Ageing‐associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca2+ homeostasis and promotes cardiac dysfunction

The prevalence of death from cardiovascular disease is significantly higher in elderly populations; the underlying factors that contribute to the age‐associated decline in cardiac performance are poorly understood. Herein, we identify the involvement of sodium/glucose co‐transporter gene (SGLT2) in disrupted cellular Ca²⁺‐homeostasis, and mitochondrial dysfunction in age‐associated cardiac dysfunction. In contrast to younger rats (6‐month of age), older rats (24‐month of age) exhibited severe cardiac ultrastructural defects, including deformed, fragmented mitochondria with high electron densities. Cardiomyocytes isolated from aged rats demonstrated increased reactive oxygen species (ROS), loss of mitochondrial membrane potential and altered mitochondrial dynamics, compared with younger controls. Moreover, mitochondrial defects were accompanied by mitochondrial and cytosolic Ca²⁺ ([Ca²⁺]_i) overload, indicative of disrupted cellular Ca²⁺‐homeostasis. Interestingly, increased [Ca²⁺]_i coincided with decreased phosphorylation of phospholamban (PLB) and contractility. Aged‐cardiomyocytes also displayed high Na⁺/Ca²⁺‐exchanger (NCX) activity and blood glucose levels compared with young‐controls. Interestingly, the protein level of SGLT2 was dramatically increased in the aged cardiomyocytes. Moreover, SGLT2 inhibition was sufficient to restore age‐associated defects in [Ca²⁺]_i‐homeostasis, PLB phosphorylation, NCX activity and mitochondrial Ca²⁺‐loading. Hence, the present data suggest that deregulated SGLT2 during ageing disrupts mitochondrial function and cardiac contractility through a mechanism that impinges upon [Ca²⁺]_i‐homeostasis. Our studies support the notion that interventions that modulate SGLT2‐activity can provide benefits in maintaining [Ca²⁺]_i and cardiac function with advanced age.     

A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.     

A new Chondrostoma species from the Büyük Menderes River Basin,Turkey (Teleostei: Cyprinidae)

In a study of the fishes of the Büyük Menderes River Basin, Aegean region of Turkey, two populations of Chondrostoma were found which showed clearly distinctive characters: the population from the Upper B. Menderes (I??kl? Lake) was attributed to C. meandrense Elvira, 1987, while the population from the Çine Stream in the Lower B. Menderes River basin proved to be a hitherto undescribed species: Chondrostoma turnai sp. n. Altogether 24 metric and 7 meristic parameters were compared. The new species is distinguished from C. meandrense and all other cogeners by a combination of the number of lateral line scales, the number of scale rows between the lateral line and the dorsal-fin origin, the number of scale rows of the lateral line and pelvic-fin origin, and the number of gill rakers on the first gill arch.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:811C213D-BEDD-4C8C-AE57-BFFA7964781A     

Characteristics of Capoeta oguzelii,a new species of cyprinid fish from the Ezine Stream,Black Sea basin,Turkey (Teleostei: Cyprinidae)

Four species of Capoeta (C. baliki, C. banarescui, C. sieboldii and C. ekmekciae) have been reported from Black Sea drainages, to date. We recognised an additional species in the Ezine Stream in the Southern Black Sea basin. Based on the analysis of 21 metric and 8 meristic data, we concluded that the Ezine Stream population forms a distinct, unnamed species, which we have described as Capoeta oguzelii sp. n. This species can be distinguished from all other Capoeta species by the following combination of characteristics: small size, presence of only one pair of barbels, absence of a keratinised edge of the lower jaw, a weakly ossified last simple dorsal fin ray, 7–10 gill rakers on the first gill arch and 7½ branched dorsal fin rays.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:066CC44A-3806-4DB7-8E88-AD971200E1EE     

Continuous production of 1,3-propanediol using raw glycerol with immobilized Clostridium beijerinckii NRRL B-593 in comparison to suspended culture

The continuous production of 1,3-propanediol (1,3-PDO) was investigated with Clostridium beijerinckii NRRL B-593 using raw glycerol without purification obtained from a biodiesel production process. Ceramic rings and pumice stones were used for cell immobilization in a packed-bed bioreactor. For comparison purpose, a control bioreactor with suspended culture was also run. The effect of hydraulic retention time (HRT) on the production of 1,3-PDO in both immobilized and suspended bioreactors were also investigated. The study revealed that HRT is an important factor for both immobilized and suspended systems and a HRT of 2 h is the best one in terms of volumetric production rate (g 1,3-PDO/L/h). Furthermore, cell immobilization had also obvious benefits especially for the robustness and the reliability of the production. The results indicated that cell immobilization achieved a 2.5-fold higher productivity in comparison to suspended cell system. Based on our results, continuous production of 1,3-PDO with immobilized cells is an efficient method, and raw glycerol can be utilized without any pretreatment.     

Investigation of the mechanism of nicotine-induced relaxation on the sheep sphincter of Oddi

Possible mechanisms for nicotine-induced relaxation were investigated in the isolated sheep's sphincter of Oddi. Sheep's sphincter of Oddi rings were mounted in tissue bath with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of precontraction induced by carbachol. Nicotine (1 x 10(-5) to 3 x 10(-3) mol/L) produced concentration-dependent relaxation on sphincter of Oddi precontracted by carbachol (10(-6) mol/L). Nicotine-induced relaxation was 72.8 +/- 4.2% of precontraction with carbachol (10(-6) mol/L) (mean pD2 value, 3.76 +/- 0.05 mol/L). Nicotine-induced relaxation was not affected by N(w)-nitro L-arginine methyl ester (L-NAME) (3 x 10(-5) mol/L), methylene blue (10(-5) mol/L), indomethacin (10(-5) mol/L), hexamethonium (10(-5) mol/L), glibenclamide (10(-5) mol/L), 4-aminopyridine (10(-3) mol/L), tetraethylammonium (3 x 10(-4) mol/L), clotrimazole (10(-6) mol/L), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) (10(-6) mol/L), and anthracene-9-carboxylate (9-AC) (10(-6) mol/L), but potentiated by bupivacain (10(-5) mol/L). A calcium-antagonizing effect of nicotine was not observed. The results suggest that nicotine-induced relaxation of the sheep's sphincter of Oddi is not mediated by the release of prostaglandins, nitric oxide (NO), or a related substance; by the activation of potassium channels or chloride channels; or by the stimulation of nicotinic cholinoceptors. Potentiation of the nicotine-induced relaxation by bupivacain indicates that blockade of sodium channels may play a role in this relaxation.     

The effect of melatonin against oxidative damage during total-body irradiation in rats

Melatonin has been reported to participate in the regulation of a number of important physiological and pathological processes. Melatonin, which is a powerful endogenous antioxidant, may play a role in the prevention of oxidative damage. The aim of this study was to investigate the effect of pretreatment with melatonin (5 mg kg(-1) and 10 mg kg(-1)) on gamma-radiation-induced oxidative damage in plasma and erythrocytes after total-body irradiation with a single dose of 5 Gy. Total-body irradiation resulted in a significant increase in plasma and erythrocyte MDA levels. Melatonin alone increased the levels of SOD and GSH-Px. Erythrocyte and plasma MDA levels in irradiated rats that were pretreated with melatonin (5 or 10 mg kg(-1)) were significantly lower than those in rats that were not pretreated. There was no significant difference between the effects of 5 and 10 mg kg(-1) on plasma MDA activities and CAT activities. However, erythrocyte MDA levels showed a dose-dependent decrease, while GSH-Px activities increased with dose. Our study suggests that melatonin administered prior to irradiation may protect against the damage produced by radiation by the up-regulation of antioxidant enzymes and by scavenging free radicals generated by ionizing radiation.     

Sexual dimorphism in the otolith shape of shi drum,Umbrina cirrosa (L.), in the eastern Mediterranean Sea: Fish size–otolith size relationships

Little is known about possible differences in sagitta otolith size and shape between sexes of the shi drum, Umbrina cirrosa, and relationships between their body and otolith size. Thus, this study aimed to fill this knowledge gap via examination of 414 sagittal otoliths from 108 male (total length 13.8–26.8 cm) and 99 female (13.5–26.7 cm) U. cirrosa caught between May 2017 and April 2018 in gillnets set at a depth of ~15 m in Mersin Bay, Eastern Mediterranean Sea. No statistical differences were observed between the shape indices of the left-sided and right-sided sagitta. However, there were significant differences in the size and shape of otoliths between males and females. The slopes of allometric power functions from otolith width × fish sizes gave significant differences between males and females (ANCOVA, P < 0.05). The relationship for length × weight of otoliths from both males and females showed isometric growth, whereas the relationship of otolith width × otolith weight showed positive allometry. Negative allometric growth was observed for the relationship otolith length × otolith width. In summary, this study revealed the presence of sexual dimorphism in the otolith shape of U. cirrosa, and the data on regression relationships of fish-otolith sizes can be used to estimate fish size from U. cirrosa otolith sizes.     

Gender-based acute outcome in percutaneous coronary intervention of chronic total coronary occlusion

Background

Percutaneous coronary intervention (PCI) of total chronic coronary occlusion (CTO) still remains a major challenge. Insignificant data are reported in the literature about gender differences in CTO-PCI in the era of new drug-eluting stents. In this study we analysed the impact of gender on procedural characteristics, complications and acute results.

Methods

Between 2010–2015 we included 780 consecutive patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied.

Results

Patients undergoing CTO-PCI were mainly men (84%). Male patients were younger (66.9 years ±10.6 vs. 61.1 years ±10.4; p < 0.001), more often smokers, but less frequently had a history of coronary artery disease (24.4% vs. 32.7%; p = 0.085) compared with female patients. Female patients more often had diabetes mellitus (29.6% vs. 26.7%; p = 0.55) and hypertension (82.7% vs. 80.7%; p = 0.55). There were no differences with respect to the amount of contrast fluid, fluoroscopy time and examination time as well as to the length of the stent or the number of the stents. The stent diameter was slightly smaller in women, which was not surprising because the lumen calibre tends to be smaller in women than in men (3.0?mm (2.5–3) vs. 3.0?mm (3–3.5); p < 0.001). The success rates were 81.0% in women and 80.1% in men. There was no significant interaction between gender and procedural success and complication rates.

Conclusions

Our retrospective study suggests that women and men have a comparable success rate at a low complication rate after recanalisation of CTO.