The functional kidney reserves of diabetics

Ten patients with insulin-dependent diabetes mellitus not associated with any signs of diabetic nephropathy were examined for the reserves of filtration renal function and early morphological alterations in organ tissues. The reserves of filtration were detected under the conditions of acute oral administration of protein (1.5 g/kg) as difference between the initial and stimulated levels of glomerular filtration (GF). Two groups of patients were distinguished: group I included patients with preserved filtration reserves (increment of GF amounted to 35%), group II included patients with no filtration reserves (reduction of GF was 20%). Both the groups differed significantly only in the initial level of GF (120 and 209 ml/min, respectively) and in the degree of morphological changes in the glomeruli: group I manifested minimum structural changes, group II showed the commencing diabetic glomerulosclerosis characterized by pronounced injury to the manubrium of the glomeruli. Therefore, the lack of filtration reserves in diabetes mellitus patients suggests the presence of the commencing diabetic glomerulonephritis even with the lack of the clinical signs of renal injury, which does not require the resorting to organ biopsy. The primary injury to the manubrium of the glomeruli is likely to be related to a high gradient of intraglomerular hydrostatic pressure, resulting in hyperfiltration.     

Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1

Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = ?0.81); most patients with low-medium (39–55) repeat numbers survived until the end of reproductive age. The number of CAG repeats expands in meiosis, particularly in paternal transmissions; the average total increase in intergenerational transmissions in our cohort was estimated at 1.6 CAG repeats. The fertility rates of heterozygous carriers of 39–55 CAG repeats in women were no different from those of the general Sakha population. Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels. The low (0.19) Crow’s index of total selection intensity in our SCA1 cohort implies that this mutation is unlikely to be eliminated through natural selection alone.     

A20 deficiency in B cells enhances B-cell proliferation and results in the development of autoantibodies

A20/TNFAIP3 is an ubiquitin-editing enzyme, important for the regulation of the NF-κB pathway. Mutations in the TNFAIP3 gene have been linked to different human autoimmune disorders. In human B-cell lymphomas, the inactivation of A20 results in constitutive NF-κB activation. Recent studies demonstrate that in mice the germline inactivation of A20 leads to early lethality, due to inflammation in multiple organs of the body. In this report, we describe a new mouse strain allowing for the tissue-specific deletion of A20. We show that B-cell-specific deletion of A20 results in a dramatic reduction in marginal zone B cells. Furthermore, A20-deficient B cells display a hyperactive phenotype represented by enhanced proliferation upon activation. Finally, these mice develop higher levels of serum immunoglobulins, resulting in an excessive production of self-reactive autoantibodies.     

Deficit of Neurotrophins in Experimental Diabetes – Correction with a Proline-Containing Dipeptide

Neuroscience and Behavioral Physiology - Experiments on Wistar rats using a model of type 2 diabetes induced by streptozotocin (STZ) at a dose of 40 mg/kg addressed the effects of the...     

Low doses of recombinant erythropoietin in the treatment of renal anemia in patients on chronic hemodialysis and ambulatory peritoneal dialysis]

AIM: A comparative study of efficiency and safety of low-dose erythropoietin (EP) in two groups of patients with chronic renal failure (CRF): patients on chronic hemodialysis (CHD) and patients on continuous ambulatory hemodialysis (CAHD). MATERIALS AND METHODS: 51 CRF adult patients with renal anemia on hemodialysis entered the trial: 34 CHD and 17 CAHD patients. EP compounds were injected s.c. in a dose 1000-2000 U 2-3 times a week. RESULTS: EP treatment provided a rapid correction of renal anemia in the majority of patients. After 3-month EP therapy a mean increment of Hct (Hct delta) was much greater (p < 0.05) in CAHD than CHD patients (12.2 +/- 6.0 and 9.0 +/- 5.1%, respectively), though EP dose were the same in both the groups. CONCLUSION: Low doses of recombinant human EP injected subcutaneously were effective and safe for correction of anemia in both CHD and CAHD. In CAHD patients EP effectiveness was much higher than in CHD patients.     

Cortical connectivity during word association search.

Cortical connectivity was studied in tasks of generating the use of words in comparison with reading aloud the same words. These tasks were used earlier in PET and high density ERP recordings studies (Posner and Raichle, 1997; Abdullaev and Posner, 1998), in which both the functional anatomy and the time course of cortical areas involved in word processing were described. The wavelet transforms of ERP records and the calculation of correlations between wavelet curves were used to reveal connections between cortical areas. Three stages of intracortical communications while task performance were found. These were: (1) the connections between right and left frontal and central areas which preceded stimulus delivery and persisted up to 180 ms after it; (2) the network connecting right and left frontal with left posterior temporal-parietal junction at 280-450 ms; and (3) communications between left and right temporal zones in 550-800 ms. The data are in good agreement with results of previous PET and ERP studies and supply the earlier findings with circuitry of cortical information transfer.