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Biomedical subjects

I I Dedov

Publications and source records attributed to I I Dedov.

At least 37 records · Page 2Linked to original sources

[Diabetic nephropathy: risk factors of rapid progression of renal failure].

AIM: To reveal factors accelerating development of chronic renal failure (CRF) in patients with insulin-dependent diabetes mellitus type I (DM-I). MATERIALS AND METHODS: A retrospective analysis of case histories was made for 40 patients with DM-I exhibiting progression of proteinuric stage of diabetic nephropathy prior to CRF stage. Clinical-laboratory indices were compared for patients with slow (group 1, n = 17) and fast (group 2, n = 23) development of CRF. RESULTS: Patients of group 2 had significantly higher levels of glycosylated hemoglobin, total cholesterol, triglycerides in the blood, urine protein excretion, systolic and diastolic blood pressure than patients of group 1. Also, patients of group 2 had not taken antihypertensive drugs regularly. CONCLUSION: Factors of risk of CRF early development of DM-I patients comprise unsatisfactory compensation of carbohydrate metabolism, hyperlipidemia, high proteinuria, arterial hypertension and inadequate antihypertensive therapy.

Adolescent↗

[Polymorphism of gene encoding vascular angiotensin II receptor and microangiopathies in patients with insulin-dependent diabetes mellitus].

Polymorphism A1166C of the AT1R gene encoding angiotensin vascular receptor [replacement of C (cytosine) for A (adenine)) at position 1166] was compared in patients with insulin-dependent diabetes mellitus (IDDM) complicated by diabetic nephropathy (DN) and in noncomplicated patients (n = 27 and n = 41, respectively) and also in patients with IDDM complicated by diabetic retinopathy (DR) and in correspondent noncomplicated individuals (n = 30 and n = 44, respectively). The frequency of AT1R gene alleles and genotypes in patients with IDDM complicated by DN did not differ significantly from that observed in patients with noncomplicated IDDM. In contrast, in patients with IDDM complicated by retinopathy, a significant decrease in the content of A allele (68.3% against 82.6%) and a significant increase in the content of C allele (31.7% against 17.4%) was found as compared with the control group. Thus, in the Moscow population, A1166C polymorphism of the AT1R gene is not associated with diabetic renal complications but indeed associated with diabetic retinal complications. C allele is a risk factor of DR (the relative risk, RR, is equal to 2.17), and A allele is, in contrast, a protective factor against early retinopathy development (RR is equal to 0.49).

Adolescent↗

[Sildenafil citrate (viagra) treatment in patients with diabetes mellitus].

AIM: To evaluate different dosages of vasoactive drug viagra in patients with erectile dysfunction suffering from diabetes mellitus (DM) type I and II. MATERIALS AND METHODS: Viagra in doses 25, 50 and 100 mg was given to 30 DM patients with different forms of erectile dysfunction. RESULTS: The response was obtained in 70.3% of cases. The highest effect was achieved with the dose 100 mg (the response rate 68.5% of patients). The dose 50 mg was effective in 31.5%, 25 mg in 0% of patients. Most nonresponders had low testosterone levels in the blood.

3',5'-Cyclic-GMP Phosphodiesterases↗

Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency.

To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.

Adolescent↗

A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD), including growth hormone (GH), prolactin (Prl) and thyroid-stimulating hormone (TSH) in children is now considered a heterogeneous syndrome. Recent findings on expression of mouse pituitary-specific homeodomain factors demonstrate dependence of adenopituitary ontogeny on interactive expression of these factors, suggesting their involvement in etiology of CPHD. Prophet of Pit-1 (Prop-1) gene, a novel pituitary-specific homeodomain factor, was analyzed in 14 Russian children with CPHD, in whom Pit-1 gene was intact. We found a mutational hot spot in three patients from two families in homeodomain part of the second exon of Prop-1 gene. The common 2-base pair deletion (GA296) in the homozygous state resulted in a Serine to Stop codon (S109X) substitution and generated a truncated Prop-1 protein. Parents were phenotypically normal and heterozygous for GA296 deletion, indicating an autosomal recessive inheritance. These results demonstrate a novel type of Prop-1 gene mutation as one of the causes of CPHD in Russian patients.

Amino Acid Sequence↗

Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.

Mutations in the prophet of Pit-1 gene (PROP1) have been shown to be responsible for combined pituitary hormone deficiency (CPHD) with deficiencies of growth hormone (GH), Prolactin (Prl), thyroid-stimulating hormone (TSH) and gonadotropins. We previously reported that homozygosity for a 2bp deletion in exon 2 (296delGA) accounted for CPHD in three patients from two Russian families. Here we report a second mutational hot spot in exon 2. This 2bp 149delGA deletion results in a frame shift that leads to the same serine to stop codon change at codon 109 (S109X). The predicted proteins are each truncated at residue 108 but diverge from the wild type sequence at different points in the homeodomain. Compound heterozygosity for the two mutations (149delGA/296delGA) was detected in 5 of 14 CPHD children from 4 families (36%). This provides the first evidence of heterozygosity for two common deletions as a cause of CPHD in Russian children.

Adolescent↗

[The efficacy of Sulodexide--a low-molecular heparin--in the therapy of diabetic nephropathy].

A novel pathogenetic approach to treatment of diabetic nephropathy (DN) as a severe complication of diabetes mellitus is aimed at inhibiting DN progression or its involution by means of reestablishment of heparan sulfate synthesis by glycosaminoglycane drug. In the study of 9 patients with microalbuminuria and 9 with proteinuria this drug was low-molecular heparin-sulodexide (Alfa-Wasserman, Italy). The treatment course of 3 weeks resulted in albuminuria fall in 89% of patients. In patients with microalbuminuria protein excretion returned to normal values in a week of treatment. This effect was persistent after the drug discontinuation. This was not so for protein excretion in proteinuria patients which became low after 3 weeks of treatment, but the effect was not long-lasting. The authors believe that glycosaminoglycanes hold great promise in DN, especially at early stages of renal diabetic affection.

Adolescent↗

[Vasoactive factors of the vascular endothelium in patients with non-insulin-dependent diabetes mellitus and kidney involvement].

To evaluate the secretion of vasoactive factors in vascular endothelium of patients with non-insulin-dependent diabetes mellitus (NIDDM) the authors examined 31 NIDDM patients. Of them, 18 had no signs of renal involvement, 13 patients showed apparent diabetic nephropathy (DN). In the former patients the blood contained much greater content of vasodilating factor prostacyclin than of vasoconstricting factor endothelin-1 (ET-1) and thromboxan A2 (TxA2). In diabetic nephropathy the balance of vasoactive factors shifted to predominance of vasoconstrictors ET-1 and TxA2. Such rearrangement of vasoactive factors to higher quantities of vasoconstrictors in diabetes mellitus may initiate or promote progression of diabetic nephropathy with resultant spasm of afferent glomerular vessels, reduced glomerular filtration and renal blood flow rates, arterial hypertension, increased thrombogenesis. Thus, elevated levels of ET-1 and TxA2 in diabetics and their rise with progression of diabetic nephropathy are likely to act as pathogenetic factors underlying onset and progression of nephroangiopathy.

Albuminuria↗

[The thromboxane-synthesis inhibitor Ibustrin in the treatment of diabetic angiopathies].

16 patients with insulin-dependent diabetes mellitus (IDDM) lasting 8-19 years had pronounced diabetic nephropathy (proteinuria stage), retinopathy (stage I, II or III), disturbed circulation in the lower limbs detected at foot dopplerography. For 3 months these patients received ibustrin (inhibitor of cyclooxigenase, blocker of tromboxane A2 synthesis and platelet aggregation) before renal function underwent positive changes: glomerular filtration rate increased in 13 patients (81%), 24-h proteinuria decreased in 12 patients (75%). Retinal vascular condition improved in 5 of 6 patients with nonproliferative retinopathy and in 2 of 5 patients with preproliferative retinopathy, in 1 and 3 patients stabilization occurred, respectively. In proliferative retinopathy improvement and stabilization were registered in 1 and 3 of 5 patients, respectively. According to feet artery dopplerography the improvement, no changes and moderate aggravation occurred in 10(62%), 3(19%) and 3(19%) of patients, respectively The conclusion is made that ibustrin effectively inhibits progression of IDDM vascular complications, especially at early angiopathy stages.

Adolescent↗

[Endothelial relaxation factor in the development of diabetic nephropathy].

Progression of diabetic nephropathy is now associated with intrarenal hemodynamic disorders (renal hyperperfusion, hyperfiltration, intraglomerular hypertension). The cause of these disorders is unclear. It is supposed that the relaxation factor which is produced by the vascular endothelium (endothelial relaxation factor-ERF) and an endogenous nitrogen oxide (NO) can cause the above intrarenal hemodynamic alterations in diabetes mellitus. The production of ERF/NO in 35 patients with insulin-dependent diabetes mellitus who had varying severities of diabetic nephropathies were examined. These included the following groups: 1) patients without diabetic nephropathy (n = 9); 2) those with incipient diabetes mellitus (n = 12), 3) those with severe diabetes mellitus (n = 14). From groups 1 and 2, 5 patients with hyperfiltration were identified, their glomerular filtration rate were more than 140 ml/ml. The ability of the cells to produce ERF/NO was indirectly estimated, by determining the levels of human platelet guanylate cyclase in the presence of L-arginine, a NO precursor, the accumulation of cGMP in the cells and plasma. When L-arginine was present, the activity of guanylate cyclase was virtually unchanged in Group 1, but it was substantially increased in Groups 2 and 3, by reaching its peak in patients with hyperfiltration (Group 4). The platelet and plasma levels of cGMP corresponded to the enhancement of guanylate cyclase activity in the presence of L-arginine and increased as diabetic nephropathy progressed. Thus, it is suggested that there is ERF/NO hyperproduction in patients at a high risk for diabetic nephropathy (those having hyperfiltration). ERF/NO is likely to promote the dilation of glomerular arterioles, which results in the development of hyperfiltration and intraglomerular hypertension, causing diabetic nephropathy progression.

Adolescent↗

Frequency analysis of HLA-DQA1 and HLA-DQB1 gene alleles and susceptibility to type 1 diabetes mellitus in Russian patients.

The HLA-DQA1 and DQB1 genes have recently been recognized to be strong genetic markers of susceptibility to type 1 (insulin-dependent) diabetes mellitus. The Arg52 DQA1 and non-Asp57 DQB1 alleles of these genes correlate with the disease predisposition and the Asp57 DQB1 and non-Arg52 DQA1 alleles with disease protection. We investigated 113 patients with type 1 diabetes and 121 healthy subjects from the Russian population of Moscow using DNA amplification and dot-blot hybridization with sequence-specific oligonucleotides (SSO). Using conventional statistical methods we confirmed previous observations indicating the important role of the above-mentioned amino acid residues in susceptibility and resistance to type 1 diabetes. Relative risk values for all alleles and absolute risk for carriers of most predisposing allele combinations were calculated. The absolute risk for carriers of DQA1 and DQB1 gene alleles allowing for the formation of four possible 'diabetogenic' heterodimers on the surface of immunocompetent cells, regardless of the type of coding (cis or trans), was 2.54%, which is 13 times greater than the background risk for the Russian population--0.2% up to 30 years of age.

Adolescent↗

Effectiveness and cost-benefit analysis of intensive treatment and teaching programmes for type 1 (insulin-dependent) diabetes mellitus in Moscow--blood glucose versus urine glucose self-monitoring.

In a prospective controlled trial the effects of a 5-day in-patient treatment and teaching programme for Type 1 (insulin-dependent) diabetes mellitus on metabolic control and health care costs were studied in Moscow. Two different intervention programmes were compared, one based upon urine glucose self-monitoring (UGSM, n = 61) and one using blood glucose self-monitoring (BGSM, n = 60). Follow-up was 2 years. A control group (n = 60) continued the standard treatment of the Moscow diabetes centre and was followed-up for 1 year. Costs and benefits with respect to hospitalizations and lost productivity (according to average wage) were measured in November 1992 rubles (Rb.), with respect to imported drugs and test strips in 1992 German marks (DM). In the intervention groups there were significant decreases of HbA1 values [UGSM: 12.5% before, 9.4% after 1 year, 9.2% after 2 years (p < 0.0001); BGSM: 12.6% before, 9.3% after 1 year, 9.2% after 2 years (p < 0.0001) compared to no change in the control group (12.2% before, 12.3% after 1 year)], and of the frequency of ketoacidosis. The frequency of severe hypoglycaemia was comparable between the UGSM (10 cases during 2 years), BGSM (10 cases during 2 years), and the control group (8 cases during 1 year).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗