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Biomedical subjects

M Hammarström

Publications and source records attributed to M Hammarström.

At least 19 recordsLinked to original sources

Nitric oxide induces endometrial secretion at implantation time.

BACKGROUND: Uterine cervical secretory cells receive a sympathetic cholinergic secretomotor innervation. Glandular nitric oxide (NO) production has been proposed to be a prerequisite for muscarine-induced carbohydrate secretion from endometrial glands and cervical glands at ovulation time and from the seminal vesicle glands. Nitric oxide has also been suggested to have a significant role in the process of implantation and early pregnancy in the mouse, a process, which has also been compared with an inflammatory response. METHODS: The carbohydrate secretion from everted guinea pig uterine horns placed in organ baths was estimated. Polymerase chain reaction was performed in order to identify the isoforms of nitric oxide synthase (NOS). results. Carbamylcholine chloride (Carbachol) induced carbohydrate secretion of the endometrium, whereas L-NNA and L-NAME inhibited the Carbachol-induced secretion. The isomer D-NAME had no effect on Carbachol-induced secretion. The NO donor GTN induced carbohydrate secretion of the endometrium. The addition of the nitrergic inhibitor of soluble guanylyl cyclase (sGC) ODQ to Carbachol and to the NO donor GTN gave a reduced response. No synergism was seen when the sGC stimulator YC-1 was applied together with Carbachol. Three isoforms of NOS - endothelial NOS (eNOS), cytokine-inducible NOS (iNOS), and neuronal (nNOS) - were identified at implantation time and may take place in the endometrial cell. CONCLUSIONS: The results of this study suggest that glandular NO production is a prerequisite for the autonomic nervous modulation of endometrial secretion in the guinea pig and that NO may play a role in the implantation time.

Animals↗

Influence of physical activity on urinary leakage in primiparous women.

The impact of physical activity on urinary leakage (UL) has previously been considered, but not in relation to first pregnancy and delivery. The aim of this study was to describe physical activity and urinary leakage before, during and after the first childbirth. The subjects who were invited to participate in the study were taken consecutively from nine maternity clinics in the northwest part of Stockholm County, and the study group included 665 primiparous women. The mean age of the women was 28 (range 17-43) years. The women answered one questionnaire during the 36th gestation week and another 1 year post partum. Physical activity/exercises were classified according to their impact on the pelvic floor, and the women were divided into three groups: high-impact exercise (n=327), low-impact exercise (n=84) and the inactive group (n=254). The results showed a high intensity and frequency of physical activity in the participating primiparous women. Risk factors for UL were symptoms of a dysfunctional pelvic floor and connective tissue disorders and high-impact physical activity before pregnancy, while low-impact activity seemed to promote continence. If urinary leakage was present before pregnancy, it persisted in most women during pregnancy and 1 year post partum.

Adolescent↗

Prevalence of urinary leakage in nulliparous women with respect to physical activity and micturition habits.

In order to survey the influence of physical activity and micturition habits on urinary leakage (UL) in women before their first pregnancy, a study including 725 women attending nine maternity clinics in the northwest area of Stockholm was performed. During the 36th gestational week the women answered a questionnaire regarding the pre-pregnancy situation regarding UL, micturition habits and physical activity. Thirty-nine percent of the women, mean age of 28 (range 17-43) years, had experienced occasional UL. Of these, the majority (79%) had symptoms of stress urinary leakage and 21% had urge symptoms. Two percent were incontinent according to the definition of the International Continence Society (ICS). In a multivariate analysis age, inability to interrupt the urine flow and high-impact physical activity turned out to be independent risk factors for UL and thus should be observed together with traditional factors concerning UL in nulliparous women.

Adolescent↗

Clinical outcome or abdominal urethropexy-colposuspension: a long-term follow-up.

The aim of this study was to investigate the long-term results of abdominal urethropexy-colposuspension in terms of cure rate of stress urinary incontinence, complications and side effects. Between 1985 and 1992, 169 women between 27 and 79 years old underwent abdominal urethropexy-colposuspension at Stockholm Söder Hospital. In 1997 they were invited to participate in a long-term follow-up study, 5-11 years after the operation. One hundred and thirty-one women (78%) were willing to attend for a clinical review; 38 were lost to follow-up. At the follow-up visit all women were assessed with medical history, symptoms of incontinence, and their satisfaction and problems after the operation, following a predefined protocol. Peri- and postoperative data were retrieved from the files. The patients underwent a gynecological examination, measurement of residual urine volume and a provocative leakage test. One hundred and nine women (83%) were satisfied with the results of the operation and 22 (17%) were not. Seventy-one (54%) were subjectively completely dry, 48 (35%) had a little leakage and 14 (11%) had frequent leakage; 122 women were continent in the provocation test, and only 9 (7%) demonstrated leakage. The cure rate for stress incontinence was 93%. According to their medical histories 63 (48%) women had mixed incontinence before their operation. At the follow-up examination 43 of these 63 women still had symptoms of urgency. Twenty-six women with genuine stress incontinence before the operation had developed urgency or urge incontinence during the follow-up period. Urge symptoms before operation was a negative prognostic factor for a good outcome in terms of subjective cure of incontinence, but had no impact on objective cure rate or satisfaction of the operation. The cure rate for stress incontinence was high but still there were women who were not satisfied with the operation. Most of these complained of urge incontinence. There were few serious complications. The objective cure rate was better than the subjective cure rate.

Adult↗

Human gamma delta T cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules.

The functional properties, regarding parasite growth inhibition in vitro, the cytotoxic potential and cytokine profiles of human gammadelta+ and alphabeta+ T cells, T-cell lines and clones stimulated with Plasmodium falciparum-antigen-or T-cell mitogen in vitro were investigated. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and specific primers, mRNA for the cytolytic molecules perforin, granzyme A and B, Fas and Fas ligand (FasL) were detected in both the gammadelta- and the alphabetaT cells. Despite this fact, only gammadeltaT cells inhibited, both Vdelta1+ and Vdelta2+, the in vitro growth of the asexual blood stages in a dose dependent manner. The inhibition required cell-to-cell contact and was not observed until the second parasite replication implied that the likely gammadeltaT-cell target was the extracellular merozoite or schizont. The failure of alphabetaT cells to inhibit the growth of the parasite suggests requirement of additional cytolytic molecules/signals or different receptor specificities exhibited by the gammadeltaT cells. Both the gammadelta- and alphabetaT cells expressed mRNA for a large number of cytokines. Interferon (IFN)-gamma, interleukin (IL) IL-5, IL-6, IL-8, tumour necrosis factor alpha (TNFalpha), tumour necrosis factor beta (TNF-beta)/lymphotoxin (LT) and T-cell growth factor beta-1 (TGF-beta1) were observed in all activated clones tested. No IL-3 was detected, while IL-1beta, IL-2, IL-4, IL-10 and GM-CSF were variably expressed. In conclusion, our data show that gammadeltaT cells in malaria nonimmune individuals inhibit the asexual blood stages of P. falciparum malaria, while similarly activated alphabetaT cells do not. Thus, it is likely that the gammadeltaT cells could play a mandatory role in the elimination of parasites and/or the regulation of the early immune response to malaria infection.

Animals↗

Autonomic nervous influence of the female guinea-pig urinary bladder during the oestrus cycle.

The mammalian urinary bladder receives dual innervation. The excitatory innervation is considered to be partly cholinergic and partly mediated via NANC-receptors. Several (co-)transmitters have been suggested. The adrenergic inhibitory innervation is mediated via alpha- and beta-receptors. Female sex hormones could change autonomic influence of urogenital organs. It was considered to be of interest to characterize the spontaneous and nerve stimulation-induced muscular activity in the urinary bladder of the female guinea-pig during the oestrus cycle. Both the spontaneous activity and nerve-induced activity varied according to the hormonal status of the animal. An alpha-adrenergic inhibitory influence was identified. It was further confirmed that the excitatory innervation could not be blocked by the cholinergic antagonist scopolamine, while alpha-beta-methylene ATP partly inhibited nerve stimulation-induced smooth muscle response, most prominent at cycle day 6. Indomethacin did not impair spontaneous activity or nerve stimulation-induced activity. Nitric oxide reduced nerve stimulation-induced responses on cycle day 12. Imperative urinary bladder contractions are reported to diminish after oestrogen use and in the female a hormonal effect of the nervous influence on the urinary bladder smooth muscle is suggested.

Adenosine Triphosphate↗

Is glandular formation of nitric oxide a prerequisite for muscarinic secretion of fructose in the guinea-pig seminal vesicle?

The significance of nitric oxide (NO) formation in seminal secretion was studied in guinea-pig seminal vesicles. The nitric oxide synthase (NOS) activity was estimated and reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry was performed. Furthermore, cyclic guanosine 3,5-monophosphate (cGMP) concentration as well as fructose secretion from isolated vesicles was estimated. High Ca2+-dependent NOS activity as well as prominent glandular NADPH-diaphorase staining was found in the secretory epithelium. The NOS inhibitors N(G)-nitro L-arginine methyl ester (L-NAME) and N(G)-nitro L-arginine (L-NNA) inhibited carbachol-induced fructose secretion but the D-isomer to L-NAME had no effect. When L-arginine was administered together with L-NAME, no inhibitory effect on the carbachol-induced fructose secretion could be seen. Nerve-induced fructose secretion was also inhibited by L-NAME. The NO donor glyceryl trinitrate (GTN) increased the fructose secretion. Carbachol or GTN did not increase cGMP levels, nor was fructose secretion inhibited by a guanylate cyclase inhibitor (ODQ). Our results suggests that glandular NO production is a prerequisite for muscarinic fructose secretion in the seminal vesicle via a cGMP-independent pathway.

Animals↗

Premature rupture of the membranes (PROM) at term in nulliparous women with a ripe cervix. A randomized trial of 12 or 24 hours of expectant management.

OBJECTIVE: To compare maternal and neonatal outcomes after 12 or 24 hours of expectant management in healthy nulliparous women with a ripe cervix and PROM at term. DESIGN: A prospective, randomized study. LOCATION: Karolinska Hospital, Stockholm, Sweden. SUBJECTS: Two hundred and five healthy nulliparous women with singleton pregnancies, cephalic presentation, gestational duration 36 to 42 weeks, randomized to 12 or 24 hours of expectant management after evaluation of the cervical score (> 5). If spontaneous labor did not occur, induction was performed with oxytocin after 12 or 24 hours, respectively. MAIN PARAMETERS: Maternal early morbidity and neonatal infections, obstetric intervention rate (cesarean section or instrumental delivery). RESULTS: The cesarean section rate was 4% in each group. The vacuum extraction rate was 21% in each group. Induction of labor was performed in 47% of the women allocated to 12 hours of expectant management vs 17% of the women allocated to 24 hours of expectant management (p < 0.05). The maternal morbidity rate was almost negligible. Only a few fetal infections occurred and no difference was noted between the groups. CONCLUSIONS: In healthy nulliparous women at term with a ripe cervix, expectant management over 24 hours vs 12 hours resulted in fewer inductions of labor and no increase in instrumental deliveries, without any increase in neonatal or maternal morbidity.

Adult↗

Sympathetic regulation of fructose secretion in the seminal vesicle of the guinea-pig.

Fructose secretion of everted guinea-pig seminal vesicles was studied in vitro. Carbachol produced dose dependent increase in fructose secretion. The effect was blocked by scopolamine but not by hexamethonium, mecamylamine, tetrodotoxin or previous denervation. High concentrations of acetylcholine also increased fructose secretion. This response was not augmented by physostigmine. Methoxamine reduced secretion. Methoxamine, terbutaline, clonidine and vasoactive intestinal peptide counteracted carbachol. Field stimulation produced increased secretion that was not blocked by autonomic drugs, tetrodotoxin or previous denervation. Stimulation of the hypogastric nerve produced frequency dependent increase in fructose secretion. The effect was blocked by tetrodotoxin and scopolamine but not enhanced by physostigmine. If the hypogastric nerve was stimulated close to the seminal vesicle the response was unaffected by hexamethonium but proximal stimulation was blocked. After chronic proximal denervation of the hypogastric nerve, stimulation close to the seminal vesicle produced enhanced response. Destruction of the peripheral ganglia at the base of the seminal vesicle abolished the response. Sections showed that most secretory nerves enter the organ at its base. Phentolamine or yohimbine but not prazosine or propranolol or guanethidine enhanced the secretory response to distal hypogastric nerve stimulation. Tyramine counteracted the response but after reserpinization it was enhanced by tyramine. It is concluded that the secretory cells of the guinea-pig seminal vesicle have a sympathetic secretomotor innervation by short cholinergic neurones with a preganglionic supply via the hypogastric nerve. Inhibitory alpha 1 and beta 2-adrenoreceptors are present on the cells but neurogenic adrenergic inhibition of the secretion is essentially prejunctional and due to activation of inhibitory alpha 2-receptors on the secretomotor nerves.

Adrenergic Agonists↗

Autonomic nervous modulation and effects of a prostaglandin synthase inhibitor on human cervical secretion.

Modulation of cervical secretion at ovulation time was studied in 10 women with regular menstruations. In an in-vivo model with repeated collection of mucus samples during three 90-min periods, the amounts of mucus in a control cycle and in three experimental cycles were compared. Drugs interacting with the autonomic nervous system and a prostaglandin synthase inhibitor were administered at time of ovulation. The cholinomimetic drug carbacholine significantly increased cervical secretion, while the anticholinergic drug butylscopolamine markedly inhibited this secretion. A long-lasting decrease in secretion was seen after administration of the prostaglandin synthase inhibitor diclofenac. Beside regulation of cervical secretion by the ovarian hormones, these results suggest an autonomic nervous modulation of cervical secretion, and in addition an impact on cervical by a prostaglandin synthase inhibitor. The effects on fertility regulation in the female are discussed.

Adult↗

Influence of prostaglandins and a prostaglandin H synthase inhibitor on cervical secretion of the guinea-pig.

The modulatory effects of several prostaglandins and a prostaglandin H synthase inhibitor (indomethacin) on basal as well as nerve stimulation induced secretion from the cervical glands of the guinea-pig were studied. Hypogastric nerve stimulation resulted in a secretory response of +113%. Indomethacin dose dependently inhibited this secretory response. Prostaglandins E2, F2 alpha and I2 inhibited and 19-OH prostaglandin E1 reduced nerve stimulation induced secretion. Prostaglandin I2 and 19-OH PGE1 markedly enhanced basal secretion, while indomethacin as well as PGE2 and PGF2 alpha did not induce any secretion of cervical glands. However, PGF2 alpha in combination with the alpha-adrenergic blocker phentolamine resulted in an increase in secretion. The inhibitory effect of prostaglandins on cholinergic secretory innervation might be due to stimulation of adrenergic nerves exerting an inhibitory influence on cholinergic secretomotor innervation. It is suggested that PGI2 and 19-OH PGE1 exert postjunctional stimulatory effects on the secretory lining and that a lack of secretory effect of PGF2 alpha at least in part may be due to stimulatory effects on adrenergic neurons, inhibiting cholinergic secretomotor transmission. Thus, in this in vitro study it is shown that metabolites of the arachidonic acid cascade and a prostaglandin H synthase inhibitor can modulate cervical secretion and thus maybe influence fertilization.

Animals↗

Adenosine modulation of neuroeffector transmission in guinea-pig uterine smooth muscle.

Effects of adenosine and adenosine analogues on neuroeffector transmission in separate layers of the guinea-pig uterine smooth muscle during different phases of the oestrus cycle were studied. Adenosine (ADO), N6-[(R)-1-methyl-2-phenylethyl]- adenosine (R-PIA) and 5'-N-ethylcarboxamideadenosine (NECA) enhanced spontaneous contractile activity as well as contractile responses to nerve stimulation or direct muscle stimulation in the longitudinal and circular muscle layers both at the time of ovulation and implantation. The agonist potency order was R-PIA greater than or equal to NECA greater than ADO. Furthermore, in the circular muscle layer inhibitory effects were seen at time of implantation and the agonist potency for this inhibitory effect was NECA greater than R-PIA greater than or equal to ADO. 8-p-sulphophenyltheophylline (8-PSOT) antagonized both the stimulatory and inhibitory effects of the purines and 8-p-sulphophenyltheophylline applied to untreated preparations inhibited nerve-induced contractile activity. NECA inhibited stimulation-induced release of 3H in preparations incubated with [3H]noradrenaline. We suggest that adenosine and its analogues can modulate adrenergic neuroeffector transmission in guinea-pig uterine smooth muscle via action at postjunctional receptors stimulating contractile activity and prejunctional receptors inhibiting transmitter release. In the circular muscle layer postjunctional receptors inhibiting contractile activity were evident at time of implantation. Furthermore, endogenous purines exerting a stimulatory action on the neuroeffector transmission were likely formed during the present experimental conditions.

Adenosine↗

Yeuhchukene--an indole derivative interacting with guinea pig reproduction.

Natural yuehchukene in doses of 10 mg/kg/day induced a 40% reduction of pregnancies in the guinea pig as compared with controls (p less than 0.05). Yuehchukene also caused a reduction in litter size which, however, was not significant indicating limited toxicity of the drug. An inhibition of ovum fertilization and/or implantation is suggested as the mechanism of action.

Animals↗

Effects of adenosine analogues on guinea-pig endometrial secretion.

The effect of adenosine analogues on guinea-pig endometrial secretion was studied in vitro at defined days of the estrous cycle. The adenosine analogues, 5'-N-ethylcarboxamideadenosine (NECA) and (N6-[(R)-1-methyl-2-phenylethyl]-adenosine (R-PIA), induced endometrial secretion at ovulation time (cycle days 16-1) and at implantation time (cycle days 6-7). The secretory response to NECA was antagonized by 8-p-sulfophenyltheophylline. Scopolamine had no effect on secretion induced by the adenosine analogues. Endometrial secretion induced by field stimulation was inhibited by NECA but not by R-PIA at ovulation time. At implantation time, both NECA and R-PIA reversed the response to field stimulation to values below the basal resting level. The latter effect was antagonized by phentolamine. These findings suggest that adenosine analogues can induce guinea-pig endometrial secretion by action at stimulatory adenosine receptors, and concomitantly inhibit secretomotor neurotransmission.

Adenosine↗

First trimester live pregnancy and subsequent fetal loss. Impact of transcervical CVS and colonization of the cervix.

A consecutive series of 224 women undergoing transcervical chorionic villi sampling (CVS) were analyzed for the presence of cervical microbes. The outcome of pregnancy was related to age, number of aspirations and to the presence or not of microbes. The CVS group was compared to a group of 200 women with live fetuses at 8-11 weeks of gestation not undergoing CVS (ultrasound, US group). In the US group the miscarriage rate was 8.5% with 5.9% occurring after the 16th week of gestation. In the CVS group 20.3% ended as a miscarriage, 28.9% of these after the 16th week. There was no correlation between miscarriage rate and maternal age in the US group. In the CVS group younger women had a prominent rate of fetal loss. In the present study the risk of fetal loss after CVS was associated with a previous history of spontaneous abortions, with several aspirations performed, and with bacterial colonization of the cervix--candida and gardnerella excluded.

Abortion, Spontaneous↗

Effects of a new indole derivative on guinea pig reproduction.

The effect of a new indole derivative, (1,1,3-trimethyl-3-(3'-indolyl)-1,2,3,4-tetra-hydrocyclopent[b]-in dole) denoted 1 related to indomethacin and yeuhchukene 2 were tested on guinea pig reproduction. In mating experiments ten females were given compound 1 p.o. from cycle day 14 and onwards throughout pregnancy. Two groups of ten females each were used as controls. Conception occurred significantly (p less than 0.001) faster in the treatment group. The litter size was significantly (p less than 0.001) smaller after treatment with the indole derivative. Dams and pups did not seem to have been adversely affected by the treatment as judged by their exterior, behavior and survival. The results are suggested to be due to a reduction in the number of ova available for conception (litter size) in combination with improved conditions for ovum implantation and/or a facilitated sperm migration in the female genital tract. These effects are discussed in relation to known effects of arachidonic acid metabolites on reproduction.

Animals↗