Role of PACAP in the female reproductive organs.
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Adolescent↗
Biomedical subjects
P Alm
Publications and source records attributed to P Alm.
PACAP occurs in sensory nerve fibers and participates in ocular inflammation in the rabbit.
PACAP is a sensory neuropeptide; it occurs together with CGRP in a population of C fibers in the rabbit eye. PACAP is likely to be involved in the inflammatory response in as much as PACAP-induced responses mimic the symptoms of inflammation and because the concentration of PACAP-LI in the aqueous humor increased greatly in response to noxious stimuli. The observation that capsaicin releases both PACAP and CGRP from the iris and ciliary body supports the view that PACAP is present in C fibers in the rabbit eye.
Animals↗
Inducible nitric oxide synthase increases in regenerating rat ganglia.
Nitric oxide synthase (NOS) exists in several isoforms. In this study we used immunocytochemistry to investigate one isoform, inducible NOS (iNOS), in the nodose ganglia (NG) and in the superior cervical ganglia (SCG) of the rat. iNOS was present in many neurones of the NG, while no iNOS-positive cells could be observed in the SCG. At 24 and 48 h following a crush lesion to the vagus nerve, expression of iNOS-immunoreactivity had increased in the NG. iNOS-immunoreactivity increased in both the NG and SCG of ganglia cultured for 24 and 48 h. The results show that an increase in iNOS-immunoreactivity accompanies regenerative processes in two peripheral ganglia, suggesting that nitric oxide, the product of iNOS activity, could be involved in nerve regeneration.
Animals↗
Regulation of neuronal nitric oxide synthase mRNA levels in rat brain by seizure activity.
The regulation of neuronal nitric oxide synthase (NOS) mRNA levels during kindling epileptogenesis in the rat brain was investigated using in situ hybridization. Following 40 rapidly recurring seizures evoked by hippocampal stimulations, NOS mRNA expression decreased by 56% in the dentate granule cell layer (maximum at 2 h) and increased by 420,105 and 1260% in the CA1 and CA3 pyramidal layers and piriform cortex, respectively (maximum at 12-24 h). Gene expression had returned to control levels after one week. The presumed alterations of nitric oxide production, following the changes in NOS mRNA shown here, may modulate synaptic function during kindling development, and could influence neuronal vulnerability after epileptic insults.
Analysis of Variance↗
Pituitary adenylate cyclase activating polypeptide (PACAP): occurrence and vasodilatory effect in the human uteroplacental unit.
UNLABELLED: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide which was originally isolated from ovine hypothalamus. PACAP exists in at least two biologically active forms, PACAP-38 and PACAP-27. The aim of this study was to establish the distribution, localization and smooth muscle effects of PACAP-38 and PACAP-27 in the human uteroplacental unit. For this purpose we used radioimmunoassay, immunocytochemistry and in vitro studies of the effect of the peptides on smooth muscle activity. RESULTS: By radioimmunoassay both peptides were detected throughout the uteroplacental unit. The concentrations of PACAP-27 were in general low, ranging from 1/6-1/25 of the corresponding PACAP-38 concentrations. PACAP-immunoreactivity was localized in nerve fibres of the lower segment of the pregnant uterus, but the number of PACAP-immunoreactive nerves was very clearly reduced compared to the corresponding isthmic region of non-pregnant myometrial tissue. PACAP-immunoreactive fibres were not observed in placenta or in the umbilical cord. Both PACAP-38 and PACAP-27 caused a concentration-dependent relaxation on stem villous arteries and on the intramyometrial arteries. Neither of the peptides displayed any effect on non-vascular smooth muscle specimens from the term pregnant myometrium. In conclusion the findings suggest a vasoregulator role of PACAP in the human uteroplacental unit.
Adult↗
Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors.
The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.
Adolescent↗
Nitric oxide synthase-containing nerves and ganglia in the dog prostate: a comparison with other transmitters.
The distribution of nitric oxide synthase immunoreactive nerves in the dog prostate was compared to the total innervation (as estimated by protein gene product 9.5 immunoreactivity), and to that of adrenergic (tyrosine hydroxylase-immunoreactive), cholinergic (acetylcholinesterase-positive), and some peptidergic nerves immunoreactive towards vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and helospectin. Clusters of ganglia with cell bodies containing acetylcholinesterase, or one of these six immunoreactive components, were found in the dorsal capsule. Coarse nerve trunks expressing these immunoreactive components extended from the ganglia, and divided into varicose terminals in the capsule and intraglandular smooth muscle strands, and gave off further branches, which surrounded acini and accompanied ducts. The labelling for nitric oxide synthase generally coincided with that for vasoactive intestinal peptide within cell bodies and nerves of various types. Cell bodies, nerve trunks and varicose terminals showing labelling for pituitary adenylate cyclase-activating peptide and helospectin were generally also labelled for vasoactive intestinal peptide. The innervation pattern suggests that nitric oxide may act in concert with vasoactive intestinal peptide and related peptides in the control of prostatic smooth muscle activity and secretion.
Acetylcholinesterase↗
Cytogenetic findings in four malignant mixed mesodermal tumors of the ovary.
Short-term cultures of four malignant mixed mesodermal tumors of the ovary were cytogenetically analyzed. The primary tumor was examined in three cases, whereas in one case the sample was obtained from a residual tumor mass after chemotherapy. The tumor sampled after cytostatic treatment had a relatively simple karyotype with numerical changes that included pentasomy 12 and an i(1)(q10) as the only structural abnormality. Karyotypic analysis of the three primary tumors revealed extensive structural as well as numerical aberrations, i.e., a picture similar to that seen in the few malignant mixed mesodermal tumors with karyotypic anomalies described previously. Rearrangements of chromosome 1, leading to loss of distal 1p, and homogeneously staining regions have so far been the most frequent cytogenetic changes in this tumor type. Malignant mixed mesodermal tumors of the ovary thus seem to be karyotypically identical to the more numerous mixed mesodermal tumors of uterine origin, and they do not differ substantially in this respect from pure ovarian carcinomas.
Chromosome Aberrations↗
Involvement of nitric oxide in acute spinal cord injury: an immunocytochemical study using light and electron microscopy in the rat.
The possibility that nitric oxide participates in the pathophysiology of spinal cord injury was examined using a constitutive isoform of neuronal nitric oxide synthase immunoreactivity in a rat model. Spinal cord trauma was produced by making an incision into the right dorsal horn of the T10-11 segments. Five h after trauma, a marked upregulation of NOS-immunostained neurons was seen in the perifocal T9 and T12 segments of the cord. The immunolabelling was most pronounced in the dorsal horn of the ipsilateral side. Topical application of an antiserum to nitric oxide synthase (NOS) 2 min after injury prevented the trauma-induced upregulation of NOS-immunoreactivity. In contrast, application of preabsorbed serum or L-NAME, an inhibitor to NOS, was ineffective in reducing the induction of NOS-immunoreactivity. Trauma caused a marked expansion of the cord and resulted in marked cell changes. This expansion and cell reaction was significantly reduced following application of NOS antiserum but it was not seen after application of preabsorbed antiserum or L-NAME. Our results for the first time show that a focal trauma to the spinal cord has the capacity to upregulate neuronal NOS immunoreactivity and that application of NOS antiserum has a neuro protective effect. This indicates that nitric oxide is somehow involved in the pathogenesis of secondary injuries after spinal cord trauma.
Amino Acid Sequence↗
Long-term renal morphology and function following enterocystoplasty (refluxing or anti-reflux anastomosis): an experimental study.
OBJECTIVE: To study the morphology and function of the upper urinary tract over the long-term in dogs with an enterocystoplasty and a refluxing or anti-refluxing uretero-intestinal anastomosis. MATERIALS AND METHODS: Subtotal cystectomy and "cup" ileocystoplasty were performed in 13 dogs. The right ureter was implanted into the cystoplasty with a refluxing technique in seven and with an anti-reflux procedure in six dogs. The left renal unit acted as an intact control in 11 dogs, while in two the intramural part of the left ureter was incised to produce reflux. Thus, of the 26 renal units, nine had a refluxing junction (anastomosis), six were anti-refluxing and 11 served as intact controls. Total and separate glomerular filtration rates (GFRs) were measured preoperatively and regularly thereafter, and cystometry, urography and ascending enterocystography were performed. At necropsy, urine was obtained for culture from the cystoplasty and renal pelves, and both kidneys were examined histologically. RESULTS: The cystometric pressure was low in 12 of the 13 dogs: urography showed no obstruction. The fall in separate GFR did not differ significantly among the groups (with and without reflux protection, and control units). Reflux was detected in three of nine renal units with refluxing anastomosis and in three of 11 control units. Bacteriuria was found in the cystoplasty in all dogs; the incidence in the upper urinary tract was seven of eight renal units with a refluxing anastomosis, one in five of those with an anti-refluxing anastomosis and three of nine control units. Pyelonephritis was found in none of the control kidneys, in six of nine kidneys with a refluxing and in two of six with an anti-refluxing anastomosis: it was less severe in the latter. CONCLUSION: Refluxing ureteric implantation in a low-pressure enterocystoplasty was commonly associated with bacteriuria in the upper urinary tract and with pyelonephritis. Thus, anti-reflux implantation was beneficial for renal preservation in this setting.
Animals↗
Localization and activity of haem oxygenase and functional effects of carbon monoxide in the feline lower oesophageal sphincter.
1. In the feline lower oesophageal sphincter (LOS), the distribution of the carbon monoxide (CO) producing enzymes haem oxygenase (HO)-1 and -2 was studied by immunohistochemistry and confocal microscopy, the HO activity was measured and the possible role for CO as a mediator of relaxation was investigated. 2. HO-2 immunoreactivity was abundant in nerve cell bodies of the submucosal and myenteric plexus. Approximately 50% of the HO-2-containing myenteric cell bodies were also nitric oxide synthase- and vasoactive intestinal peptide (VIP)-immunoreactive. In addition, HO-2 immunoreactivity was seen in nerve fibres, in non-neuronal cells dispersed in the smooth muscle and in arterial endothelium. HO-1 immunoreactivity was confined to non-neuronal cells in the smooth muscle, similar to those positive for HO-2. 3. Activity of HO, measured as CO production, was observed in LOS homogenates at a rate of 1.00 +/- 0.05 nmol mg-1 protein h-1. This production was inhibited by the HO inhibitor, zinc protoporphyrin-IX (ZnPP). 4. In isolated circular smooth muscle strips of LOS, developing spontaneous tone, exogenously administered CO evoked a concentration-dependent relaxation reaching a maximum of 93 +/- 3%. This relaxation was accompanied by an increase in cyclic GMP, but not cyclic AMP levels. The relaxant response was attenuated by methylene blue, but unaffected by tetrodotoxin. Repeated exposure to CO resulted in a progressive reduction of the relaxant response. 5. ZnPP caused a rightward-shift of the concentration-response curves for the relaxant responses to VIP, peptide histidine isoleucine, and pituitary adenylate cyclase activating peptide 27. 6. ZnPP and tin protoporphyrin-IX (another inhibitor of HO) did not affect nonadrenergic, noncholinergic relaxations induced by electrical field stimulation. Nor did ZnPP affect relaxations induced by 3-morpholino-sydnonimine or forskolin. 7. The present findings, showing localization of HO immunoreactivity to both neuronal and nonneuronal cells of the feline LOS, ability of LOS to produce CO and a relaxant effect of CO in circular LOS muscle, suggest a role for CO as a peripheral messenger.
Animals↗
The contribution of nitric oxide to endotoxin-induced ocular inflammation: interaction with sensory nerve fibres.
1. The actions of nitric oxide (NO) have been investigated in an endotoxin-evoked ocular inflammatory model in the rabbit, with particular emphasis on the relationship between NO, sensory nerves (C-fibres) and the C-fibre neuropeptides, calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP). 2. Endotoxin, injected intravitreally, evoked inflammatory responses, i.e. conjunctival hyperaemia, miosis and protein extravasation, reflected by the aqueous flare response (AFR). In control rabbits, the maximum AFR was 66.5 +/- 9.5 (arbitrary units). Pretreatment with the NO synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NAME, 200 mg kg-1) given by intravenous injection, inhibited the endotoxin-evoked responses; the AFR was 16.5 +/- 1.9 (n = 8, P < 0.001) and the conjunctival hyperaemia was abolished. 3. Endotoxin-evoked ocular inflammation is associated with the release of CGRP and PACAP from C-fibres. In the eyes challenged with endotoxin, the concentrations of PACAP-27, -38 and CGRP in the aqueous humour were 58.2 +/- 10.9, 54.4 +/- 12.4 and 5526 +/- 519 (pmoll'), respectively. L-NAME inhibited the release of PACAP-27, -38 and CGRP; the concentrations were 14.3 +/- 2.5, 13.5 +/- 2.5 and 510 +/- 67 (pmoll-1), respectively (n = 8, P < 0.01 or 0.001). 4. Intravitreal injection of 0.3 nmol CGRP induced conjunctival hyperaemia and AFR; the maximum AFR was 140.2 +/- 11.4. L-NAME suppressed the response induced by CGRP; the AFR was 23.4 +/- 5.5 (n = 8, P < 0.001). L-NAME abolished the conjunctival hyperaemia induced by PACAP-27 and -38 (0.3 nmol) and reduced the AFR. 5. The inflammatory cells that infiltrated the uvea, cornea and aqueous humour in large numbers in response to intravitreal injection of endotoxin were found to express inducible NOS. L-NAME prevented the appearance of such cells. 6. Our findings suggest that NO plays an important role in the endotoxin-evoked ocular inflammation in the rabbit: NO activates C-fibres causing release of C-fibre neuropeptides into the aqueous humour. In addition, NO mediates scme of the ocular effects of CGRP and PACAP, since L-NAME suppressed the AFR induced by these peptides.
Animals↗
Selective microsurgical sympathetic denervation of the rat pancreas.
Autonomic nerves have been implicated in the regulation of endocrine and exocrine pancreatic secretion. The purpose of the present study was, therefore, to develop a simple, reproducible technique for selective sympathetic denervation of the rat pancreas. Under ether anesthesia a midline laparotomy was performed, the pancreas and spleen were freed from adhesions. The peritoneum was incised over the superior and inferior pancreaticoduodenal arteries and the splenic artery at their origin. The incised areas were stained with 1% toluidine blue solution. The pancreaticoduodenal and splenic nerves were visualized and resected. 1, 2 and 3 weeks after the denervation procedure the norepinephrine (NE) content of the pancreatic tissue was determined. Cholinergic and nitric oxide synthetase (NOS)-immunoreactive nerve structures were identified by immunohistochemistry 1 week after denervation. In denervated tissue the NE content after 1 week was 98% lower than measured in controls. With time, there was a gradual increase of the NE content, although it reached only 25% of the values measured in sham-operated animals at 3 weeks. There was no concomitant denervation of the duodenum. Cholinergic and NOS nerve structures were still present 1 week after denervation.
Animals↗
Methodological aspects of flow cytometry DNA analysis in endometrial carcinoma, with special reference to sampling and reproducibility.
Two adjacent paraffin-embedded sections manifested concordance in ploidy status in 96% of cases (45/47), and the standard deviation (SD) for SPF was 2.7%. Analysis of 'micro-heterogeneity', within a distance of < or = 700 microm, yielded results for concordant ploidy status in 94% of cases, and the SD for SPF was 1.9% (n = 17). Frozen and paraffin-embedded material yielded concordant results for ploidy status in 87% (39/45) of cases, and SPF values were significantly lower (mean difference 1.5%) in the frozen samples. Diagnostic and repeat curettage material yielded concordant results for DNA ploidy status in 85% (40/47) of cases, and no significant difference in mean SPF (12% vs. 11%) was found. Discordant DNA ploidy results were attributable to small differences in the DNA histograms influencing the interpretation of near-diploid, near-tetraploid and small non-diploid cell populations, and the influence of debris on SPF estimation. On the basis of our findings and the practical advantage we recommend paraffin-embedded material from diagnostic curettage for FCM DNA analysis; the results are available sooner and the handling and transportation of tumor samples is more convenient.
Cryopreservation↗
Nitric oxide inhibits contraction of isolated pig ureteral smooth muscle.
PURPOSE: To investigate the L-arginine/nitric oxide (NO) pathway in the pig isolated ureter. MATERIALS AND METHODS: Functional inhibitory effects mediated by NO were assessed and correlated with cyclic nucleotide levels. Nitric oxide synthase (NOS) activity was measured by monitoring the conversion of [3H]-arginine to [3H]-citrulline. Immunohistochemical studies were performed. RESULTS: The NO-donor SIN-1 reduced in a concentration-dependent manner the frequency of contractions, whereas NO completely interrupted the contractile activity. In precontracted strips exposed to SIN-1 or NO, there were 6- and 12-fold increases of the cyclic GMP levels in comparison with control preparations. Activity of NOS was moderate. Overall innervation of the ureter was sparse, and there were few NOS-immunoreactive nerves. CONCLUSION: Although few NOS-containing nerves were found, pathways regulating the cyclic GMP levels of pig ureteral smooth muscle were demonstrated. Such pathways may be important targets for drugs producing relaxation of the mammalian ureter.
Animals↗
C1 inhibitor deficiency in a patient with rheumatoid arthritis--increased risk of adverse effects of penicillamine?
We report the coincidence of hereditary angioedema and rheumatoid arthritis in a male patient and in his father. During treatment with D-penicillamine the patient developed a transient lupus-like disorder with glomerulonephritis that resolved when D-penicillamine was discontinued. He later was diagnosed with malignant lymphoma. Impaired classical complement pathway function could have contributed to development of the drug reaction.
Angioedema↗
[Injuries caused by motorized lawn mowers--hand injuries the most common ones].
The powerful forces involved in the function of motorized lawnmowers can cause serious injuries. The study reported was based on a series of 81 cases of injury, that were treated at University Hospital, Umeå. Direct trauma to hand and foot was the most common injury mechanism, though high energy expulsion of objects from the machine was not uncommon. A common cause of direct trauma to hand or foot was attempting to clear grass or other matter from the vicinity of the rotating blades. Hand injuries were most common and occurred predominantly in men, whereas women and children accounted for a greater proportion of missile injuries instead. 25 per cent of all hand and foot injuries were amputating fractures. The preventive measures that could and should be implemented to reduce the risk of these injuries include improved shielding of rotating and heated parts, prevention of missile ejection, and the introduction of dead-man grip. The use of protective gear, and greater care in the use of motor mowers generally, would also reduce the risk of injury.
Accidents, Home↗
Nitric oxide synthase-immunoreactive, adrenergic, cholinergic, and peptidergic nerves of the female rat urinary tract: a comparative study.
The distribution and frequency of NO synthase (NOS)-immunoreactive (IR) nerves in relation to the general autonomic innervation, adrenergic, cholinergic and some peptidergic nerves, were investigated in the female rat urinary tract. NOS nerves were very frequent in the smooth musculature of the urethra together with cholinergic, adrenergic and neuropeptide Y (NPY)-IR nerves, whereas vasoactive intestinal peptide (VIP)-IR and calcitonin-gene-related peptide (CGRP)-IR nerves were much less abundant. NOS-IR, CGRP-IR and cholinergic nerves were also frequent in the longitudinal smooth musculature of the distal ureters and the ureteral orifices into the bladder, where no adrenergic, NPY-IR and VIP-IR nerves were found. In contrast, in the detrusor NOS-IR nerves were scarce. Bilateral pelvic ganglionectomy very pronouncedly decreased the number of any of the populations of nerves studied, whereas bilateral pelvic decentralization selectively reduced the number of CGRP-IR nerves in all structures and locations. Outflow obstruction very overtly reduced the number of NOS-IR nerves in parallel with the general autonomic innervation. Thus, in the rat female urinary tract, NOS-containing nerves particularly occur in regions with sphincteric functions such as urethra and ureteric orifices. In these regions NO may exert a transmitter role, both directly or by interaction with other transmitters/modulators.
Adrenergic Fibers↗