Vascular endothelial growth factor in dialysate in relation to intensity of peritoneal inflammation.

BACKGROUND: Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution. METHODS: Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (microg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected. RESULTS: LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/microL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-alfa, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2+/-5.9; LPS 0.01, 38.9+/-11.6; LPS 0.1, 43.0+/-5.9; LPS 1.0, 46.6+/-11.3; Control, 14.5+/-9.8; p<0.0005 for all LPS vs. Control). CONCLUSIONS: The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV. LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-alfa, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.

Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population.

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the mechanism of action of tricyclic antiderpressants.

In the course of investigations on experimental arterial hypertension in rats, it has been stated, that imipramine prevents the development of hypertension and that is simultaneously causes an accumulation of cAMP in the vessel walls. The relationship between the two phenomena has been discussed.

Atrial natriuretic factor in untreated hyperthyroidism.

Increased plasma concentration of atrial natriuretic factor (ANF) in untreated hyperthyroid patients is reported. A significant positive correlation between the concentration of ANF and serum thyroid hormones (T4 and T3) has been found when hyperthyroid patients and healthy controls were pooled together. The mechanism by which thyroid hormones raise plasma ANF concentration and its relevance to the symptomatology of hyperthyroidism is discussed.

Physiological significance of increased levels of endogenous atrial natriuretic factor in human acute renal failure.

In twelve patients with acute renal failure, mean plasma levels of atrial natriuretic factor (ANF) and of its second messenger cGMP were found elevated at the early phase of the disease, but tended to return towards normal values at recovery. Variations of plasma ANF and cGMP were correlated significantly (p less than 0.05) with those of total blood volume. At the early phase of the disease, plasma ANF was also correlated with the excreted fraction of filtered sodium (FENa) (r = 0.95). Moreover, plasma ANF and FENa peaked concomitantly at the onset of the diuretic phase in the five patients who were not treated by diuretics or dialysis and were studied sequentially during the course of the disease. It is suggested that enhanced plasma ANF levels might reflect one of the mechanisms of adaptation controlling body fluid balance in acute renal failure.

Thyroid function in patients with acute renal failure.

Thyroid function was evaluated in a group of 36 patients with acute renal failure (ARF) during the oliguric/anuric, polyuric and postpolyuric phase. Serum thyroxine (T4) and triiodothyronine (T3) concentrations were significantly decreased in the oliguric/anuric phase, as compared with the mean values obtained in the post-polyuric phase and with controls. In contrast to T3 and T4, the concentration of serum reverse triiodothyronine (rT3) was elevated in the oliguric/anuric phase and normal in the polyuric phase. The sephadex-T3-binding index (T3I) was significantly increased in oliguric/anuric patients and in the polyuric phase. The levels of serum thyreotropin were significantly elevated during all phases of ARF as compared with the controls. From the results obtained it is concluded that abnormal peripheral metabolism of T4 seems to be the primary cause of altered plasma concentrations of thyroid hormones in patients with ARF.

Acute and chronic urinary tract infections caused by Chlamydia trachomatis.

Chlamydia trachomatis is one of the causes of acute and chronic urinary tract infections and acute or silent salpingitis. Chronic or recurrent female urinary or genital tract infections with Chlamydia trachomatis have been recognised as a significant factor in the development of acute or chronic renal interstitial inflammation or increased risk of ectopic pregnancy. In most cases Chlamydia trachomatis is sexually transmitted. Moreover, it is one of the most common sexually transmitted pathogens. The current estimate is that in the United States there occur 4.5 million new infections each year. We describe 3 cases of recurrent urinary tract infections due to Chlamydia trachomatis.

Effect of atropine on plasma atrial natriuretic peptide concentration in healthy subjects.

This work shows that an intravenous infusion of atropine increases the concentration of atrial natriuretic peptide (ANP) in the plasma of healthy subjects. The effect is discussed in reference to the heart rate and the role of the autonomic nervous system in the control of ANP secretion by atrial cardiocytes.

[Frequency of thyroid enlargement (goiter) in residents of the Szczecin region]. / Czestosc wystepowania powiekszenia tarczycy (wola) u mieszkanców regionu szczecinskiego.

The study has been carried out on 4,565 persons (2,349 girls and women also 2,216 boys and men) aged 4-64. The examined group was chosen randomly, according to a simple drawing scheme. The aim of the study is to evaluate frequency, magnitude and character of goiter in residents in Szczecin region. The goiter has been found in 19.5% persons in examined population, so it makes possible an endemic state. In consideration of a fact that goiter appears frequently among women and there are more cases of thyroid enlargement (O-B and I degree), as well as a small number of people with disturbance thyroid function only slightly endemic character is stated. Because the frequency of modular goiter among people with goiter is 20% it doesn't express extent of endemic state.

[Post-transplant nephropathy and arterial hypertension]. / Nadcisnienie tetnicze a przewlekla nefropatia potransplantacyjna.

The introduction of new immunosuppressive regimens results in the significant improvement in the outcome of patients after kidney transplantation. However, about 5 percent of renal transplants are lost every year. Not only immunological (alloantigendependent) but also nonimmunological (alloantigen-independent) factors are involved in late graft loss. Among them, hypertension, hyperlipidemia, proteinuria, genetic predisposition, viral infection and nephrotoxicity of immunosuppressive drugs contribute to the development and to the progression of chronic post-transplant nephropathy. Hypertension can be both the cause and the consequence of chronic allograft failure. Hypertension is frequently observed before transplantation, persists after grafting and increases the risk of chronic allograft nephropathy. Hypercholesterolemia, obesity, atheromatosis, polycythemia, and excessive salt intake are factors contributing in post-transplant hypertension. However, in some cases, hypertension can be transferred with the grafted kidney, as observed in normotensive patients before renal transplantation. In 1 to 12 percent of cases, the cause of post transplant hypertension is the stenosis of the transplant artery. Sometimes the presence of hypertension in renal recipients may result from the recurrence of glomerulonephritis or from the development of glomerulonephritis de novo in the graft. Also immunosuppressive treatment with corticosteroids and cyclosporine A contributes to the increased prevalence of hypertension by 20-30 percent. The development of the graft nephroarteriolosclerosis as a consequence of hypertension accelerates the progression of the post-transplant nephropathy. Adequate control of the arterial pressure (< 140/90) should be achieved in all renal transplant recipients. Reduction in protein and salt intake is important to reduce hyper-filtration and slows the progression of transplant nephropathy. However, pharmacological treatment is usually needed. Angiotensin-converting-enzyme inhibitors, angiotensin II type I receptor antagonists exhibit beneficial hemodynamic effect leading to the reduction of glomerular hypertension and proteinuria. Calcium antagonists besides their systemic antihypertensive effect, can protect renal grafts from vascular and renal toxicity of CyA. Sometimes, combined therapy with these and other antihypertensive drugs and diuretics is necessary.

[Controversial opinions regarding the role of Bcml vitamin D receptor gene polymorphism on parathyroid function, calcium absorption and bone mineral density in persons with normal renal function and patients with chronic renal failure]. / Kontrowersje w opiniach oceniajacych wplyw polimorfizum Bsml genu receptora witaminy D na czynnosc przytarczyc, wchlanianie wapnia i gestosc mineralna kosci u osób z wydolnymi nerkami i chorych na przewlekla niewydolnosc nerek.

This paper summarizes current, but controversial opinions of different authors evaluating the effect of Bsml polymorphism of the vitamin D receptor gene on the parathyroid function, calcium absorption from the digestive tract and bone mineral density (BMD) in persons with normal renal function and in patients with chronic renal failure. On the basis of these data, the recapitulation of the prevailing opinions was undertaken. Contemporary it is admitted, that the persons with bb genotype and normal renal function are at risk for the development of the parathyroid adenomas while in the patients with chronic renal failure the bb genotype may favour parathyroids hyperplasia. It is also believed that bb genotype in the persons with normal renal function facilitates calcium absorption and is associated with greater BMD. Few investigations performed in the patients with chronic renal failure suggest that the BB genotype may partially influence lower BMD in the subgroup of younger patients treated with hemodialysis for a relatively short period. Existing controversies need however further clarification.

[The evaluation of bone mineral density and selected markers of bone turnover in patients with insulin dependent diabetes mellitus]. / Ocena gestosci mineralnej kosci i wybranych markerów przebudowy kosci u chorych na cukrzyce insulinozalezna.

The aim of study was to evaluate bone mineral density (BMD) in lumbar spine (AP Spine), total body (Total Body) and distal site of radius (Forearm), and selected markers of bone formation: serum alkaline phosphatase (ALP) and osteocalcin(OC), and bone resorption: pyridinoline (PIR) and deoxy-pyridinoline (DPIR) in urine, in patients with long-standing insulin-dependent diabetes mellitus (IDDM), in comparison to healthy controls. Additionally, the influence of age, sex, smoking, duration of IDDM, the degree of metabolic control, or coexisting chronic complications of diabetes (retinopathy, incipient nephropathy, polyneuropathy) on the studied indices of bone metabolism in patients with IDDM were evaluated. The study was carried on 54 diabetic patients (23 F, 31 M) and 25 healthy individuals (13 F, 12 M). BMD was measured by DEXA (LUNAR DPX-L System). ALP was assessed by enzymatic method, and OC by RIA (Incstar Corporation). PIR and DPIR were assessed by EIA (Metra Biosystems). It was found that patients with long-standing IDDM have significantly lower BMD than healthy controls. The incidence rate of osteopenia and osteoporosis is significantly higher in this group of patients in comparison to the controls. In comparison to healthy subjects, patients with IDDM have significantly higher, but within normal reference range, serum ALP and OC, accompanied by similar PIR and not significantly increased DPIR. Duration and metabolic control of diabetes, or the coexistence of its chronic complications do not correlate with BMD or the studied indicies of bone turnover.

Plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate in patients with hyperthyroidism before and after short-term treatment with methimazole.

The aim of the study was to answer the question whether a rapid decrease in serum triiodothyronine (T3) and thyroxine (T4) levels resulting from the treatment with a full dose (3 x 20 mg daily) of methimazole applied in patients with thyrotoxicosis is associated with the parallel diminution of plasma atrial natriuretic peptide (ANP) and its second messenger-cyclic guanosine monophosphate (cGMP) concentrations. Sixteen patients with thyrotoxicosis of mean age 41.5 +/- 10.5 years participated in the study. Short-term (10 days) methimazole treatment resulted in a significant decrease in serum T3 and T4 concentrations to the values found in 14 healthy subjects serving as control group. Plasma ANP and cGMP levels also decreased significantly during the treatment attaining the normal range. A significant correlation was found between the decrease in serum T3 and T4 concentrations during the treatment and the decrease in plasma ANP level. The decrease in plasma ANP was not closely correlated with the reduction of cGMP levels. These results indicate that: 1) a steep decrease in serum thyroid hormone concentrations induced by a full methimazole treatment during ten days in patients with thyrotoxicosis due to Graves' disease was accompanied by the return of elevated plasma ANP levels to normal range; 2. diminution of serum concentrations of both T3 and T4 during the treatment was correlated with the decrease in plasma ANP; 3) reduction in plasma cGMP concentration associated with short-term methimazole treatment in thyrotoxicosis seems to depend not only on the diminution of plasma ANP level.

[Effect of naloxone on beta-endorphin and insulin concentrations during glucose tolerance testing in patients with simple obesity]. / Wplyw naloksonu na stezenia beta-endorfiny i insuliny w czasie testu doustnej tolerancji glukozy w otylosci prostej.

The concentrations of beta-endorphin, ACTH, insulin (IRI), glucagon (IRG), cortisol and growth hormone were determined by radioimmunoassay during oral glucose tolerance test (OGTT) performed in 13 obese patients with normal glucose tolerance and without arterial hypertension. The test was performed in random, before and after intravenous administration of 0.8 mg of naloxone. Six persons with normal body weight served as controls. Higher basal concentrations of beta-endorphin and significant increase in beta-endorphin levels during OGTT, without concomitant increase in ACTH concentrations, have been found in obese patients. No effect of naloxone on beta-endorphin liberation during OGTT was observed, though the drug caused lowering in maximal increment of beta-endorphin and paradoxically lowered the concentrations of ACTH and cortisol. The basal concentrations of beta-endorphin did not correlate with the concentrations of insulin, ACTH, cortisol and growth hormone. Elevated concentrations of insulin, lowered concentration of growth hormone and normal levels of glucose and glucagon were observed in basal conditions, and excessive responses of insulin, glucose and glucagon were observed in obese patients during OGTT. Naloxone lowered insulin response and inhibited the fall of growth hormone during OGTT but did not influence the concentrations of glucose and glucagon. No correlation was found during OGTT after naloxone between insulin and beta-endorphin, ACTH or cortisol, whereas negative correlation was observed between insulin and growth hormone. The obtained results suggest that the elevated concentrations of beta-endorphin in simple obesity may be of both hypophyseal and peripheral origin. Hyper-beta-endorphinemia observed in obesity is probably not directly responsible for hyperinsulinemia, it may, however, be responsible for lower sensitivity of tissues to the action of insulin.

[Diagnostic value of electrophysiologic studies in diabetics in our experience]. / Wartosc diagnostyczna badan elektrofizjologicznych u cukrzyków w oparciu o doswiadczenia wlasne.

Twenty two patients (44 eyes) with diabetes of the type I aged 18-60 were examined. Duration of diabetes--at least 10 years. Performed were routine ophthalmological, general medical and electrophysiological examinations (EOG, ERG, with registration of oscillatory potentials, visual evoked potentials). It was evidenced that the most accurate method demonstrating the disturbances of the retinal function--independently of the visual acuity, fundus changes and other signs and complications--are the oscillatory potentials. Evoked visual potentials enable us in a majority of cases to evidence the central and subclinical disturbances of the optic nerve.

[Frequency of goiter in children and adolescents in the Szczecin region]. / Czestosc wystepowania wola u dzieci i mlodziezy regionu Szczecinskiego.

The study was carried out in 2153 children and adolescents (1066 girls and 1087 boys) aged 5-20 years. The examined group was chosen randomly, according to a simple drawing scheme. The aim of the study was to evaluate frequency, size and character of goiter in developmental age population in Szczecin's region. The goiter was found in 14% of examined population (18.4% in girls and 9.8% in boys). Frequency of goiter approximated to 37% in girls and 16% in boys during puberty spurt (between 10 and 16 year of age). Small degree of thyroid enlargement was predominant in examined population. Large goiter was present more frequent in girls than in boys. We did not find clinical symptoms of thyroid gland dysfunction in examined group. Frequency of nodular goiter was 7% of children's and adolescent's population with higher incidence in boys (9%) than in girls (6%).

[Analysis of early results of combined treatment with glucocorticoids and telecobalt therapy for Graves' disease ophthalmopathy]. / Ocena wczesnych wyników skojarzonego leczenia glukokortykoidami i telekobaltoterapia postepujacej oftalmopatii obrzekowo-naciekowej w chorobie Graves-Basedowa.

Early results of combined use of glucocorticoid administration and irradiation with radioactive cobalt for treatment of oedematous-infiltrative ophthalmopathy associated with Graves' disease have been analyzed in a group of 33 patients including 28 women and 5 men of age between 25 and 66 years (mean age 47.3 years). The combined therapy was a modification of the original method of Bartalena et al. which consisted in the gradual increase of the initial dose of glucocorticoids and prolongation of the period of administration of the drug. The ophthalmic lesions were assessed by thorough ophthalmologic examination and classified according to Werner. The ophthalmopathy index was calculated according to Donaldson. Satisfactory results of treatment have been obtained in 32 patients, with 9 patients being completely relieved from any objective or subjective ophthalmic symptoms (very good results), and 23 patients having still small afflictions originating from the soft tissues of the eye socket, exophthalmos, diplopia during marginal vision and a decreased visual acuity (good results). The clinical recovery was mostly connected with the improvement in the condition of soft tissues of the eye socket, cornea and external ocular muscles and, to a smaller extent, exophthalmos which persisted to some degree and acuity of vision not always attaining normal values. In one person the results of treatment were unsatisfactory despite some improvement. Very good and good results obtained in 97% of patients indicate that the administration of glucocorticoids combined with the irradiation of retrobulbar tissues with radioactive cobalt can now be regarded as the most effective method of treatment of the progressive oedematous-infiltrative ophthalmopathy.

Iodized salt consumption, urinary iodine concentration and prevalence of goiter in children from four districts of north-western Poland (Szczecin coordinating center).

The study was aimed at evaluation of iodized salt consumption, urinary iodine concentration and incidence of goiter in children from four districts of north-western Poland: Szczecin, Koszalin, Slupsk and Gorzów Wlkp. The study was a part of the national programme: "Investigations of iodine deficite and iodine prophylaxis in Poland". The investigations were performed in ten schools randomly selected by Coordinating Centre in Kraków. Altogether 1793 children attending these schools (838 boys and 955 girls) of age between 6 ad 13 years, living in the cities and villages of coastal and lowland region were studied. The examination included interview in the form of a standard questionnaire, physical examination of the thyroid according to the WHO criteria, ultrasonographic evaluation of thyroid volume and determination of iodine concentration in single urine specimen. It appeared that only 11.2% of children used to consume iodized salt. Mean iodine concentration in urine was 76.2 micrograms/l both in children consuming and not consuming iodized salt, indicating dietary iodine deficiency. The incidence of goiter in country population of children (12.9%), indicated that the region of north-western Poland should be considered as an area of mild goiter endemy. These results suggest a need for iodine supplementation of edible salt in this region of Poland.