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L Viinikka

Publications and source records attributed to L Viinikka.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1990

Evidence of similar increases in bone turnover during nafarelin and danazol use in women with endometriosis.

Medical 'oophorectomy' by GnRH agonist or danazol is an effective treatment for endometriosis. Since increased bone loss is a potential risk of hypoestrogenism, we compared the effect of nafarelin and danazol treatment on bone metabolism. Twelve patients with laparoscopically confirmed endometriosis received nafarelin (400 micrograms day intranasally) and six patients danazol (600 mg day orally) for 6 months. Both treatments had already led to hypoestrogenism (E2 less than 21.6 pg/ml) after 3 months. They both were accompanied by an approximately 50% rise in 24-h urinary hydroxyproline output, suggesting accelerated bone resorption at 6 months; yet urinary calcium output did not change significantly. Serum osteocalcin rose by 80-120% and bone alkaline phosphatase activity by 34-40%, suggesting stimulated bone formation at the same time. No detectable changes ensued in cortical bone mineral content in the distal radius or in serum levels of calcium, calcitonin, parathyroid hormone, or aminoterminal propeptide of type III collagen. Three months after treatment, hydroxyproline output, serum osteocalcin and bone alkaline phosphatase were still elevated in women taking nafarelin, whereas only serum osteocalcin was elevated in women taking danazol. Our data thus suggest that bone turnover was increased during nafarelin and danazol therapy and that this effect was reversible.

Alkaline Phosphatase↗
PubMed1989

Neurological outcome after out-of-hospital cardiac arrest. Prediction by cerebrospinal fluid enzyme analysis.

The prognostic value of cerebrospinal fluid (CSF) and serum neuron-specific enolase and brain-type creatine kinase isozyme (CK-BB) measurements was studied in 75 consecutive victims of out-of-hospital cardiac arrest. All patients with a CSF neuron-specific enolase level of more than 24 ng/mL 24 hours after cardiac arrest remained unconscious and died. The CSF CK-BB level was as reliable as an index of brain injury. Cerebrospinal fluid neuron-specific enolase, CSF CK-BB and serum neuron-specific enolase levels correlated with the neurological outcome at 3 months. Thus, the analysis of these enzymes in CSF seems to be useful in the early prognostic assessment of cardiac arrest victims.

Adult↗
PubMed1989

Epidermal growth factor is a constant component of normal human tear fluid.

Epidermal growth factor (EGF) is a mitogenic polypeptide, which was first isolated from mouse submaxillary gland. Since EGF also stimulates the growth of corneal epithelial cells and only preliminary data exist on its presence in tear fluid, we studied the occurrence of human EGF (hEGF) in the tear fluid of 36 healthy persons (31 women and 5 men from 20 to 59 years of age; 60 eyes). hEGF, as measured by an immunofluorometric assay, was present in all tear fluid samples investigated. Its concentration varied from 200 to 2860 pg/ml (median, 705 pg/ml). The tear fluid hEGF concentrations differed less between the eyes of one individual than between individuals. The total amount of hEGF released to the tear fluid increased with fluid flow, but the higher the flow was, the lower the concentration of hEGF. We could not find any evidence of sex dependency in the hEGF concentrations. In demonstrating that hEGF is a normal component of human tear fluid, the results of this study suggest that hEGF may be important for conjunctival and corneal epithelial integrity.

Adult↗
PubMed1989

Mouse epidermal growth factor concentrations are altered by gonadectomy and treatments with estradiol and progesterone.

In adult male and female mice we compared the epidermal growth factor (EGF) concentrations after gonadectomy and studied the effects of postgonadectomy treatments with estradiol and progesterone. In gonadectomized mice the mean concentration of EGF in the submandibular salivary gland (SMG) was (7-fold) higher in the females than the males. In the kidneys the males had (1.3-fold) higher levels of EGF than the females. Yet, gonadectomized males had higher plasma EGF levels and females higher urinary EGF concentrations. Estradiol treatment clearly decreased the EGF concentration in the SMG and increased it in urine and kidneys. Progesterone decreased male kidney EGF. Combined treatment with estradiol and progesterone increased the EGF concentration in the male urine and SMG, and decreased it in male kidneys.

Animals↗
PubMed1989

Urinary excretion of prostacyclin and thromboxane degradation products in patients with ovarian malignancy: effect of cytostatic treatment.

We studied the effect of ovarian cancer and its chemotherapy on the urinary excretion of prostacyclin (PGI2) and thromboxane A2 (TxA2) hydration and metabolic products. In six patients we measured 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha (PGI2 products) and thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (TxA2 products) by HPLC followed by radioimmunoassay before, during and after the combined infusion of cisplatin, 4'epi-adriamycin and cyclophosphamide. Before the first cytostatic infusion, the urinary excretion of prostanoids was on average 4.4-5.8 times higher than in patients with ovarian endometriosis (n = 19). The infusion of cytostatics led to a 50-120% rise in the excretion of prostanoids during the first post-infusion 9 hours, but in the subsequent 10 hours their output was 25-45% below the initial value and remained low for at least 2 weeks. Following repetitive courses of cytostatics (2-4 per patient), prostanoid excretion tended to normalise. These data suggest that ovarian cancer is associated with increased production of PGI2 and TxA2, and that cytostatics suppress this production. This may be of biological significance in tumour behaviour and in the effect of cytostatics.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effects of estradiol and progesterone on epidermal growth factor concentration in plasma, bile, urine, submandibular gland and kidney of the mouse.

Testosterone is known to increase epidermal growth factor (EGF) concentrations in mouse plasma and submandibular salivary gland. We tested in adult sialoadenectomized (sx) and sham-operated female and male mice our hypothesis that female sex steroids also affect EGF concentrations in fluids and tissues. In 10-day treatment estradiol-17 beta increased the EGF concentration in male urine and in (sx) female plasma. Progesterone increased the concentration in both sexes in plasma (sx mice) and in the kidneys. In contrast, progesterone decreased it in female urine.

Animals↗
PubMed1989

Urinary excretion of prostacyclin metabolites in infants born after maternal preeclampsia or with birth asphyxia.

Decreased fetoplacental prostacyclin (PGI2) production has been shown in preeclampsia, and increased pulmonary PGI2 synthesis has been demonstrated in experimental hypoxia. We measured the urinary excretion of the main metabolites of PGI2, 6-keto-prostaglandin F1 alpha (6-keto) and 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3-dinor), during the first day of life in infants born to mothers with preeclampsia (n = 26), in infants with birth asphyxia (n = 12), and in control infants (n = 14). The mean excretion of 6-keto in control infants increased from 9.3 to 14.3 ng/h/1.73 m2 from 0-12 to 12-24 h of age, and a corresponding change from 3.5 to 7.0 ng/h/1.73 m2 was seen in 2,3-dinor excretion. In infants of preeclamptic mothers the excretion values at 0-12 and 12-24 h and the pattern of change were not significantly different from controls. In asphyxiated infants, the mean excretion values at 0-12 and 12-24 h of 6-keto (11.0 and 11.6 ng/h/1.73 m2) and 2,3-dinor (6.0 and 5.8 ng/h/1.73 m2) were not significantly different from control infants, but no increase was seen. We conclude that PGI2 production in infants of preeclamptic mothers is not impaired, but after perinatal asphyxia there is an altered pattern of PGI2 metabolite excretion, suggesting decreased production capacity.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Characterization of material with epidermal growth factor immunoreactivity in human serum and platelets.

We investigated the molecular nature of the epidermal growth factor immunoreactivity (ir-EGF) in serum and platelets of normal subjects. In serum, ir-EGF appeared and increased during spontaneous blood coagulation, reaching a plateau in 2 h. The mean plateau measured by time-resolved immunofluorometric assay was 778 pg/mL [130 pmol/L; range, 465-1352 pg/mL (78-225 pmol/L)] for men (n = 66), and 774 pg/mL (129 pmoL/L; range, 521-1114 pg/mL (87-186 pmol/L)] for women (n = 33). Serum samples (n = 9), when examined under nonreducing conditions by high performance liquid chromatography, contained three mol wt components. Their approximate proportions averaged 56 +/- 6% (+/- SD) for a 140K component, 22 +/- 9% for a 67K component, and 22 +/- 6% for a component coeluting with the 6K EGF standard. The molecular size distribution of ir-EGF released from isolated platelets varied with the treatment of the platelets. After stimulation with a Ca2+ ionophore, the proportions of the 140K, 67K, and 6K components were 61 +/- 11%, 20 +/- 8%, and 17 +/- 4% (n = 5), respectively, as in serum. In addition, we found a small amount, (approximately 1%) of a 17K component. When platelets (n = 6) were ruptured by sonication and repeated freeze-thawing, the 67K component formed 53 +/- 7% of the total; the proportions of the 140K, 17K, and 6K components were 14 +/- 7%, 2.1 +/- 0.7%, and 31 +/- 4%, respectively. Under reducing conditions the 17K and 6K components remained intact, but part of the 140K component and all of the 67K component were cleaved to a 35-37K form. After protease digestion of the higher mol wt components, the ir-EGF was exclusively of the 6K form. The 67K and 6K components bound to the EGF receptor, whereas the 140K component bound inconsistently. We conclude that treatment of platelets with Ca2+ ionophore produces ir-EGF components similar to those found in incubated serum but different from those obtained by freeze-thawing. The 67K mol wt component appears to be the main storage form of EGF in platelets; at least two independent mechanisms appear to exist for EGF release.

Blood Coagulation↗