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D Delbro

Publications and source records attributed to D Delbro.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacological preconditioning of rat liver by up-regulation of heme oxygenase 1.

PURPOSE: We investigated whether pharmacologically induced up-regulation of heme oxygenase 1 by pyrrolidine dithiocarbamate (PDTC) conferred protection against subsequent ischemia-reperfusion injury (IRI) to the rat liver after temporary vascular occlusion of 70% of the organ. METHODS: Female Wistar rats (200 to 250 g body weight) anesthetized with pentobarbitone were cannulated in the carotid artery and jugular vein. After laparotomy, a rubber band was applied around the entire vascular supply to the median and left lateral lobes, enabling vascular occlusion of 70% of the liver. A laser Doppler miniprobe was placed on the left lateral lobe to monitor peripheral liver blood flow (PLBF). Immediately upon completion of the surgery, the rats were administered either PDTC (50 mg/kg intravenously; n = 8) or its solvent (isotonic NaCl; n = 8). After 60 minutes, regional ischemia was induced for 30 minutes. The animals were then monitored for 2 hours of reperfusion. Blood samples for alanine transferase (ALT) estimation (as a measure of parenchymal injury) were drawn immediately prior to ischemia and reperfusion, as well as 60 and 120 minutes after reperfusion; PLBF was calculated at these times. RESULTS: ALT increased in the course of the experiments but there was no difference between the groups. The reduction in PBLF due to ischemia-reperfusion was significantly lower in the PDTC group: about 16% versus 40%, after 2 hours of reperfusion. CONCLUSION: Pretreatment with PDTC attenuated the disturbance of hepatic microcirculation, but not parenchymal injury, in the early phase of IRI.

Alanine Transaminase↗
PubMed2000

Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids.

The potential interaction between cyclooxygenase (Cox) and NO metabolic pathways in the control of local tumor growth was evaluated. Mice bearing either a sarcoma-derived tumor (C57B1; MCG 101) or a malignant melanoma (C3H/HeN; K1735-M2) were used. These models were principally different because they demonstrate, in tumor hosts, conditions with and without cancer cachexia, seemingly related to high and low production of prostanoids, respectively. Cox inhibitors (Cox-1 and Cox-2) decreased tumor growth by 35-40% in MCG 101-bearing mice but had no such effect on melanoma-bearing mice, despite the expression of the Cox-2 protein in melanoma cells. Indomethacin reduced prostanoid production in both tumor (MCG 101) and host tissues and reduced tumor cell proliferation, mainly in vivo. Nitric oxide synthase (NOS) inhibitors (N(omega)-nitro-L-arginine methyl ester and N(omega)-nitro-L-arginine) reduced tumor growth in vivo by approximately 50% in both tumor models. Tumor growth reduction, related to NOS inhibition, was unrelated to prostanoid production and was an in vivo phenomenon in both tumor models. Specific inhibitors of inducible NOS activity, unexpectedly, had no effect in any tumor model, although inducible NOS protein was present in tumor tissues in large amounts. A combination of Cox and NOS inhibitors had no additive effect on tumor growth (MCG 101). Cox inhibition increased tumor tissue (MCG 101) expression of cNOS mRNA but had no significant effect on tumor tissue expression of the transferrin receptor, vascular endothelial growth factor, or basic fibroblast growth factor. NOS inhibition increased tumor tissue content of cNOS mRNA but showed as well a trend to increase mRNA content of the transferrin receptor and vascular endothelial growth factor. Our results suggest that NOS inhibitors can decrease the local growth of tumors that are either responsive or unresponsive to Cox inhibition. This effect may reflect cross-talk between Cox and NOS pathways within or among tumor cells, or it may represent unrelated effects on tumor and host cells. Whether NO inhibition may be used therapeutically in clinical tumors that are unresponsive to eicosanoid intervention remains to be evaluated.

Animals↗
PubMed2000

The liver protective effect of ischemic preconditioning may be mediated by adenosine.

We investigated the involvement of adenosine in ischemic preconditioning (IPC) by the unspecific antagonist, 8-phenyltheophylline (8-PT). Anesthetized Wistar rats were treated as follows: 1. non-ischemic controls, 2. ischemic controls: 60 min of clamping of the common hepatic artery followed by 60 min reperfusion, 3. IPC: 10 min ischemia followed by 15 min reperfusion, prior to the identical ischemia-reperfusion (IR) period as in group 2, 4. 8-PT + IPC: 8-PT 10 mg/kg i.v. was given 10 min prior to the identical procedure as in group 3. The peripheral liver blood flow was monitored by laser-Doppler flowmetry. Blood alanine aminotransferase (ALT) was analyzed once every 60 min. IPC significantly reduced impairment of liver blood flow, as well as ALT increase during reperfusion. This effect was abolished by pretreatment with 8-PT. Adenosine appears to be a crucial effector in IPC. Clinical studies need to be undertaken to explore a possible effect of IPC in liver transplantation.

Adenosine↗
PubMed1998

Nitric oxide mediated inhibition of contractile activity in the human uterine cervix.

Nitric oxide (NO) is an important modulator of contractile activity in various tissues. The aim of the present study was to investigate the possible existence of an NO system within the human uterine cervix and to study the effects of NO on the cervix in early pregnancy. Cervical tissue specimens were obtained from 24 women in connection with first trimester legal abortion. NADPH diaphorase staining was used to identify nitric oxide synthase activity within the cervical tissue. Cylindrical tissue specimens were mounted in organ bath chambers for isometric registration of contractile activity. The presence of a functional NO system in the cervix was investigated by adding either sodium nitroprusside or spermine NONOate, two different NO donors, or 8-bromo cGMP, an analogue of the second messenger cyclic guanosine monophosphate (cGMP), to the organ baths. Positive NADPH diaphorase staining was clearly observed in the walls of blood vessels, in cervical smooth muscle cells, and cells scattered in the connective tissue. The NO donating drugs sodium nitroprusside and spermine NONOate both caused a dose-dependent inhibition of spontaneous contractile activity with significant inhibition at concentrations of 10(-5) and 10(-7) M respectively. Furthermore, the participation of NO in the regulation of cervical contractility was indicated by a significant concentration-dependent inhibition of spontaneous contractions when 8-bromo cGMP (10(-5)-10(-3) M) was added to the organ baths. The study indicates the existence of an NO system within the human uterine cervix and a role of NO in control of cervical function.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

T-cell transfer and cytokine/TCR gene deletion models in the study of inflammatory bowel disease.

Until recently there existed no appropriate immunological animal models for human inflammatory bowel diseases (IBD). Today a number of models, mostly in the mouse and rat, have proved useful in the study of several aspects of IBD, including the histopathology and the disease-inductive and -protective cell types, subsets and cytokines, for example CD4+ T cells, IFN gamma, IL-12, IL-2, IL-10 and TGF beta. Furthermore, these recent IBD models make it possible to examine various chemo- and immunotherapeutic approaches. This review focuses on IBD development in adoptive T-cell transfer models and in gene-deleted mice.

Animals↗
PubMed1996

The effect of pelvic nerve stimulation on recto-anal motility in the cat.

Rectal and anal motility responses to pharmacological manipulation of neuro-transmission and graded efferent electrical pelvic nerve stimulation were investigated in alpha-1-chloralose anaesthetized cats. N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of nitric oxide synthase, did not influence spontaneous rectal and anal motility. No significant change in anal pressure or rectal tone was observed after sectioning the pelvic nerves in animals pretreated with L-NNA. The effect of pelvic nerve stimulation on anal tone was varying and depended upon the intensity of stimulation and the prevailing anal tone. A reduction of anal tone on pelvic nerve stimulation was consistently converted to an increase of anal tone after pretreatment with L-NNA. The rectal response to pelvic nerve stimulation was unchanged by L-NNA. Residual increase of anal tone observed on pelvic nerve stimulation after L-NNA and noradrenergic blockade was partly sensitive to hexamethonium and abolished by atropine. The results suggest that there is no tonic influence on rectal and anal motility via nitric oxide mechanisms. On the other hand, the reduction of anal tone on high intensity pelvic nerve stimulation seemed to be dependent on the release of nitric oxide. An excitatory cholinergic component of the smooth muscle contractility of the feline anal canal, partly sensitive to hexamethonium, was demonstrated to be conveyed in the pelvic nerves.

Adrenergic Antagonists↗
PubMed1996

Sympathetic and VIP-ergic control of calcium and bicarbonate transport in the feline gall bladder mucosa in vivo.

The regulation of calcium ion absorption by the gall bladder mucosa may be important for gall stone formation but this process is poorly understood. In this study performed in anaesthetized cats, the gail bladder lumen was perfused by a buffer equilibrated with 4% CO2 in air. During basal conditions, the pH and the [Ca2+] x [CO3(2-)] ion product decreased in the buffer when passing through the gall bladder lumen. The net absorption of calcium ions and fluid was significantly enhanced by stimulation of the splanchnic nerves. Intravenous infusion of vasoactive intestinal peptide (VIP) increased pH and the [Ca2+] x [CO3(2-)] ion product significantly in the buffer during the passage through the gall bladder lumen. Moreover, the basal fluid absorption was reversed to a net fluid secretion. In view of the presence of noradrenergic and VIP-immunoreactive nerve fibres in the gall bladder wall, and VIP-receptors on the gall bladder epithelial cells, the study suggests the existence of neural control mechanisms influencing the transport of Ca2+ by the gall bladder mucosa. These may be important to reduce potential calcium lithogenicity in the gall bladder lumen.

Animals↗
PubMed1996

VIP-antiserum and indomethacin inhibit calcium and bicarbonate secretion by the inflamed feline gallbladder mucosa.

Ionized calcium (Ca2+) and bicarbonate (HCO(3)-) are important ions for gallstone formation. In the present study the effect of indomethacin and vasoactive intestinal peptide-antiserum (VIP-antiserum) on the Ca2+, HCO(3)- and fluid secretion in the inflamed gallbladder were tested in a validated experimental model in cats. The animals were studied in acute experiments 6 weeks after cystic duct ligation and gallstone implantation. During basal conditions there was a continuous secretion of Ca2+, HCO(3)- and fluid into the lumen of the inflamed gallbladder. Indomethacin and VIP-antiserum inhibited the Ca2+, HCO(3)- and fluid secretion across the inflamed gallbladder mucosa. Intraluminal amiloride inhibited the absorption of Ca2+, HCO(3)- and fluid after indomethacin infusion. An impaired absorption of Ca2+, HCO(3)- and fluid in the inflamed gallbladder is probably important for the solubility of calcium salts in the early stages of inflammation in the gallbladder mucosa.

Animals↗
PubMed1996

Role of nitric oxide in induction of inflammatory fluid secretion by the mucosa of the feline gallbladder.

BACKGROUND & AIMS: Nitric oxide is synthesized from L-arginine and is metabolized to nitrate and nitrite. This study evaluates the effects of a pharmacological blockade of NO synthesis on fluid transport by the inflamed gallbladder mucosa. METHODS: Experiments were performed in cats with cholecystitis and in control animals. NO synthase activity was measured in gallbladder tissue; the enzyme was characterized by immunoblotting techniques and localized by immunofluorescence. Fluid transport and release of nitrate and nitrite by the gallbladder mucosa and bile and bile salt secretion from the liver were registered simultaneously in vivo. RESULTS: Fluid secretion in inflamed gallbladders was reversed to a net absorption in response to the NO synthase blockers N omega-nitro-L-arginine and aminoguanidine, and formation of nitrate was reduced. The effects were reversed by L-arginine. Increased levels of inducible NO synthase in inflamed gallbladders were shown by immunoblotting, by immunofluorescence (mainly in macrophages), and by Ca(2+)-independent [3H]citrulline formation from [3H]arginine. The NO synthase blockers had no effect on gallbladder fluid transport in normal gallbladders. CONCLUSIONS: Increased levels of inducible NO synthase activity are shown in inflamed gallbladders, and a pharmacological blockade of this enzyme blocks fluid secretion and decreases nitrate release from the mucosa.

Analysis of Variance↗
PubMed1996

Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation.

Nitric oxide (NO) has emerged as one of several important intraovarian regulatory factors. In particular, NO has been implicated in the processes of ovulation and atresia-related apoptosis. The aim of the present study was to investigate the presence and distribution of the NO-generating nitric oxide synthase (NOS) enzymes in the ovary during follicular development, ovulation and luteal formation of the equine chorionic gonadotrophin (ECG)/human chorionic gonadotrophin (HCG)-primed rat. NADPH diaphorase activity was used as a histochemical marker for NOS within the ovary. Diaphorase reactivity was most abundant in the stroma (S) of the ovary and in the theca (T) layer of the follicle. In luteinized ovaries, weaker diaphorase reactivity was present within the corpora lutea (CL). Two different isoforms of NOS, the constitutively expressed endothelial NOS (eNOS) and the inducible isoform of NOS (iNOS), were immunolocalized in ovaries of immature rats and in ECG/HCG-primed rats during the periovulatory period from HCG injection until 2 days after ovulation. In addition, ovarian concentrations of eNOS and iNOS were quantified by immunoblotting. Immunoblotting with a monoclonal anti-eNOS antibody demonstrated the presence of eNOS mainly in the residual ovary (ROV) during the periovulatory period. In luteinized ovaries, higher concentrations of eNOS were seen in CL, while those in the ROV at this stage were lower than in the periovulatory ovary. Immature ovaries contained diminutive amounts of eNOS, detectable mostly in the ROV compartment. In contrast, iNOS was barely detectable during follicular development to the preovulatory stage. A slight elevation of iNOS was observed in the granulosa cells at 6 h after the HCG injection. The levels of iNOS during the luteal phase were also low. Immunohistochemical analysis using polyclonal eNOS and iNOS antibodies revealed the localization of these two isoforms primarily in the S and the T of the periovulatory ovary. In luteinized ovaries, positive immunoreactivity was also seen within the CL. With a monoclonal antibody against eNOS, intense immunoreactivity was observed in the S, T and within CL. There was a particularly strong staining in blood vessels. These data demonstrate the presence of an intraovarian NO-generating system. The localization of this system to the S, T and CL suggests a role for NO in the ovulatory process and in the regulation of CL function.

Animals↗
PubMed1996

The role of nitric oxide in the acetylcholine-induced relaxation of the feline internal anal sphincter, in vitro.

BACKGROUND: The relaxatory effect of acetylcholine was investigated on the feline internal anal sphincter (IAS), in vitro. RESULTS: Acetylcholine (10, 30, 100, and 1000 microM) caused a concentration-dependent relaxation of the same magnitude in strips from the proximal and distal IAS. The antagonist of nitric oxide synthase, N omega-nitro-L-arginine (L-NNA; 1, 10, and 100 microM), in a concentration-dependent and stereospecific manner, blocked the acetylcholine-induced relaxation, leaving a residual response of 10-30%. The blocking effect of L-NNA (100 microM) could not be shown in tissues that had been incubated with the substrate for nitric oxide synthase, L-arginine (1 mM). CONCLUSIONS: The present results suggest that the acetylcholine-induced relaxation of the IAS to a major extent is due to an activation of nitrergic, inhibitory motor neurons to the IAS.

Acetylcholine↗
PubMed1995

Reflex interaction from the urinary bladder and the rectum on anal motility in the cat.

The intrinsic recto-anal inhibitory reflex (RAIR) and the extrinsic vesico-anal excitatory reflex were studied in anaesthetized cats in order to explore the nervous components of anal pressure regulation. The magnitude of the RAIR was documented at varying levels of anal pressure. Minimal anal pressure during RAIR was positively correlated to anal pressure immediately prior to rectal distension. It was possible to elicit the vesico-anal excitatory reflex concomitantly with an ongoing RAIR. It was also possible to elicit a RAIR during the vesico-anal excitatory reflex. The magnitude of the pressor reflex response was not changed by concomitant activation of the inhibitory reflex and vice versa. This suggests an independent action on the internal anal sphincter (IAS) of the two reflexes. Spontaneous detrusor contractions were abolished by rectal distension. However, an escape phenomenon from this inhibition was observed, suggesting a spinal, associative, connection. The results support the concept of a direct action of both extrinsic and intrinsic nervous mechanisms on the smooth muscle of the IAS.

Anal Canal↗
PubMed1995

Anal and rectal motility responses to distension of the urinary bladder in man.

Recto-anal motility response to bladder distension was studied under general anaesthesia in 12 patients undergoing intestinal resection for Crohn's disease of the small intestine or colonic cancer. The effect of epidural anaesthesia on anal tone and on the motility response to bladder distension was studied in six of these patients. An anal pressure increase on bladder distension was observed in all individuals. No motility response was noted in the rectum. The anal pressure response to bladder distension was abolished by epidural anaesthesia. It was concluded that anal pressure in man under general anaesthesia was tonically influenced by the thoracolumbar sympathetic outflow. An excitatory vesico-anal reflex was demonstrated. It appears as this reflex is mediated via the spinal cord.

Adult↗
PubMed1994

Anal and rectal motility responses to distension of the urinary bladder in the cat.

The neural pathways and possible transmission mechanisms of the integrated autonomic nervous control of the urinary bladder and anorectum, were investigated in chloralose anaesthetized cats. Bladder distension and spontaneous detrusor contractions increased internal anal sphincter-tone, a response which was blocked by an alpha-adrenoceptor antagonist. Moreover, a nicotinic transmission step was present. Both the afferent and efferent limbs of the reflex were conveyed in the postganglionic hypogastric nerves and the preganglionic lumbar splanchnic nerves. Intact connection with the central nervous system was therefore essential. Contrasting to the specific reflex response in the internal anal sphincter, bladder distension also elicited a nociceptive vaso-pressor response. Rectal motility appeared to be unaffected by bladder distension.

Adrenal Glands↗
PubMed1993

Possible role of the autonomic nervous system in sphincter impairment after restorative proctocolectomy.

Peroperative manometry was performed in 12 patients operated on with endoanal proctectomy and a hand-sewn pouch-anal anastomosis and in 12 in whom proctectomy was performed entirely from above, with the ileal pouch stapled to the top of the anal canal. Results from both groups showed that division of the superior rectal artery reduced the median (95 per cent confidence interval (c.i.)) resting anal pressure from 77.5 (69.9-83.3) mmHg to 64.5 (55.2-70.0) mmHg (P < 0.01). Complete rectal mobilization to the pelvic floor decreased resting pressure by an additional 22 per cent, to a median of 50.0 (95 per cent c.i. 40.1-53.5) mmHg (P < 0.01). After completion of anastomosis, irrespective of the operative technique used, a further decline in median pressure to 35.0 (95 per cent c.i. 26.0-47.7) mmHg could be demonstrated (P < 0.05). This study indicates that anal sphincter pressure is reduced to a similar extent after hand-sewn and stapled anastomoses. Injury to the autonomic nervous supply to the anal sphincter mechanism might be the major cause for this reduction.

Adult↗