artery pressure and both tissue and perfusate glutathione levels, but it increased both tissue and perfusate MDA levels. Electron microscopic evaluation supported our findings by indicating the preservation of lamellar bodies of type II pneumocytes. We concluded that L-NAME administration during reperfusion improves lung recovery from ischemic injury.     

Insertion/Deletion Polymorphism and Serum Activity of the Angiotensin-Converting Enzyme in Turkish Patients with Obstructive Sleep Apnea Syndrome

This study determined the allelic frequency and genotypic distribution of an angiotensin-converting enzyme (ACE) polymorphism and serum ACE activity in Turkish patients with obstructive sleep apnea syndrome (OSAS). A colorimetric assay measured serum ACE activity in 73 of 97 subjects. Frequencies for II, ID, and DD genotypes were 19.6, 53.6, and 26.8% in the OSAS group and 15, 38, and 47% in the control group, respectively (P = 0.02). The I allele frequency was higher in the OSAS group than in the healthy control group (P = 0.02). Carrying the I allele (II or ID genotypes) increased OSAS risk 2.41 times in the Turkish population. Mean ACE activity was significantly lower in patients with the II genotype than in the DD genotype (P = 0.011), and ACE activity was significantly lower in patients with severe OSAS than in those with mild OSAS (P = 0.006). Our results suggest that II and ID genotypes of the ACE gene increase the risk of developing OSAS in the Turkish population.     

Anterolateral thigh flap in the treatment of postburn flexion contractures of the knee

The use of the anterolateral thigh fasciocutaneous flap in the reconstruction of soft-tissue defects around the knee among burn patients is described. The anterolateral thigh fasciocutaneous flap was used for eight patients (all male; mean age, 45 years; age range, 32 to 60 years). Flexion contracture was observed for seven patients with unhealed wounds and one patient with a healed burn wound. The anterolateral thigh flap was used as a free flap for six patients and as a distally based island flap for two patients. The flaps ranged from 8 to 17 cm in width and from 12 to 30 cm in length. Seven flaps were based on a musculocutaneous perforator, and two of them were thinned before transfer to the defect. A true septocutaneous perforator was observed in only one case. The mean follow-up period was 12.5 months (range, 3 to 23 months). Only one flap exhibited distal superficial necrosis, which did not compromise the final result. All patients returned to ambulatory status in 15 to 22 days. Extensor splints were applied to prevent mobilization of the skin graft at the flap donor site for only 7 days. The anterolateral thigh flap has many advantages for the reconstruction of postburn flexion contracture of the knee, as follows: (1) very large thin flaps can be elevated, (2) the two-team approach is possible, (3) color and texture matches are good, (4) the donor-site scar can be easily hidden, and (5) the technique allows early mobilization and patients can return to normal daily activity in a short time. Free or distally based anterolateral thigh flaps are a good choice, both aesthetically and functionally, for the reconstruction of soft-tissue defects of the knee region.     

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer

This study was designed to investigate, in the Turkish population, an association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer. Our study was carried out in 35 patients with gastric cancer (20 men, 15 women) and 144 controls (75 men, 69 women) and 52 colorectal cancer (31 men, 21 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in cases versus controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 14.3% of gastric cancer versus 10.4% of controls. MTHFR C677T frequencies of the CC, CT and TT genotypes among colorectal cancer patients were 34.6%, 51.9% and 13.5%, respectively. MTHFR C677T polymorphism may not be important in an individual's susceptibility to gastric and colorectal cancer in Turkey and may not be a useful marker for identifying patients at high risk of developing gastric and colorectal cancer.     

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in f?broblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.     

Immune responses in multiple hosts to Nucleocapsid Protein (NP) of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

In 2019, the World Health Organization declared 3 billion to be at risk of developing Crimean Congo Hemorrhagic Fever (CCHF). The causative agent of this deadly infection is CCHFV. The data related to the biology and immunology of CCHFV are rather scarce. Due to its indispensable roles in the viral life cycle, NP becomes a logical target for detailed viral immunology studies. In this study, humoral immunity to NP was investigated in CCHF survivors, as well as in immunized mice and rabbits. Abundant antibody response against NP was demonstrated both during natural infection in humans and following experimental immunizations in mice and rabbits. Also, cellular immune responses to recombinant NP (rNP) was detected in multispecies. This study represents the most comprehensive investigation on NP as an inducer of both humoral and cellular immunity in multiple hosts and proves that rNP is an excellent candidate warranting further immunological studies specifically on vaccine investigations.     

The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study

Background

Burkholderia cepacia complex (BCC) bacteria are highly virulent, typically multidrug-resistant, opportunistic pathogens in cystic fibrosis (CF) patients and other immunocompromised individuals. B. vietnamiensis is more often susceptible to aminoglycosides than other BCC species, and strains acquire aminoglycoside resistance during chronic CF infection and under tobramycin and azithromycin exposure in vitro, apparently from gain of antimicrobial efflux as determined through pump inhibition. The aims of the present study were to determine if oxidative stress could also induce aminoglycoside resistance and provide further observations in support of a role for antimicrobial efflux in aminoglycoside resistance in B. vietnamiensis.

Findings

Here we identified hydrogen peroxide as an additional aminoglycoside resistance inducing agent in B. vietnamiensis. After antibiotic and hydrogen peroxide exposure, isolates accumulated significantly less [³H] gentamicin than the susceptible isolate from which they were derived. Strains that acquired aminoglycoside resistance during infection and after exposure to tobramycin or azithromycin overexpressed a putative resistance-nodulation-division (RND) transporter gene, amrB. Missense mutations in the repressor of amrB, amrR, were identified in isolates that acquired resistance during infection, and not in those generated in vitro.

Conclusions

These data identify oxidative stress as an inducer of aminoglycoside resistance in B. vietnamiensis and further suggest that active efflux via a RND efflux system impairs aminoglycoside accumulation in clinical B. vietnamiensis strains that have acquired aminoglycoside resistance, and in those exposed to tobramycin and azithromycin, but not hydrogen peroxide, in vitro. Furthermore, the repressor AmrR is likely just one regulator of the putative AmrAB-OprM efflux system in B. vietnamiensis.     

<Emphasis Type="Italic">Nonomuraea insulae</Emphasis> sp. nov., isolated from forest soil

Strain H2R21^T, a novel actinobacterium, isolated from a forest soil sample collected from Heybeliada, Istanbul, Turkey, and a polyphasic approach was used for characterisation of the strain. Chemotaxonomic and morphological characterisation of strain H2R21^T indicated that it belongs to the genus Nonomuraea. 16S rRNA gene sequence similarity showed that the strain is closely related to Nonomuraea purpurea 1SM4-01^T (99.1%) and Nonomuraea solani CGMCC 4.7037^T (98.4%). DNA–DNA relatedness values were found to be lower than 70% between the isolate and its phylogenetic neighbours N. purpurea 1SM4-01^T, N. solani CGMCC 4.7037^T and Nonomuraea rhizophila YIM 67092^T. The whole cell hydrolysates of strain H2R21^T were found to contain meso-diaminopimelic acid as the diagnostic diamino acid and glucose, madurose, mannose and ribose as the cell sugars. The polar lipids were identified as phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, dihydroxy-phosphatidylethanolamine, phosphatidylinositol, glycophosphatidylinositol, two glycophospholipids and two unidentified lipids. The predominant menaquinones were identified as MK-9(H₄) and MK-9(H₆). The major fatty acids were found to be iso-C_16:0, iso-C_16:0 2OH and C_17:0 10-methyl. On the basis of DNA–DNA relatedness data and some phenotypic characteristics, it is evident that strain H2R21^T can be distinguished from the closely related species in the genus Nonomuraea. Thus, it is concluded that strain H2R21^T represents a novel species of the genus Nonomuraea, for which the name Nonomuraea insulae sp. nov. is proposed. The type strain is H2R21^T (= DSM 102915^T = CGMCC 4.7338^T = KCTC 39769^T).