The role of age-related and adaptive changes in the vascular wall in atherogenesis in light of the theory of Academician I. V. Davydovski? on atherosclerosis

Aorta and coronary arteries (1053 and 386 cases, respectively) were evaluated in young persons. It is shown that atherosclerotic developments in the vessels are largely determined by hyperplastic involvement of the intima due to age-related vascular rearrangement and the hemodynamic factor. For aorta, these are represented by rhythmic structures which seem to give rise to the majority of the fibrous plaques. The findings are in consistence with I. V. Davydovsky's conceptions on age-related and adaptation changes in the vascular wall emerging during various human vital activities and supposed to underlie the development of atherosclerosis.     

Role of proliferation and differentiation of hemopoietic precursors in regeneration of hemopoiesis in cytostatic myelodepressions

Quantitative and qualitative composition of hemopoietic tissue and the intensity of proliferation and differentiation of committed hemopoietic precursors are studied in mice treated with adriamycin, cyclophosphane, or 5-fluorouracil. It is shown that intense maturation of colony-forming units results in rapid regeneration of hemopoiesis even under conditions of reduced proliferation of these cells, whereas inhibition of their differentiation suppresses restoration of bone marrow cellularity despite intense proliferation of hemopoietic precursors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 12, pp. 616–620, December, 1997     

Changes in myocardial metabolism and ultrastructure of myocardial microvessels during pharmacological and cold cardioplegia under hypothermic conditions without perfusion

A combination of pharmacological and cold cardioplegia in with hypothermia without perfusion in open-heart surgery guarantee the reversible character of shifts in energy and free radical balance in the myocardium. However, this procedure can impair coronary micricirculation due to structural and functional changes in microvessel endothelium. Our results demonstrate that new cytoprotective approaches are extremely needed for cardiac protection during surgery.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial

BACKGROUND: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 proteinuric patients without diabetes from our outpatient renal clinic. INTERVENTION: Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. OUTCOMES & MEASUREMENTS: Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d-glucosaminidase (NAG) as a positive control for tubular injury. RESULTS: Mean baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706 +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. LIMITATIONS: Post hoc analysis. CONCLUSIONS: Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.     

Management of nucleus and IOL drop

Background: Thirty six cases of lenticular nucleus drop following phacoemulsification and 43 cases of posterior dislocation of intraocular lens (IOL) inclusive of two paediatric cases were managed by a modified vitrectomy procedure without using perfluorocarbon liquid (PFCL).     

Imaging of neurosphere oxygenation with phosphorescent probes

Multicellular spheroids are useful models of mammalian tissue for studies of cell proliferation, differentiation, replacement therapies and drug action. Having a size of 100–500 μm they mimic in vivo micro-environment and characteristic gradients of O₂, pH and nutrients. We describe the use of cell-penetrating O₂ probes based on phosphorescent Pt-porphyrins to perform high-resolution 2D and 3D mapping of O₂ in spheroid structures by live cell fluorescence imaging technique. Optimised procedures for preparation of neurospheres from cortical neural cells isolated from embryonic rat brain, their staining with the phosphorescent O₂ probes NanO2 and MM2 and subsequent analysis of oxygenation on different live cell imaging platforms, including widefield and confocal phosphorescence lifetime imaging microscopy (PLIM), conventional confocal and two-photon ratiometric intensity based O₂ detection are presented. This is followed by a series of physiological experiments in which oxygenation patterns of the neurospheres are correlated with culturing conditions (atmospheric hypoxia and hyperoxia, size, growth factors), distribution of stem cells, mature neurons and astrocytes, HIF-2α stabilisation and responses to metabolic stimulation. The O₂ imaging method allows multiplexing with many conventional fluorescent probes to perform multi-parametric imaging analysis of cells in 3D microenvironment. It can be applied to other types of spheroids and 3D tissue models.