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I Zofková

Publications and source records attributed to I Zofková.

At least 19 recordsLinked to original sources
PubMed2004

Postmenopausal serum androstenedione levels are associated with the calcitonin receptor gene polymorphism T1377c. A pilot study.

We tested the hypothesis that homeostasis of sex-steroids is related to the calcitonin receptor (CALCR) genotype. To determine the CALCR genotype PCR amplification followed by digestion with Alul restriction enzyme were carried out according to Nakamura et al. Indeed, a single nucleotide difference at position 1377 of cDNA generates two alleles (CC genotype or TT genotype). Serum estradiol, testosterone and their precursors androstendione (AD) and DHEA levels were estimated in a cohort of 113 postmenopausal women. While serum DHEA levels did not differ between the individual allele combinations, AD levels as well as AD/DHEA ratio were higher in carriers of TC and CC genotypes than those with TT genotype (p<0.05 and p<0.02, respectively, ANCOVA). We postulate that the 3beta-hydroxysteroid dehydrogenase activity is associated with C allele at least in C19 steroids. The data correspond with the functionality of CALCR.

Alleles↗
PubMed2003

Apolipoprotein E 4 allele is associated with low bone density in postmenopausal women.

Apolipoprotein E (Apo E) genotypes have been associated with a number of involutional disorders. Recently some studies have examined whether the Apo E 4 allele might play a role in the pathophysiology of postmenopausal osteoporosis. However, association analysis between Apo E genotypes, BMD, bone loss or fracture risk have not brought universal findings. The aim of this study was, therefore, to determine the relationship between the presence or absence of Apo E 4 allele and BMD in postmenopausal women of Caucasian origin. We studied 113 women, age 62.5 +/- 8.9 yr, who underwent measurement of hip and spine BMD by dual-energy absorptiometry (DXA, g/cm2). Apo E genotypes were assessed by PCR amplification and by restriction typing with Cfol enzyme. The Apo E allele frequencies in the study population were as follows: E2 0.084, E3 0.845, E4 0.071. Because the Apo E 4 allele was associated with osteoporosis in previous studies, the probands were dichotomized by the presence or absence of Apo E 4 allele. After adjustment for BMI and years since menopause BMD at the lumbar spine varied significantly by Apo E 4 status. Women with Apo E 4 allele had significantly lower BMD at the lumbar spine than women with no Apo E 4 allele (p<0.003, ANCOVA). In contrast, there were no significant differences in BMD at the hip comparing women with or without the Apo E 4 allele. To conclude, these data may support the importance of Apo E 4 allele in determining postmenopausal spine bone mass.

Absorptiometry, Photon↗
PubMed2003

Serum parathyroid hormone levels are associated with FokI polymorphism of the vitamin D receptor gene in untreated postmenopausal women.

BACKGROUND: Allelic variants in polymorphisms of the vitamin D receptor (VDR) gene have been related to the incidence of secondary, as well as primary, hyperparathyroidism. In spite of their pathophysiological importance, the relationships between VDR genotypes and serum PTH regulation in normal women have not been extensively investigated. METHODS: We studied the association between the VDR gene (FokI polymorphism) and serum parathyroid hormone (PTH) levels during the winter in 95 untreated, postmenopausal women with normal values of serum PTH. We checked statistically for years since menopause (YSM) and serum ionized calcium. Intergroup differences in serum PTH levels between FF, Ff, and ff allele combinations of FokI polymorphism were evaluated using a one-way ANCOVA and the least significant difference (LSD) multiple comparisons test. RESULTS: Significant intergroup differences were found in PTH values (P<0.035, ANCOVA), which were higher in the ff than in the FF genotype (P<0.01, LSD). No differences in serum PTH were found between allele combinations in ApaI, TaqI, and BsmI polymorphisms. CONCLUSION: Our findings suggest that the FokI polymorphism of the VDR gene is closely related to the magnitude of PTH secretion and/or degradation in postmenopausal women. The causal importance of this phenomenon in the development of postmenopausal osteoporosis remains to be determined.

Journal Article↗
PubMed2003

Does polymorphism C1377T of the calcitonin receptor gene determine bone mineral density in postmenopausal women?

In a cross-sectional study we investigated the potential association between CALCR polymorphism (C1377T) and bone mineral density in 114 postmenopausal women. T homozygotes had higher BMD (g/cm2) at the femoral neck compared with carriers of C allele (p < 0.02, ANCOVA). Means of BMD at the lumbar spine did not differ among the genotypes (ANCOVA). In conclusion, the CALCR gene is associated with bone mass at the femoral neck in postmenopausal women.

Alleles↗
PubMed2003

A single nucleotide polymorphism under the reverse primer binding site may lead to BsmI mis-genotyping in the vitamin D receptor gene.

UNLABELLED: The BsmI polymorphism in the VDR gene has been extensively investigated by PCR and restriction digestion in bone genetics. A SNP within the corresponding region for the previously published reverse primer was observed and confirmed by DNA sequencing. BsmI mis-genotyping caused by this SNP could confound genetic findings. INTRODUCTION: By analyzing the FokI, BsmI, ApaI, and TaqI polymorphisms in the vitamin D receptor (VDR) gene, we observed a significantly different genotype distribution in the BsmI polymorphic locus with a deviation from Hardy-Weinberg equilibrium. One of the reasons for polymerase chain reaction (PCR) non-amplification may be a mismatched base at the primer binding region. Therefore, the aim of this study was to analyse whether a single nucleotide polymorphism (SNP), which has been recently described as TruI, is responsible for the discrepancy between expected and observed genotype frequencies. MATERIALS AND METHODS: The VDR genotypes were identified in a cohort of 165 peri- and postmenopausal women of white origin. PCR amplification was carried out using the originally published primers and followed by restriction cleavage. The BsmI genotypes were further verified with a reverse primer external to the original binding site. The presence of the TruI polymorphism under the previously published reverse primer was confirmed by a restriction digestion and DNA sequencing. In Bb subjects, the colocalization of b allele with the TruI restriction site on the same chromosome was confirmed by a simultaneous digestion of the PCR product with both BsmI and TruI restriction enzymes. RESULTS: The BsmI reanalysis with an external primer provided a higher number of heterozygous subjects with a proportionally smaller number of BB subjects, and the changed genotype distribution was under Hardy-Weinberg equilibrium (BB, 31; Bb, 80; bb, 54; r = 0.0203; p = 0.90). In our primary analysis, the presence of the TruI polymorphism led to a drop out of b allele during PCR amplification and thus to the false prevalence of BB genotypes (BB, 50; Bb, 61; bb, 54; r = 11.17; p = 0.01). CONCLUSION: The SNP in the region corresponding to the reverse primer may lead to BsmI mis-genotyping, which may have confounded some previous genetic studies.

Alleles↗
PubMed2003

Pathophysiological and clinical importance of insulin-like growth factor-I with respect to bone metabolism.

The modern concept of causality of diseases emphasizes the study of natural defense functions of the organism and possibilities of influencing them, which will lead to effective prevention of these diseases. A great deal of information has been obtained on the system growth hormone (GH)/insulin-like growth factor (IGF)-I, which is of quite fundamental importance for the integrity of the organism. An imbalance of the system may be the cause of diseases of the neonatal period, as well as diseases associated with aging. In old age, the synthesis of the crucial peptide system, IGF-I, declines as well as the sensitivity of tissues to this hormone. At the same time the changes in the expression of IGF-binding proteins (IGFBP) occur. Systemic growth factors are present in measurable concentrations in the circulation, they are, however, taken up or synthesized by some tissues, where they act as local cellular regulators. IGF-I is produced by many tissues, including bones under the control of estrogens, growth hormone and the parathyroid hormone. A decline of bone IGF-I in the cortical portion of bones is one of the many mechanisms leading to the development of involutional osteoporosis. Correlation studies, which have provided evidence of a relationship between the IGF system and the building of peak bone mass and its subsequent loss contributed to the understanding of the pathogenesis of this disease. It may be foreseen that the results of intervention studies focused on the effects of the recombinant IGF-I will also influence therapeutic and preventive approaches. Modern antiresorption pharmacotherapy stabilizes or enhances bone density and reduces the risk of fractures. The addition of effective anabolics might increase the effectiveness of treatment by shifting the remodeling equilibrium in favor of formative processes. Because both recombinant GH and IGF-I have certain therapeutic limitations, it is considered to utilize substances which either stimulate endogenous IGF-I production directly in the bone or modulate synthesis and distribution of binding proteins for the peptide. Further new findings related to physiology and pathophysiology of this peptide will contribute to designing new strategies in the prevention of osteoporosis and other serious diseases of old age, such as diabetes, neoplasias or cardiovascular diseases.

Animals↗
PubMed2002

The estrogen receptor alpha gene determines serum androstenedione levels in postmenopausal women.

Estrogen receptors (ER) are expressed not only in the reproductive system and ovaries but also in some other tissues, including the adrenal gland. The purpose of this study was to assess the association between the estrogen receptor (ER) alpha gene polymorphisms XbaI and PvuII and circulating levels of androstenedione, a precursor of sex-steroids synthetized in the ovary and adrenal. After adjustment for years since menopause, body mass, and dehydroepiandrosterone (DHEA) levels, a highly significant relationship was demonstrated between androstenedione and XbaI or PvuII polymorphisms, the highest levels of the hormone being found in the xx and pp genotypes (P<0.05 as compared to XX or PP, ANCOVA followed by least significant difference (LSD) multiple comparisons). This suggests that the ER genotype may determine the function of the sex-steroid system not only at the receptor level but also at the level of hormone synthesis. The pathogenetic role of this association in diseases related to menopause, such as osteoporosis, remains to be determined.

Aged↗
PubMed2002

Dehydroepiandrosterone status in postmenopausal women is determined by the gene for the vitamin D receptor.

Data documenting the indirect interaction of vitamin D and bone metabolism via hormonal systems are rare. The authors analysed the predictive role of the vitamin D receptor (VDR) gene for circulating sex steroids and their precursors in postmenopausal women. Using the PCR technique, the polymorphic FokI, ApaI, TaqI and BsmI sites of the VDR gene were determined in relation to serum dehydroepiandrosterone sulphate (DHEAS), androstenedione (AD), testosterone, and estradiol levels. After adjustment to body mass and years since menopause, circulating DHEAS was higher in the Ff genotype than in ff (p < 0.001) and FF genotypes (p < 0.05, ANCOVA followed by least significant difference multiple comparison tests). The Ff genotype also contributed to the highest BMD at the hip (p < 0.01 as compared to ff genotype) and at the spine (p < 0.05). No significant associations were found between ApaI, TaqI and BsmI polymorphisms and serum DHEAS or between FokI, ApaI, TaqI or BsmI and serum androstenedione, testosterone or estradiol. The study shows that the VDR gene predicts synthesis and/or metabolism of sexual steroid preursor DHEA in parallel with bone mineral density (BMD). The results indicate that DHEA production and bone mass share a common genetic control through VDR.

Aged↗
PubMed2002

Vitamin D receptor gene polymorphisms, bone mineral density and bone turnover: FokI genotype is related to postmenopausal bone mass.

The relationship between vitamin D receptor (VDR) intragenic polymorphisms FokI, BsmI, ApaI and TaqI and bone mineral density (BMD) or biochemical markers of bone remodeling were investigated in 114 Czech postmenopausal women, on the average 62.5+/-8.9 years of age. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in the VDR locus. Bone mineral density was measured at the lumbar spine and at the hip by dual-energy X-ray absorptiometry (DEXA, g/cm2). After adjusting for age and the body mass index (BMI), subjects with the ff genotype had 9.4% lower BMD at the hip than those with the Ff genotype (p=0.0459, Tukey's test). FF individuals had an intermediate BMD at the hip. A similar pattern of lower lumbar spine BMD was also found in ff individuals, but it did not reach statistical significance. There was no relationship between BsmI, ApaI and TaqI VDR polymorphisms and BMD at any skeletal site. Subjects with Aa (ApaI) genotypes had higher levels of propeptide of type I collagen (PICP) than homozygous AA (p=0.0459, Tukey's test). In FokI, BsmI and TaqI restriction sites the biochemical markers of bone remodeling did not differ by genotype. In addition, no significant difference was observed in VDR genotypic distribution between osteoporotic women and non-osteoporotic controls in the study group. To conclude, the FokI genotype of the vitamin D receptor gene is related to bone mass at the hip in Czech postmenopausal women, whereas the importance of remaining VDR genotypes was not evident.

Aged↗
PubMed2001

Systemic insulin-like growth factor-I, insulin and vitamin D status in relation to age-associated bone loss in women.

This cross-sectional study, performed on 146 healthy (n = 64) or osteoporotic but otherwise normal (n = 82) pre- (n = 38) or post-menopausal (n = 108) female subjects, analyzed the relationships between bone mineral density (BMD) (measured by dual-energy X-ray absorptiometry), parameters of bone remodelling, indices of calcium homeostasis and systemic IGF-I or insulin levels against a background of natural aging. BMD (g/cm(2)) at the hip correlated to serum IGF-I concentration (r = 0.207, p < 0.05), as well as to insulin levels (r = 0.241, p < 0.01), while BMD at the spine correlated only to IGF-I levels (r = 0.173, p < 0.05). After adjustment for age, body mass index, serum PTH, vitamin D status and calcitonin levels, neither IGF-I nor insulin levels could be significantly related to BMD at the spine or hip. On the other hand, 25-OH vitamin D(3) was found to be an important predictor of BMD at the hip (beta = 0.1686, p = 0.0437). In conclusion, this study failed to demonstrate a predictive importance of insulin-IGF-I axis to the development of bone mass. Instead, a significant predictive value to BMD at the hip was documented for serum 25-OH vitamin D(3).

Absorptiometry, Photon↗
PubMed2001

[Advantages of active vitamin D metabolites in the treatment of osteoporosis as compared with calciferol].

Vitamin D is one of the most important regulating agents in the development of bone mass. Therefore administration of calciferol along with calcium in patients with nutritional vitamin D deficiency leads to improvement of bone density. In patients with osteoporosis who do not respond to vitamin D, insensitivity of osseous tissue to the active metabolite of vitamin D--1,25(OH)2 D3--is involved or inadequate synthesis of active metabolites in the liver or kidneys. Administration of 1alpha-OH vitamin D3 and in particular 1,25(OH) 2D3 improves the general calcium balance in the organism and increases by direct osteoforming action the value of bone mass and improves its quality. Administration of active vitamin D metabolites is unequivocally better in treatment of involutional osteoporosis, either along with calcium or in combination with some antiresorption substance, in osteoporosis associated with chronic inflammatory diseases, after organ transplantation or glukcocorticoid treatment. Even patients with postmenopausal osteoporosis respond better to 1,25(OH)2D3.

25-Hydroxyvitamin D 2↗
PubMed2000

The pathophysiological implications of circulating androgens on bone mineral density in a normal female population.

In this cross-sectional study performed on 147 healthy or osteoporotic, but otherwise normal premenopausal (n = 26 and n = 13, respectively) or postmenopausal (n = 40 and n = 68, respectively) women aged 40.1+/-9.9 and 61.9+/-8.9 years, respectively (range 20-82 years), serum ovarian and adrenal sex steroids and their relationship to bone mineral density (BMD) were evaluated. The levels of dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (AD), and estradiol correlated positively with BMD at the hip and spine as did serum testosterone with BMD at the spine. An inverse relationship was found between sex hormone binding globulin (SHBG) levels and BMD at the spine and hip. After adjustment for age, body mass, and sex steroid confounders, the bioavailable testosterone value (but not the DHEAS, DHEA, AD, or SHBG) values was demonstrated to be an independent determinant of BMD at the spine (beta 0.18, P<0.02) and hip (beta 0.24, P<0.02). Similarly, estradiol was found to be an independent determinant of BMD at the spine (beta 0.25, P<0.007). However, only SHBG levels (but not other steroid parameters) correlated positively with indices of bone remodeling, namely, serum osteocalcin and cross-linked telopeptide of type I collagen (ICTP). The present study suggests that a major decline in index of free testosterone (testosterone/SHBG) may influence the development of female osteoporosis. The clinical significance of circulating SHBG levels in the assessement of bone metabolic turnover remains to be established.

Adult↗
PubMed2000

Lack of melatonin response to acute administration of nifedipine and diltiazem in healthy men.

Calcium antagonists have been shown to influence some endocrinological processes in mammals. The use of calcium channel blockers in clinical practice is well documented. The current study monitored nocturnal melatonin, prolactin, and cortisol levels in 19 healthy volunteers before and after administration of calcium channel blockers. The effect of nifedipine was tested in 9 subjects, while diltiazem was administered in 10 men. The nocturnal profile of the given parameters was studied between 23:00 and 05:00 h. At midnight (zero time), the participants were given placebo, nifedipine (in a sublingual dose of 20 mg) or diltiazem (in a single dose of 90 mg). The hypothesis that calcium channel blockers decrease nocturnal melatonin secretion has not been confirmed. The mean nocturnal levels of melatonin between 01:00 and 05:00 h were: 78.1+/-8.8 (control study) vs. 82.4+/-10.2 ng/l (nifedipine study) and 73.0+/-5.3 ng/l (control study) vs. 75.1+/-5.1 ng/l (diltiazem study). In conclusion, the calcium channel blockers used in this study do not alter the nocturnal melatonin secretory process in healthy men.

Adult↗
PubMed2000

[An unusual case of primary hyperparathyroidism in a woman with Gorlin-Goltz syndrome].

Nevoid basal cell carcinoma syndrome (NBCCS) has been known to coincide with different forms of other neoplasias; however, parathyroid adenoma in this syndrome has not previously been described. The authors report a case of such association in a 50-year old white woman. The adenoma was verified before operation by biochemical, isotopic and cytologic methods and later, after the excision of adenoma, histologically.

Adenoma↗
PubMed1999

Circulating beta(2) microglobulin in relation to bone metabolism: implications for bone loss with aging.

The aim of this cross-sectional study was to evaluate the relationships between circulating beta(2) microglobulin (beta(2) m) and bone mineral density (BMD), parameters of bone remodeling, vitamin D metabolites, parathyroid hormone (PTH), estradiol levels, and age in a group of 165 clinically healthy or osteoporotic, but otherwise normal untreated women. In this group of women, systemic beta(2) m correlated with BMD (g/cm(2)) levels for total hip and Ward's triangle (r = -0.298, P < 0.0001; and r = -0.299, P < 0.0001, respectively), but only at the borderline level with BMD at the spine (r = -0.145, P = 0.0604). Serum beta(2) microglobulin markedly correlated with age (r = 0.512, P = 0.0001). beta(2) m levels correlated with indices of bone remodeling, as well as with serum creatinine and estradiol levels. However, after stratification of all analyses by age, body mass index, and serum 25OHD(3), 1, 25(OH)(2)D(3), PTH, or estradiol levels (using standard multiple regression and stepwise forward regression models), only 25OHD(3) was found to be an independent predictor of BMD at the hip, including Ward's triangle, as estradiol of BMD at the spine. On the other hand, beta(2) m was not associated with BMD at any of the measured regions. Also, no association was found between serum PTH and BMD values. Therefore, systemic beta(2) m seems to be an indicator of bone remodeling in the course of natural skeletal aging rather than a variable independently predicting bone loss.

Absorptiometry, Photon↗
PubMed1997

[New drugs with positive effects on bones].

The paper concerns the nontraditional treatment of osteoporosis using endogenous substances regulating bone metabolism, and also new drugs. NO in high concentrations decreases the activity of osteoclasts, scavenges superoxides which destroy connective tissue, and activates 1 alpha-hydroxylase in kidneys. Bone metabolism is effectively influenced by donors of NO or by modulators of NO synthase. Osteoclastic function is also inhibited by vitamin K. The administration of the vitamin is indicated in osteoporotic patients with proven vitamin K deficiency. Antiestrogens (tamoxifen), ipriflavon and analogues of wortmannin have antiresorptive activity. Under certain conditions parathyroid hormone (PTH) is anabolic for bone. The positive effect on bone was confirmed with the subcutaneous administration of small doses of PTH simulating physiologic pulsatile secretion, as well as the intact somatotropin-IGF-I (insulin like growth factor-I) axis. PTH is extremely useful, especially in osteoporosis induced by hypoestrinism. Somatotropin (GH) also has an anabolic effect on bone. The hormone stimulates bone metabolism with a prevalence of formation due to direct action on bone, as well as by means of IGF-I. Further growth factors with positive osteoprotic effect are TGF-beta (transforming growth factor-beta), FGF (fibroblast growth factor) and calcium conserving dihomogammalinoleic acid. Magnesium influences bone in different ways. It activates osteoblasts, increases bone mineralization, and enhances the sensitivity of target tissues (incl. bone) to PTH and 1,25(OH)2 vitamin D3, Under certain conditions however, magnesium can stimulate bone resorption. A more potent factor than magnesium is stroncium, which not only activates osteoblats but decreases the number of osteoclasts, thus abolishing bone resorption and enhancing formation. Bicarbonates are also favourable for bone. NaHCO3 together with potassium citrate stimulates osteoblasts and enhances bone mineralisation. In the review other prospective substances are also discussed. The osteoprotic effects of most of these factors were confirmed in vitro and in studies in animals, but their use in clinical practice is still a matter for investigation. Mutual interactions with classical osteoprotic drugs remain to be established.

Animals↗
PubMed1997

Effect of 1,25(OH)2 vitamin D3 on circulating insulin-like growth factor-I and beta 2 microglobulin in patients with osteoporosis.

To test the hypothesis that growth factors mediate the stimulatory effect of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] on bone remodeling in osteoporosis, the authors studied the effect of the secosteroid administration in two doses (1 microgram/day and 2 micrograms/day) for 14 days on circulating insulin-like growth factor-I (IGF-I), beta 2 microglobulin, and osteocalcin in 18 osteoporotic women. The biological effectiveness of the treatment was controlled by a decline of serum intact parathyroid hormone. Compared with the values before treatment, 1,25(OH)2D3 increased means of plasma IGF-I, beta 2 microglobulin, and serum osteocalcin significantly; however, the effects were only apparent after the higher dose of the drug (169 +/- 26 versus 134 +/- 28 ng/ml, P < 0.01; 2.08 +/- 0.1 versus 1.92 +/- 0.1 micrograms/ml, P < 0.05; and 8.5 +/- 1.3 versus 5.4 +/- 1.1 ng/ml, P < 0.01, respectively). The authors conclude that exogenous 1,25(OH)2D3 promotes the production of IGF-I and beta 2 microglobulin in osteoporotic patients in parallel to the marker of osteoblastic function, osteocalcin, which supports the tested hypothesis.

Calcitriol↗