Deletion of murine astrocytic vesicular nucleotide transporter increases anxiety and depressive-like behavior and attenuates motivation for reward.

Astrocytes are multi-functional glial cells in the central nervous system that play critical roles in modulation of metabolism, extracellular ion and neurotransmitter levels, and synaptic plasticity. Astrocyte-derived signaling molecules mediate many of these modulatory functions of astrocytes, including vesicular release of ATP. In the present study, we used a unique genetic mouse model to investigate the functional significance of astrocytic exocytosis of ATP. Using primary cultured astrocytes, we show that loss of vesicular nucleotide transporter (Vnut), a primary transporter responsible for loading cytosolic ATP into the secretory vesicles, dramatically reduces ATP loading into secretory lysosomes and ATP release, without any change in the molecular machinery of exocytosis or total intracellular ATP content. Deletion of astrocytic Vnut in adult mice leads to increased anxiety, depressive-like behaviors, and decreased motivation for reward, especially in females, without significant impact on food intake, systemic glucose metabolism, cognition, or sociability. These behavioral alterations are associated with significant decreases in the basal extracellular dopamine levels in the nucleus accumbens. Likewise, ex vivo brain slices from these mice show a strong trend toward a reduction in evoked dopamine release in the nucleus accumbens. Mechanistically, the reduced dopamine signaling we observed is likely due to an increased expression of monoamine oxidases. Together, these data demonstrate a key modulatory role of astrocytic exocytosis of ATP in anxiety, depressive-like behavior, and motivation for reward, by regulating the mesolimbic dopamine circuitry.

[Retained lens fragments after cataract surgery: Comparison of same-day versus delayed vitrectomy]. / Vitrectomie pour luxation postérieure de fragments cristalliniens après chirurgie de la cataracte : étude comparative.

PURPOSE: To evaluate and to compare functional outcomes and complication rates of the same-day versus delayed pars plana vitrectomy (PPV) for intravitreal retained lens fragments after cataract surgery. METHODS: Retrospective comparative series of 135 eyes with retained lens fragments that underwent PPV between August 2014 and July 2016. Sixty-two eyes received same-day PPV (group 1) and seventy-three eyes underwent delayed PPV (group 2). Outcome measures included best-corrected visual acuity (BCVA) at 6 months and postoperative complications. RESULTS: The mean time to PPV in group 2 was 4.3±5.3 days. Mean axial length, lens fragment size and surgical technique were comparable in both groups. At 6 months, BCVA was 0.27±0.40 logMAR in group 1, and 0.35±0.30 logMAR in group 2, with no significant difference (P=0.205). Fifty-one (82.2%) eyes in group 1 and 53 (72.6%) eyes in group 2 achieved BCVA of+0.30 logMAR (20/40) or better (P=0.183). The most common complications were macular edema, elevated intraocular pressure>25mmHg, and retinal detachment occurring respectively in 10 (16.1%) eyes, 4 (6.4%) eyes and one eye (1.6%) in group 1 and 11 (15.0%) eyes, 5 (6.8%) eyes and 2 (2.7%) eyes in group 2. Overall, the complication rate was similar in both groups (P=1). CONCLUSION: Our study shows that visual acuity outcomes and complication rates were similar regardless of timing of the PPV. The optimal timing of surgery remains a multifactorial decision involving patient preferences, transportation, surgeon availability and severity of the initial presentation.

The interplay between vitamin D and COVID-19: protective or bystander?

The world is currently facing the COVID-19 pandemic, caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to a lack of specific treatment and prophylaxis, protective health measures that can reduce infection severity and COVID-19 mortality are urgently required. Clinical and epidemiological studies have shown that vitamin D deficiency can be linked to an increased risk of viral infection, including COVID-19. Therefore, in this review, we looked at various possible roles of vitamin D in reducing the risk of COVID-19 infection and severity. We describe in this article that individuals at high risk of vitamin D deficiency should consider taking vitamin D supplements to keep optimal concentrations. Moreover, we discuss different possible mechanisms by which vitamin D can efficiently reduce the risk of infections through modulation of innate and adaptive immunity against various types of infections. It is advisable to perform further studies addressing the observed influence of vitamin D levels to reduce the risk of COVID-19 infection and mortality.

Apoptosis during the development of the hepatic steatosis in force-fed ducks and cooking yield implications.

Mule ducks were force-fed for 12 d to determine whether or not signs of apoptosis could occur during the development of the hepatic steatosis induced by the huge quantities of corn ingested twice daily by the birds. Presence of apoptosis in hepatocytes was assessed through the measurements of increased activities of capsase-3 +-7, -8, and -9. From d 0 of the force-feeding period until d 8, activities of the different caspases remained at a low level. On the contrary, at d 10 and d 12, activities of all measured caspases dramatically increased, indicating that apoptosis occurred at this stage, which corresponds to the time of accumulation of large quantities of lipids in the hepatic cells.The melting level of the liver issued from force-feeding ("foie gras") during cooking is a point of interest for processors because it could degrade the quality of this delicate dish. In this study, we used the levels of caspases activities to improve the predictability of foie gras cooking, in addition to other parameters usually used, such as its weight or lipid content. From this improvement, we suggest that part of the variability of melting during cooking of fatty livers could reside in more or less intense activity of hepatic proteases.

[Healthy persons versus patients with diabetes mellitus type 2--choosen parameters in serum and subcutaneous abdominal adipose tissue]. / Zdravé osoby versus pacienti s diagnózou diabetes mellitus 2. typu--vybrané parametry v séru a v subkutánní abdominální tukové tkáni.

UNLABELLED: Endocrinal products of adipocytes (PPARgamma, A-FABP, E-FABP, leptin, adiponectin and others) modulate insulin tissue sensitivity enabling them to participate in the ethiopathogenesis of diabetes mellitus type 2 (DM2T). Persons with DM2T are characterised by typical changes in lipid spectrum (lower HDL-cholesterol and higherTAG) and in the endocrinal function of subcutaneous adipose tissue; adipocytes produce more PPARgamma, A-FABP and E-FABP and less adiponectin. AIMS OF THE STUDY: To measure chosen markers of metabolic syndrome (MS) in serum and in abdominal subcutaneous adipose tissue in healthy persons and patients with DMT2, to determine basic statistical characteristics of investigated parameters and to discus their role in the genesis and progress of the MS. METHODS: Samples of blood and abdominal subcutaneous adipose tissue were collected from each participant (healthy: 7 men and 8 women; diabetics: 18 men, 11 women) to investigate the levels of HDL, TAG, insulin, C-peptide, glycaemia and the concentrations of A-FABP, E-FABP, leptin, adiponectin, resistin, PPARgamma and TNFalpha. RESULTS: In most cases the average concentration of investigated parameters in serum was higher in persons with DM 2 regardless of gender. Lower values were only found for HDL and adiponectin. The same situation prevailed in the subcutaneous adipose tissue. Values of most other parameters (A-FABP, E-FABP, and PPARgamma) were also higher in patients. The values of measured parameters not only differed in healthy and in sick persons but depended on gender. The increase/decrease in concrete parameters was greater in diabetic women than diabetic men. CONCLUSION: Higher concentrations of A-FABP, E-FABP in serum and in subcutaneous adipose tissue in diabetic persons also higher concentrations of PPARgamma in subcutaneous adipose tissue suggest that these investigated parameters are closely associated with obesity and MS. We can assume that in the near future these parameters will be used in clinical work for diagnosis of this syndrome.

Treatment with atorvastatin reduces serum adipocyte-fatty acid binding protein value in patients with hyperlipidaemia.

BACKGROUND: Adipocyte-fatty acid binding protein (A-FABP) is a circulating protein expressed in adipocytes and macrophages. Several recent studies demonstrated that A-FABP might be involved in the pathogenesis of metabolic syndrome, particularly in dyslipidaemia, insulin resistance and atherosclerosis. The aim of this study was to investigate the influence of atorvastatin treatment (20 mg day(-1) for 3 months) on serum A-FABP value in subjects with hyperlipidaemia. MATERIALS AND METHODS: Anthropometric and serum analyses were performed for body mass index, A-FABP, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitive C-reactive protein (hs-CRP), creatine kinase (CK) and glucose on 26 subjects (BMI 30.3 +/- 6.0, mean age 62 +/- 10 years) with hyperlipidaemia who met the criteria: total cholesterol > 5.2 mmol L(-1), LDL cholesterol > 3.3 mmol L(-1) and triglycerides < 3 mmol L(-1). RESULTS: After the 3-month therapy, a significant reduction in total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), glucose (P < 0.001), A-FABP (from 44.6 +/- 26.2 to 38.6 +/- 19.3 g L(-1), P < 0.01), uric acid (P < 0.05), AST (P < 0.05) and triglycerides (P < 0.05) values was observed. No difference was found in BMI, CK, ALT, hs-CRP, or HDL cholesterol values. A significant difference in the serum A-FABP value before and after the therapy remains after the correction for total cholesterol value (P < 0.001). A positive correlation between serum A-FABP and glucose was found (P < 0.05). CONCLUSIONS: In conclusion, our study confirmed in vivo that atorvastatin reduces serum A-FABP by a pleiotropic mechanism and supports the hypothesis that A-FABP is involved in atherosclerotic actions.