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Biomedical subjects

L Viinikka

Publications and source records attributed to L Viinikka.

At least 19 recordsLinked to original sources
PubMed1992

Cyclosporin reduces renal prostanoid excretion in type 1 diabetic patients.

Prostacyclin and thromboxane A2 are important regulators of kidney blood flow. To examine whether changes in their metabolism could be involved in the nephrotoxicity of cyclosporin, we determined urinary excretion of 6-keto PGF1a and dinor-6-keto PGF1a (prostacyclin metabolites) and dinor-TxB2 (thromboxane metabolite) in five newly diagnosed type 1 diabetic patients during and after stopping cyclosporin therapy. In the resting state, cyclosporin had no effect on prostanoid excretion. In response to exercise, urinary excretion of 6-keto PGF1a was reduced by 50% (P less than 0.02), dinor-6-keto PGF1a by 15% (P less than 0.05) and dinor-TxB2 by 45% (P less than 0.02), while albumin excretion increased 4.5-fold (P less than 0.05) during cyclosporin therapy. Simultaneously, there was a rise in serum creatinine concentration, and renal biopsy specimens obtained from three patients showed periglomerular and interstitial fibrosis and tubular atrophy. After the discontinuation of cyclosporin therapy, serum creatinine concentrations returned to normal, histological changes improved and there was an associated rise in urinary prostanoid excretion. These data suggest that a reduction in renal prostanoid synthesis by cyclosporin may diminish renal blood flow and function, and lead to histological changes in the kidney.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Urinary excretion of prostacyclin and thromboxane metabolites in threatened preterm labor: effect of indomethacin and nylidrin.

OBJECTIVE: We studied the role of smooth muscle-relaxing prostacyclin and its endogenous antagonist, thromboxane A2, in preterm labor by assessing the urinary output of the breakdown products of prostacyclin (6-keto-prostaglandin F1 alpha and 2,3-dinor-6-keto-prostaglandin F1 alpha) and those of thromboxane A2 (thromboxane B2, 2,3-dinor-thromboxane B2). STUDY DESIGN: Thirty-three women in preterm labor between 25 and 34 weeks of gestation were studied before, during, and after treatment with indomethacin (n = 16) or nylidrin (n = 17). Urinary prostanoid levels were determined by high-performance liquid chromatography followed by radioimmunoassay, and the excretion was expressed as nanograms of prostanoids per millimole of creatinine. Statistical analyses were done by paired and unpaired Student t test, by Spearman's correlation, and by Wilcoxon signed-rank test. RESULTS: Preterm labor was accompanied by a median 32% higher output of prostacyclin and thromboxane A2 metabolites as compared with those in 25 controls. At 8 hours after the start of treatment indomethacin induced maximal drops in 6-keto-prostaglandin F1 alpha (70%), in dinor-6-keto-prostaglandin F1 alpha (60%), in thromboxane B2 (85%), and in dinor-thromboxane B2 (95%) excretion. Within 1 week after the cessation of indomethacin, output of prostacyclin metabolites had recovered to pretreatment values, whereas output of thromboxane A2 metabolites was yet lower than the pretreatment value. Nylidrin induced no change in the output of prostacyclin and thromboxane A2 metabolites. CONCLUSION: Threatened preterm labor is associated with a rise in prostacyclin and thromboxane A2 synthesis. Indomethacin inhibits more thromboxane A2 than does prostacyclin synthesis. These findings may explain the fetal vascular changes during maternal indomethacin treatment.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Modulation of prostacyclin production by cytokines in vascular endothelial cells.

The data presented in this review clearly show that many different cytokines regulate the synthesis of PGI2 in vascular EC (Tables 1 & 2). Since these agents are synthesized, stored, and/or released from platelets, leukocytes and cells present in the vascular wall (Fig.), they are to be found at sites of vascular injury and may, through their effect on the synthesis of PGI2 and other prostanoids, regulate thrombogenesis and atherogenesis. Despite the mass of detailed data, the picture is still fragmentary. Very little, for instance, is known about the 'orchestral effects' of different combinations of cytokines. In addition, it seems that the regulation of PGI2 synthesis by cytokines varies with the species and with the type of vasculature from which the cells originated. However, discrepancies may also be due to the use of different culture conditions. Moreover, we must remember that the present data are almost exclusively from in vitro studies, and the representativeness of these results in in vivo situations remains to be clarified.

Animals↗
PubMed1992

Nonpregnant women with a history of habitual abortion have normal and luteal function independent production of prostacyclin and thromboxane A2.

OBJECTIVE: To see if changes in prostacyclin and thromboxane A2 (TXA2) production during early pregnancy in women with habitual abortion is a pregnancy-induced change, we compared the production of these prostanoids in habitual aborters and in healthy controls in nonpregnant state and related it to luteal function. DESIGN: Comparison between patients (n = 16) with a history of at least three consecutive miscarriages and healthy controls without a history of abortions (n = 11). SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Habitual aborters and control women exhibited no change in the urinary output of the stable degradation products of prostacyclin and TXA2 when studied between 0 and 2 and 5 and 8 days after the luteinizing hormone peak. Habitual aborters as a whole, or when subgrouped to those with normal (10 cycles) or defective luteal function (12 cycles) did not differ from the control series with regard to prostacyclin and TXA2 production. CONCLUSIONS: Productions of prostacyclin and TXA2 are not relative to the luteal function and are normal in nonpregnant women with a history of habitual abortion.

Abortion, Habitual↗
PubMed1992

The role of prostaglandins in obstetrical disorders.

All pregnancy-associated tissues are capable of producing prostaglandins including PGI2 and TXA2. In normal pregnancy there is a dominance of PGI2 over TXA2 which may contribute to the maternal circulatory adaptation to pregnancy. Furthermore, both fetoplacental PGI2 and TXA2 production are important regulators of the fetal blood supply. It has been clearly established that in pre-eclampsia PGI2 production decreases in the fetoplacental tissues and quite probably also in the maternal tissues. The effect of this change may be further exaggerated by the simultaneous stimulation in pre-eclampsia of TXA2 production. The reason for PGI2 deficiency is not known. Other vasoactive agents, such as endothelin, may act in concert with prostaglandins. Relative PGI2 deficiency is likely to exist also in IUGR and lupus anticoagulant syndrome of pregnancy. In the latter, lupus anticoagulant may directly inhibit the synthesis of PGI2. One study suggests PGI2 deficiency also in early pregnancies of women with a history of repeated abortions. Prostaglandin production increases during full-term labour, and similar but smaller changes also occur in preterm labour. A silent bacterial infection may trigger the onset of preterm labour through cytokine-stimulated increase of prostaglandin production. No data were found on prostaglandin production in post-term pregnancies. That oligo-polyhydramnios is possibly prostaglandin mediated is suggested by the control of polyhydramnios by indomethacin treatment. Smoking decreases the production of PGI2 and possibly increases that of TXA2, which may lead to decreased blood flow and IUGR. Which constituent of cigarette smoke exerts this effect is not known. Ethanol consumption causes aberrations in prostaglandin metabolism which cannot be directly connected with fetal alcohol effects.

Abortion, Habitual↗
PubMed1991

Thromboxane dominance and prostacyclin deficiency in habitual abortion.

To evaluate the significance of vasoactive prostanoids in habitual abortion, we measured urinary excretion of prostacyclin metabolites (6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and of thromboxane A2 metabolites (TxB2 and 2,3-dinor-TxB2) during 25 pregnancies in 22 women with recurrent spontaneous abortion (RSA). The control group were 16 pregnant women with no history of abortion. Ultrasound examination at first follow-up appointment showed a living fetus in 23 pregnancies of women with RSA. 9 of these pregnancies ended in abortion; 14 continued to term as did all the pregnancies in the control group. Compared with controls, women with RSA had a lower (p less than 0.05) ratio of prostacyclin to thromboxane between weeks 4 and 7 of gestation and a lower (p less than 0.01) output of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11. Women whose pregnancies ended in abortion had higher (p less than 0.05) output of 2,3-dinor-TxB2 between weeks 4 and 7 of gestation and lower (p less than 0.01) excretion of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11 compared with women whose pregnancies proceeded to term. We conclude that deficiency of vasodilatory prostacyclin may be a factor in habitual abortion.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Epidermal growth factor in human tear fluid: a minireview.

This minireview deals with the presence of epidermal growth factor (EGF) in human tear fluid. It explains the occurrence of EGF in tear fluid, the origin of EGF and its dependency on tear fluid dynamics. The alterations in tear fluid EGF concentrations that occur during diseases of the ocular surface are described and discussed in the context of the current knowledge about the interaction between EGF and EGF receptors. The possible clinical implications of topical treatment with EGF are considered.

Epidermal Growth Factor↗
PubMed1991

Human serum stimulates endothelin-1 synthesis more potently than prostacyclin production by cultured vascular endothelial cells.

Human serum stimulated the synthesis of a vasoconstrictive peptide, endothelin-1 (ET-1), and a vasodilatory prostanoid, prostacyclin (PGI2), by cultured human umbilical vein endothelial cells in a concentration- and time-dependent manner. Incubation in 20% concentration of the serum for 24 h stimulated ET-1 synthesis almost six-fold while PGI2 production increased two-fold. In addition, a tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), inhibited the serum-induced ET-1 production and stimulated PGI2 synthesis in a concentration- and time-dependent manner. Our results suggest that human serum derived factor(s) stimulate the production of vasoconstrictive ET-1 more potently than the synthesis of vasodilatory PGI2 by human vascular endothelial cells and that the production of these agents is differentially regulated by PMA.

Blood↗
PubMed1991

Cytoskeleton-dependent release of human platelet epidermal growth factor.

To study the source of immunoreactive epidermal growth factor (ir-EGF) released by thrombin formation we removed 99.9% of the leukocytes normally present in platelet-rich plasma and induced coagulation with 30 mM of Ca2+. The absence of leukocytes did not reduce the amount of ir-EGF released; thus platelets are most likely the only source of the ir-EGF released during aggregation. To identify the site of ir-EGF in platelets we exposed washed platelets to collagen or thrombin and compared the kinetics of releases of ir-EGF, beta-thromboglobulin (bTG, an alfa-granule marker), ATP (dense granule marker), N-acetyl-beta-D-glucosaminidase (NAGA, a lysosome marker) and lactate dehydrogenase (LDH, a cytoplasmic marker). Release of ir-EGF started immediately and continued linearly. The process differed clearly from the releases of the granule markers, which occurred readily, and were completed in a few minutes. The release of ir-EGF also differed from the leakage of LDH, the start of which was delayed greater than 5 min, but then proceeded linearly. Cytochalasin B inhibited the release of hEGF, but demecolcine had no effect. We conclude that the ir-EGF released from platelets during aggregation derives neither from the granules nor the cytoplasma. The assembly of cytoskeleton is needed for its release.

Blood Platelets↗
PubMed1991

Human milk stimulates prostacyclin production by cultured human vascular endothelial cells.

Prostacyclin (PGI2) is an antithrombotic and vasodilatory factor, which is produced mainly by the vascular endothelium. Little is known about how this process is regulated. We investigated the effect of human milk on PGI2 synthesis by human vascular endothelial cells by measuring its stable metabolite, 6-keto-prostaglandin F1 alpha, by RIA. Human milk induced dose- and time-dependent stimulation of PGI2 production, whereas cow's milk was ineffective. The lowest concentration of human milk that stimulated the production of PGI2 was 0.1%, and 10% induced a 2.4- to 3.4-fold increase. The effect of human milk was detectable after 2 h and was blocked by inhibitors of transcription, translation, and cyclooxygenase. Boiling abolished the activity, but acetone extraction enhanced it. A 10% concentration of acetone-extracted human milk stimulated the release of endothelial cell PGI2 by 6.6-fold. In human milk samples we found no correlation between the amount of immunoreactive epidermal growth factor (EGF) and the activity stimulating PGI2 synthesis. Furthermore, EGF antibodies did not inhibit the activity. This is the first demonstration that human milk stimulates PGI2 production by endothelial cells. We conclude that human milk is a potent inducer of PGI2 production by human vascular endothelial cells and that the stimulatory activity is not due to EGF.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Ocular disease leads to decreased concentrations of epidermal growth factor in the tear fluid.

The concentration of epidermal growth factor (EGF) in tear fluid (TF) was recently shown to decrease with increasing tear fluid flow (TFF). The purpose of the present study was to clarify the effects of ocular surface disease on the TF EGF concentrations. Tear fluid samples (n = 243) were collected from diseased eyes by means of blunted glass capillaries. The time of collection was measured for each sample, and the tear fluid flow in the capillaries (TFFc) was calculated. The concentration of human EGF (hEGF) was determined using a time-resolved immunofluorometric assay (TR-IFMA). For statistical analysis diagnosis-dependent multigrouping was performed and the data of the patient groups were compared to the data for a control group. The control material consisted of 271 TF samples collected from healthy eyes before (n = 59) and after stimulation of reflex tearing (n = 212). It was shown that TF specimens of patients (n = 243) contained significantly (p less than 0.001) less EGF (mean 952 pg/ml) than the TF of healthy control individuals before (n = 59 samples; mean 6589 pg/ml) or after stimulation of reflex tearing (n = 212 samples; mean 2762 pg/ml). The EGF concentration of every patient group was significantly lower than that found in the TF of control individuals both before and during reflex tearing (p less than 0.001). The rate of EGF released with TF during collection did not differ significantly between the various groups of patients or from that released with the TF of normal individuals before induction of reflex tearing.(ABSTRACT TRUNCATED AT 250 WORDS)

Corneal Diseases↗
PubMed1990

Estrogen-androgen antagonism in the regulation of epidermal growth factor in mouse submandibular salivary gland and kidneys.

To eludicate hormonal regulation of epidermal growth factor (EGF) concentration we studied the effects in adult female mice of ovariectomy and postovariectomy treatments with testosterone plus estradiol on the EGF concentrations in submandibular salivary gland (SMG), plasma, kidneys and urine. In the tissues, we also studied the location of EGF immunohistochemically and measured EGF mRNA. After ovariectomy, SMG EGF first decreased to one third of preovariectomy level. After postovariectomy day 10 it started to increase and reached by day 80 3.5-fold the preovariectomy level. Simultaneously, EGF mRNA increased. Testosterone treatment further strongly augmented the levels of both EGF mRNA and EGF. A small dose of estradiol counteracted slightly the mRNA effect of testosterone. After ovariectomy plasma EGF first increased 1.3-fold by day 10, then returned to the initial levels, and rose again 1.6-fold by day 80. Testosterone treatment induced a further 1.5-fold increase. Estradiol did not counteract this effect. Kidney EGF decreased 15% by postovariectomy day 20. This was preceded by a decrease in EGF mRNA from day 10 onwards. The EGF concentration recovered during the 80 days, but the EGF mRNA level stayed low. Testosterone treatment further reduced the levels of both EGF mRNA and EGF. This effect was counteracted by estradiol. Urine EGF increased after ovariectomy to a peak (1.7-fold) by day 40. It then returned to the preovariectomy levels by day 80. Testosterone treatment increased urinary EGF 1.9-fold; concomitant estradiol had no effect.

Androgen Antagonists↗
PubMed1990

Urinary excretion of prostacyclin and thromboxane metabolites in climacteric women: effect of estrogen-progestin replacement therapy.

To study the role of vasodilatory prostacyclin and vasoconstrictory thromboxane A2 in climacteric vascular instabilities, overnight urine samples were collected from sixteen women suffering from hot flushes and sweating before, during and after the six months' cyclic estradiol-desogestrel therapy as well as from ten non-climacteric control women. The urine was assayed for 6-keto-PGF1a and 2,3-dinor-6-keto-PGF1a (metabolites of prostacyclin) as well as for thromboxane B2 and 2,3-dinor-thromboxane B2 (metabolites of thromboxane A2) by means of HPLC and radioimmunoassay. No difference was seen in baseline prostaroid output between the climacteric and non-climacteric study groups. Furthermore, no relation was observed between individual prostanoid excretion and severity of vasomotor symptoms before replacement therapy. The replacement therapy abolished or markedly alleviated hot flushes and sweating, but prostanoid output did not change. Our data imply that climacteric symptoms are not accompanied by changes in the production of prostacyclin and thromboxane A2.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Comparison between squamous cell carcinoma-associated antigen and CA-125 in patients with carcinoma of the cervix.

Serum levels of CA-125 and squamous cell carcinoma-associated antigen (SCC) were measured in 30 patients with squamous cell carcinoma and 12 patients with adenocarcinoma of the uterine cervix. SCC was elevated in 67% of patients with squamous cell carcinoma but in only 25% of patients with adenocarcinoma. In contrast, CA-125 was elevated in 75% of patients with adenocarcinoma but in only 26% of patients with squamous cell carcinoma. These data demonstrate the applicability of the measurement of CA-125 as a tumor marker for cervical adenocarcinoma and confirm the value of the measurement of SCC antigen in patients with cervical squamous cell carcinoma. Moreover, we show that measurement of SCC antigen in adenocarcinoma and measurement of CA-125 in squamous cell carcinoma are of insufficient clinical value.

Adenocarcinoma↗
PubMed1990

Epidermal growth factor in mice: effects of estradiol, testosterone and dexamethasone.

To clarify the influence of steroids on the metabolism of epidermal growth factor, we studied the effects on its concentrations in adult male and female mice of 1. gonadectomy, 2. postgonadectomy treatments with estradiol and testosterone, and 3. treatment with dexamethasone. We also measured its mRNA levels in submandibular salivary glands and kidneys after ovariectomy. After gonadectomy, the male mice had 1.4-fold higher mean epidermal growth factor concentration in the urine than the female, in contrast to a 1.5-fold reverse difference in intact mice; the female mice had 2.5-fold higher concentration in the submandibular glands than the male animals, in contrast to a 4.5-fold reverse difference in intact mice. The kidney sex difference of intact mice (male greater than female) was abolished. In both gonadectomized sexes, treatment with testosterone increased the concentration of epidermal growth factor in plasma and the submandibular gland; treatment with estradiol increased the concentration in urine and decreased it in the submandibular gland. Treatment with dexamethasone decreased the concentration of epidermal growth factor in plasma of the male mice, and in urine of the female mice, thus decreasing the sex differences. In the submandibular gland and the kidneys, dexamethasone increased the concentration. The mRNA levels were higher in the submandibular gland and lower in the kidneys in the ovariectomized than in the intact female mice. The effects of sex steroids on epidermal growth factor concentrations are mediated through modulation of its gene activity. Testosterone has an increasing and estradiol a decreasing effect in the submandibular gland. Estradiol has also an increasing effect in the kidneys.

Animals↗
PubMed1990

Epidermal growth factor in mice: changes during circadian and female reproductive cycles.

To clarify the variation of mouse epidermal growth factor production during the 24-h and female reproductive cycles, we measured its concentrations in the plasma, submandibular salivary gland, urine, kidneys and liver of adult male and female mice during consecutive 12-h dark and 12-h light periods, different stages of pregnancy, and lactation. The concentration of epidermal growth factor in the submandibular gland showed no circadian changes. In plasma and in the liver it increased during the dark period, whereas in urine and in the kidneys it peaked in the daytime. In the submandibular gland the concentration decreased during early pregnancy, but it returned to the non-pregnant levels by mid-pregnancy. In plasma it decreased progressively during pregnancy and recovered during lactation. In urine and the kidneys the concentration of epidermal growth factor increased after early pregnancy; with a further great increase in the kidneys during lactation. In the liver the concentration was clearly below the non-pregnant levels during late pregnancy and lactation.

Animals↗
PubMed1990

Acetylsalicylic acid and the balance between prostacyclin and thromboxane A2.

Arachidonic acid is metabolized in endothelial cells to antiaggregatory, vasodilatory prostacyclin (PGI2), and in platelets to aggregatory, vasoconstrictory thromboxane A2 (TxA2). The balance of these two prostanoids is supposed to be involved with thrombogenesis and atherogenesis. Acetylsalicylic acid (ASA) inhibits irreversibly the key enzyme of the synthesis of these prostanoids, i.e. cyclo-oxygenase. Platelets do not synthetize new protein, but endothelial cells do. Because of this, and certain pharmacokinetic characteristics of ASA, it should be possible to shift the balance between PGI2 and TxA2 to the dominance of the former with the proper dose of this drug. Altogether more than 50,000 subjects have volunteered for studies on the effect of ASA in the primary or secondary prevention of myocardial infarction or ischemic stroke. The results show that it is possible to reduce vascular attacks by ASA. Furthermore, ASA has also found to prevent pre-eclampsia. Conclusions on the effect of ASA on the PGI2/TxA2-balance are hampered by uncertainties concerning the measurement PGI2 and TxA2 productions in vivo. It is, however, evident that the doses of ASA used in most trials have been high enough to inhibit partly also the production of PGI2. Whether smaller doses or less frequent administration would be more efficient, remains to be studied.

Arteriosclerosis↗