Transforming growth factor as a marker beta of nephrogenetic disturbance in congenital obstructive uropathies

The paper presents the results of morphological and immunohistochemical studies of the kidneys and ureters obtained at surgery in 25 children aged from 2 days to 3 years who had congenital obstructive uropathies. The morphological study revealed varying renal tissue dysplasia concurrent with dysplasia of the prepelvic or distal ureter. Immunohistochemically, the kidneys showed a pronounced expression of TGFbeta1, TGF(1R1 and R2 in the nephrocytes of non-differentiated and collecting tubules, in the tubular lumen, vascular walls, in the interstitial tissue and cell interstitial infiltrates, on the hypoplastic and disoriented ureteral smooth muscle fibers. The use of the ILIAS-method to determine urinary TGF levels before and after surgery indicated a direct correlation of these indices with the degree of renal tissue dysplasia.     

Effect of citrocard on functional activity of cardiomyocyte mitochondria during chronic alcohol intoxication

Chronic administration of 50% ethanol in a dose of 8 g/kg produces a toxic effect on functional activity of cardiomyocyte mitochondria, which manifested in decreased rates of respiration and oxidative phosphorylation. Structural GABA analogue Citrocard (phenibut citrate) and reference preparation piracetam in doses of 50 and 200 mg/kg, respectively, prevented the damaging effect of alcohol, which was seen from increased indexes of oxidative phosphorylation in treated animals compared to the control group. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 3, pp. 312–314, March, 2007     

Evaluation of magnetic resonance imaging characteristics of new nitroxyl radicals on the model of RLS lymphoma

Toxic and magnetic resonance contrast characteristics of new nitroxyl radicals Fur-135 and Fur-176 were studied in experiments on mice. The test compounds exhibited low toxicity and allowed us to increase contrasting of transplanted RLS lymphoma. Fur-135 differs by the type of contrasting from Gd³⁺-containing preparation omniscan and locates the tumor focus with high precision. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 2, pp. 202–205, February, 2007     

Effect of poplar-type propolis on oxidative stability and rheological properties of O/W emulsions

Propolis is known to possess antioxidant activity. However, there is no information on this activity in emulsions O/W. The protective effect of propolis on the oxidation and rheological properties of emulsions O/W containing wheat germ and almond oils was evaluated. Emulsions O/W were prepared with different concentration of propolis extract, almond oil and wheat germ oil. All emulsions physically stable without phase separation were stored at 37?°C for 9?weeks. Chemical composition of propolis was established by Gas chromatography coupled to mass spectrometry. Rheological characterization of different emulsions was performed evaluating consistency index and flow behavior index. The oxidation was monitored by measuring the lipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS) methods. Flavonoids, phenolic acid esters, and aromatic acids were the main groups of compounds found in propolis. The results showed that popolis was good antioxidant in the concentration of 0.02 and 0.04% when lipid phase was constituted by almond oil. The rheological behavior is typical of a non-Newtonian fluid, being almond oil more adequate for having a higher stable O/W emulsion.     

ON-OFF Interactions in the Retina: Role of Glycine and GABA

In the vertebrate retina, visual signals are segregated into parallel ON and OFF pathways, which provide information for light increments and decrements. The segregation is first evident at the level of the ON and OFF bipolar cells and it apparently remains as signals propagate to higher brain visual centers. A fundamental question in visual neuroscience is how these two parallel pathways function: are they independent from each other or do they interact somehow? In the latter case, what kinds of mechanisms are involved and what are the consequences from this cross-talk? This review summarizes current knowledge about the types of interactions between the ON and OFF channels in nonmammalian and mammalian retina. Data concerning the ON-OFF interactions in distal retina revealed by recording of single bipolar cell activity and electroretinographic ON (b-wave) and OFF (d-wave) responses are presented. Special emphasis is put on the ON-OFF interactions in proximal retina and their dependence on the state of light adaptation in mammalian retina. The involvement of the GABAergic and glycinergic systems in the ON-OFF crosstalk is also discussed.     

Characterization of a Novel SARS-CoV-2 Genetic Variant with Distinct Spike Protein Mutations

The COVID-19 pandemic, which began in Wuhan (Hubei, China), has been ongoing for about a year and a half. An unprecedented number of people around the world have been infected with SARS-CoV-2, the etiological agent of COVID-19. Despite the fact that the mortality rate for COVID-19 is relatively low, the total number of deaths has currently already reached more than three million and continues to increase due to high incidence. Since the beginning of the pandemic, a large number of sequences have been obtained and many genetic variants have been identified. Some of them bear significant mutations that affect biological properties of the virus. These genetic variants, currently Variants of Concern (VoC), include the so-called United Kingdom variant (20I/501Y), the Brazilian variant (20J/501Y.V3), and the South African variant (20H/501Y.V2). We describe here a novel SARS-CoV-2 variant with distinct spike protein mutations, first obtained at the end of January 2021 in northwest Russia. Therefore, it is necessary to pay attention to the dynamics of its spread among patients with COVID-19, as well as to study in detail its biological properties.     

Transgenic angiotensin-converting enzyme 2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function

Rat models of hypertension, eg, spontaneously hypertensive stroke-prone rats (SHRSP), display reduced angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression compared with control animals. The aim of this study was to investigate the role of ACE2 in the pathogenesis of hypertension in these models. Therefore, we generated transgenic rats on a SHRSP genetic background expressing the human ACE2 in vascular smooth muscle cells by the use of the SM22 promoter, called SHRSP-ACE2. In these transgenic rats vascular smooth muscle expression of human ACE2 was confirmed by RNase protection, real-time RT-PCR, and ACE2 activity assays. Transgene expression leads to significantly increased circulating levels of angiotensin-(1-7), a prominent product of ACE2. Mean arterial blood pressure was reduced in SHRSP-ACE2 compared to SHRSP rats, and the vasoconstrictive response to intraarterial administration of angiotensin II was attenuated. The latter effect was abolished by previous administration of an ACE2 inhibitor. To evaluate the endothelial function in vivo, endothelium-dependent and endothelium-independent agents such as acetylcholine and sodium nitroprusside, respectively, were applied to the descending thoracic aorta and blood pressure was monitored. Endothelial function turned out to be significantly improved in SHRSP-ACE2 rats compared to SHRSP. These data demonstrate that vascular ACE2 overexpression in SHRSP reduces hypertension probably by locally degrading angiotensin II and improving endothelial function. Thus, activation of the ACE2/angiotensin-(1-7) axis may be a novel therapeutic strategy in hypertension.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Changes in ECG,plasma and myocardial lipids in experimental myocardial hypertrophy in rats

Summary ECG, systolic blood pressure (BP), the ratio (R) of grams of myocardial mass/100 g of body mass, total lipids, cholesterol, triglycerides and phospholipids in blood plasma and the left ventricular myocardium, as well as the plasma free fatty acids, were investigated in 58 male Wistar rats 3,30 and 180 days after operation, in a model of myocardial hypertrophy (MH) induced by experimental coarctation hypertension, after the method of Sclye.An attempt was made to correlate some functional and metabolic indices which characterize the development of this type of MH. On a background of progressively rising BP and parallel increasing R, ECG change were recorded. They were typical of the respective stage of arterial hypertension and MH and expressed mostly in a shifting of the electrical axis of the heart to the left and in essential repolarization disturbances. The most significant changes in the studied lipid fractions were found 30 days after the induction of hypertension. The pathological changes manifested on the 180th day are discussed in relation to age, the stage of hypertension and especially in relation to the developing hypoxic and ischaemic myocardial damage.     

On Secondary Patenting of Organic Compounds Suitable for use as Active Pharmaceutical Ingredients

Pharmaceutical Chemistry Journal - Secondary patenting of organic compounds that can undoubtedly be used as active pharmaceutical ingredients (APIs) is discussed. As a rule, such compounds, their...