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Biomedical subjects

G Godlewski

Publications and source records attributed to G Godlewski.

At least 37 records · Page 2Linked to original sources

Inhibitory H3 receptors on sympathetic nerves of the pithed rat: activation by endogenous histamine and operation in spontaneously hypertensive rats.

Our previous results demonstrate the occurrence of presynaptic inhibitory histamine H3 receptors on sympathetic neurons innervating resistance vessels of the pithed rat. The present study, in which new H3 receptor ligands with increased potency and selectivity (imetit, clobenpropit) were used, was designed to further explore the role of H3 receptors in the regulation of the rat cardiovascular system. In particular we were interested whether these receptors may be activated by endogenous histamine and whether they are detectable in an experimental model of hypertension. All experiments were performed on pithed and vagotomized rats treated with rauwolscine 1 mumol/kg. In normotensive Wistar rats the electrical (1 Hz, 1 ms, 50 V for 20 s) stimulation of the preganglionic sympathetic nerve fibres increased diastolic blood pressure by about 35 mmHg. Two H3 receptor agonists, R-(-)-alpha-methylhistamine and imetit, inhibited the electrically induced increase in diastolic blood pressure in a dose-dependent manner. The maximal effect (about 25%) was obtained for R-(-)-alpha-methylhistamine at about 10 mumol/kg and for imetit at about 1 mumol/kg. Two H3 receptor antagonists, thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg, attenuated the inhibitory effect of imetit. The neurogenic vasopressor response was increased by about 15% by thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg and decreased by 25% by the histamine methyltransferase inhibitor metoprine 37 mumol/kg. R-(-)-alpha-Methylhistamine, imetit, thioperamide, clobenpropit and metoprine did not affect the vasopressor response to exogenously added noradrenaline 0.01 mumol/kg (which increased diastolic blood pressure by about 40 mmHg). Metoprine had only a very low affinity for H3 binding sites (labelled by 3H-N alpha-methylhistamine; pKi 4.46). In pithed Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats, electrical (1 Hz, 1 ms, 50 V for 10 s) stimulation increased diastolic blood pressure by 28 and 37 mmHg, respectively. Imetit inhibited the neurogenic vasopressor response to about the same extent in WKY and SHR rats (maximal effect of about 30%). The inhibitory influence of imetit was diminished by thioperamide 1 mumol/kg to about the same degree in rats of either strain. The present study confirms the occurrence of presynaptic H3 receptors on sympathetic nerve fibres involved in the inhibition of the neurogenic vasopressor response. Moreover, it demonstrates that these H3 receptors are probably activated by endogenous histamine and appear to be operative in hypertension.

Adrenergic Fibers↗

Cannabinoid CB1 receptor-mediated inhibition of the neurogenic vasopressor response in the pithed rat.

The effects of two cannabinoid receptor agonists, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4- benzoxazin-yl]-(1-naphthalenyl)-methanone (WIN 55,212-2) and (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydr oxypropyl)-cyclohexanol (CP-55,940), were studied on (i) the vasopressor response elicited in pithed rats by electrical stimulation of the sympathetic outflow and (ii) the release of 3H-noradrenaline and the vasoconstriction elicited in isolated rat tail arteries by transmural electrical stimulation. In pithed rats, the electrical (1 Hz for 10 s) stimulation of the preganglionic sympathetic nerve fibres increased diastolic blood pressure by about 30 mmHg. This neurogenic vasopressor response (which under the conditions of our study was almost exclusively due to the release of catecholamines) was decreased by WIN 55-212,2 and CP-55,940 in a dose-dependent manner (inhibition by WIN 55,212-2 and CP-55,940, 0.1 micromol/kg each, about 25-30%). The inhibition was identical in adrenalectomized rats and in animals with intact adrenals. The inhibitory action of WIN 55,212-2 and CP-55,940 was abolished by a dose of 0.03 micromol/kg of the CB1 receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR 141716), which, by itself, had no effect. WIN 55,212-2, CP-55,940 and SR 141716 failed to affect the vasopressor response to exogenous noradrenaline (1 nmol/kg), which also increased diastolic blood pressure by about 30 mmHg. In isolated rat tail arteries, the electrically (0.4 Hz) evoked tritium overflow and vasoconstriction were not modified by WIN 55,212-2 and CP-55,940 (1 micromol/l each). In conclusion, the neurogenic vasopressor response in the pithed rat can be modulated via cannabinoid CB1 receptors probably located presynaptically on the postganglionic sympathetic nerve fibres innervating resistance vessels.

Action Potentials↗

Mechanism of aneurysm formation after 830-nm diode-laser-assisted microarterial anastomosis.

OBJECTIVE: The process of aneurysm formation after laser welding is described. SUMMARY BACKGROUND DATA: The mechanism of aneurysm formation after laser-assisted microarterial anastomosis is presently unclear. METHODS: A series of 830-nm diode-laser-assisted longitudinal aortorrhophy with a condition of 400 to 500 J/mm2 for 1 cm length of anastomosis versus conventional manual anastomoses were performed in 90 Wistar rats. To compare this technique with normal media process, a histologic examination of aneurysm formation was conducted. RESULTS AND CONCLUSIONS: The results show that there are two important factors that cause aneurysm formation after laser-assisted anastomosis: 1) the vessel wall is damaged by laser heating; 2) proliferation of collagen fiber at the adventitia is absent during media reconstruction.

Anastomosis, Surgical↗

Identification of histamine H3 receptors in the tail artery from normotensive and spontaneously hypertensive rats.

We examined the possible existence of prejunctional histamine H3 receptors on sympathetic nerve fibers innervating rat tail artery. The stimulation-evoked tritium outflow from isolated vessels preincubated with [3H]-noradrenaline and perfused/superfused in the presence of the alpha2-adrenoceptor antagonist rauwolscine, 3 microM, was inhibited by histamine 10 microM (by 8%) and the H3 agonists R-(-)-alpha-methylhistamine, 10 microM (by 18%), and imetit, 0.1-10 microM (by < or =20%). The inhibitory effect of imetit, which did not occur in the absence of rauwolscine, was counteracted by thioperamide, 1 microM. In the presence of rauwolscine, 3 microM, the inhibitory effect of imetit also occurred when the current strength or the Ca2+ concentration in the medium was reduced to compensate for the increase in tritium overflow elicited by rauwolscine, indicating that the inhibitory action of imetit is not associated with the increase in noradrenaline release produced by rauwolscine. In spontaneously hypertensive rats (SHRs), imetit also inhibited the overflow of tritium. This inhibitory effect was comparable to that observed in Wistar-Kyoto (WKY) rats and indicates that the sympathetic nerves of the rat tail artery in SHRs, like those in normotensive rats, are endowed with prejunctional histamine H3 receptors.

Adrenergic alpha-2 Receptor Antagonists↗

Liver development in the rat during the embryonic period (Carnegie stages 15-23).

Hepatic and biliary structures appearing during embryonic Carnegie stages 15-23 were analyzed in OFA rat embryos. The group of rats with crown rump length 7.5-16 mm and 12.8-16 days after coitus yielded 55 specimens (23 of stages 15-16, 20 of stages 17-18, 9 of stages 19-22 and 3 of stage 23). The embryos were submitted to serial histological sections with graphic reconstructions. From stage 15 to the end of the embryonic period, the hepatic gland and its vascular channels (transverse portal sinus and hepatocardiac veins) presented considerable enlargement while hematopoietic function appeared. At stage 17, occlusion due to epithelial proliferation was evident in the hepatic duct. At stage 18, the duct became recanalized and assured the continuity between liver cells and gut. From stage 18 to 23, biliary ductules developed in periportal connective tissue forming ductal plates which received biliary caniculi. Except for the gall-bladder which is never present in the rat, similarity and presence of the same hepatic structures in man and in the rat during the embryonic period stages 15-23 suggest that the rat is a good experimental model for liver development and will be useful in the understanding of congenital anomalies.

Animals↗

[Pneumatosis cystoides of the colon. Apropos of 7 cases].

Seven cases of pneumatosis cystoides intestinalis affecting the colon (PKC) revealed 5 times by a nonspecific symtomatology and 2 times by an occlusion were reported. In three of the patients the disease was found as a primary idiopathic form free of clinical antecedents. In 4 of the patients the pneumatosis was found to be secondary to a pulmonary disease, a gastric ulcer, a connectivite of a corticotherapy. The PKC was generally diagnosed either by barium enema or by computed tomography and less frequently by colonoscopy with deep biopsy allowing differential diagnosis with colonic polyposis. The mechanism and etiology of the PKC were not fully understood. The illness is a benign condition that often responds to a conservative management--i.e. abstention, oxygenotherapy, diet or antibiotherapy- or exceptionally to surgical colonic resection in case of acute complication.

Aged↗

Facilitation by substance P and inhibition by (+)-tubocurarine of the 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats.

The influence of substance P 3 (microgram/kg) and (+)-tubocurarine (850 micrograms/kg) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. The Bezold-Jarisch reflex was induced by the 5-HT3 receptor agonist phenylbiguanide (0.3, 1, 3 and 10 micrograms/kg i.v.) and by capsaicin (10 micrograms/kg i.v.). The 5-HT3 receptor antagonist ondansetron (10 micrograms/kg) abolished the phenylbiguanide- but not the capsaicin-stimulated bradycardia, indicating that phenylbiguanide and capsaicin act via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Substance P significantly potentiated the phenylbiguanide- but not the capsaicin-induced decrease in heart rate. Also, when the phenylbiguanide-induced response was amplified by substance P, it was abolished by ondansetron. (+)-Tubocurarine inhibited the phenylbiguanide-induced bradycardia, but did not affect the capsaicin-stimulated decrease in heart rate. Our results demonstrate that substance P potentiates but (+)-tubocurarine inhibits the 5-HT3 receptor-mediated Bezold-Jarisch reflex. Both effects are probably due to direct influences of the drugs on the 5-HT3 receptors on sensory vagal nerves in the heart.

Animals↗

Interstitial diode laser hyperthermia in the treatment of subcutaneous tumor.

BACKGROUND AND OBJECTIVE: Interstitial Laser Hyperthermia (ILH) has been investigated since the early 80s in the treatment of deep seated tumors. The purpose of this study was to evaluate the efficiency of diode ILH (830 nm) in a subcutaneous tumor model. STUDY DESIGN/MATERIALS AND METHOD: The antitumoral effect of diode ILH was assessed in a randomized study performed on 80 Swiss nu/nu mice. The tumor model was a subcutaneously implanted HT29 colonic carcinoma. The animals were assigned to four groups of 20 mice: Groups 1 and 3 were treated by ILH, groups 2 and 4 were not treated (control groups). Tumors were removed on day 3 in groups 1 and 2, and on day 30 in groups 3 and 4. The treatment was performed on tumors of 8 mm in diameter and a volume of 140 mm3. A laser irradiation of 360 J (power: 0.2 W; irradiation time: 1800 s) was delivered through a 300 microns optical fiber implanted in the tumor. The laser parameters insured temperatures of 46 degrees C in the central part of the tumor and 42 degrees C at the periphery. Tumor features were evaluated on day 3 and day 30. RESULTS: Untreated tumors grew rapidly up to a mean volume of 241 mm3 on day 3 (group 2) and 2,000 mm3 on day 30 (group 4). Treated tumors regressed to a mean volume of 32 mm3 on day 3 (group 1). On day 30, 40% of the tumors had totally disappeared and 60% showed partial response with small and peripheral residual tumor of 172 mm3 on an average, as to say 11.2 times smaller than in group 4. CONCLUSION: ILH with a low power 830 nm diode laser is an efficient treatment of subcutaneous tumor model. Partial responses are attributed to an insufficient heating at the tumor periphery. More precise control of the peripheral tumor temperature will improve the ILH results.

Animals↗

Caffeine as a metabolic probe: NAT2 phenotyping.

1. Caffeine has been used to determine acetylator phenotype for some 15 years but the interpretation of metabolic ratios with this substance raises theoretical and methodological issues. 2. N-acetyltransferase type 2 (NAT2) status was assessed in 23 young healthy subjects using both caffeine overnight and spot urine samples, and sulphadimidine. 3. Frequency distribution analysis of the metabolic ratios of NAT2, indicated two distinct groups for sulphadimidine, and for caffeine spot but not overnight samples. Spearman's rank correlation values were low indicating differences between the data sets for sulphadimidine and spot caffeine samples. Correlation between the two urine collection periods for caffeine was poor. 4. The complex metabolism of caffeine may compromise its value as a probe for determining acetylator phenotype until the effects of important variables are better understood.

Adult↗

Inhibitory effect of ethanol on the 5-hydroxytryptamine-induced Bezold-Jarisch reflex--involvement of peripheral 5-HT3 receptors.

The influence of ethanol (0.5, 1.0 and 2.0 g/kg i.p.) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. 5-Hydroxytryptamine (serotonin; 5-HT; 1, 3, 10 and 30 micrograms/kg i.v.) and capsaicin (1, 3 and 10 micrograms/kg i.v.) reflexly decreased heart rate in a dose-dependent manner. The 5-HT3 receptor antagonist ondansetron 10 micrograms/kg i.v. abolished the 5-HT- but not the capsaicin-stimulated bradycardia, indicating that 5-HT and capsaicin acted via different trigger mechanisms (5-HT3 receptor-dependent and -independent, respectively). Ethanol at 1.0 and 2.0 g/kg i.p. inhibited in a dose-dependent manner (by 20-45%) the 5-HT- but not the capsaicin-stimulated decrease in heart rate. Our results demonstrate that the inhibitory effect of ethanol on the 5-HT3 receptor-mediated Bezold-Jarisch reflex may be related to the direct effect of ethanol on 5-HT3 receptors on sensory vagal nerves in the heart.

Animals↗

Scanning electron microscopy of microarterial anastomoses with a diode laser: comparison with conventional manual suture.

A diode-laser (830 nm)-assisted carotid artery end-to-end microanastomosis (LAMA) and a contralateral manual suture anastomosis (CMA) were performed in 70 Wistar rats. The vessel sealing was performed on the left carotid by laser pulses (average 3) of 500 mW power and 4.5 sec exposure time, the beam being focused on a spot of 300 microns diameter (700 W/cm2). The CMA was achieved on the right carotid by six 10-0 stitches. From day 0 to day 210, 40 specimens underwent scanning electron microscopy. The laser impact produced a wall injury of 100 microns in width, with an immediate sealing effect due to protein denaturation and collagen fusion of media and adventitia. The anastomosis became re-endothelialized by day 3, while the longitudinal arrangement of the endothelial cells was restored from day 10 on. In the long term, a thick collagenous meshwork of collagen and elastic fibers maintained the strength of the media, while normal endothelium covered the anastomosis. Inversely, after CMA vessel repair was delayed, and the anastomotic line was more irregular and underlined by medial fibrotic scar. In both anastomoses, the patency rate was 93 percent, with nonlethal complications. The advantages of LAMA vs. CMA were: shorter operating time (13 min/22 min), reduced intraoperative trauma, better healing of endothelium, and a miniaturization of the laser source well adapted to microsurgery.

Anastomosis, Surgical↗

EP3 receptor-mediated inhibition of the neurogenic vasopressor response in pithed rats.

In pithed rats, we studied the effects of prostaglandin E2 and of subtype-selective prostaglandin E receptor (EP receptor) ligands on the rise in blood pressure induced by electrical stimulation of the preganglionic sympathetic nerves. Prostaglandin E2, the EP1/EP3 receptor agonist sulprostone and the EP2/EP3 receptor agonist misoprostol inhibited the electrically induced increase in diastolic blood pressure (rank order of potencies sulprostone > or = misoprostol > or = prostaglandin E2); the rise in blood pressure induced by exogenously added noradrenaline was not affected by these compounds. The inhibitory effect of sulprostone on the electrically induced vasopressor response was not significantly changed by indomethacin. Iloprost (an agonist at EP1 and prostacyclin receptors (IP receptors)) failed to affect the electrically evoked increase in blood pressure. The present study suggests that prostaglandin E2 inhibits the release of catecholamines in pithed rats via prostanoid receptors of the EP3 subtype, probably located presynaptically on the postganglionic sympathetic nerve fibres.

Alprostadil↗

Microarterial anastomosis using a noncontact diode laser versus a control study.

A series of direct carotid end-to-end laser anastomosis vs. direct manual suture was carried out on a series of 70 Wistar rats (mean weight 260 g). Both common carotids (0.8-1.2 mm) were sectioned and repaired. The left side (n = 70) was submitted to laser-assisted microvascular anastomosis (LAMA) performed by means of a diode laser device (wavelength 830 nm and power output 3 W in continuous wave) without chromophore. The right side (n = 70) underwent a control manual suture (CMA). The diode laser energy was delivered into a micromanipulator coupled to a Zeiss operating microscope with a focused spot of 300 microns in diameter. After placement of three 10.0 stitches for edge coaptation, the LAMA was achieved using laser shots (average 3) of 500 mW power, 4.5 s duration, and 700 W/cm2 irradiance each. The CMA was performed by means of six 10.0 stitches. The good vascular flow was confirmed by Doppler spectral analysis (n = 466) carried out from day 0 to day 90. Light and scanning electron microscopy (n = 82) showed that re-endothelialization after LAMA was gaining ground on day 3, whereas collagenous network developed in the media scar by day 10. In contrast, after CMA the arterial repair was delayed on day 20, inducing a media fibrotic scar. The patency rate was 93% in both anastomoses. The shorter operating time (13 min for LAMA vs. 22 min for CMA) and the noncontact laser technique are the main intraoperative advantages. The technical benefits of the diode laser are pointed out.

Anastomosis, Surgical↗

Tubal sterilization by selective catheterization in an animal model.

RATIONAL AND OBJECTIVES: The feasibility of tubal occlusion by selective salpingography was tested in an animal model; three novel occluding materials also were tested for this application. METHODS: Unilateral selective salpingography was performed in three groups of six rabbits; fallopian tubes were embolized with ethanol (group 1), a hydrogel (group 2), or an occluding emulsion (Ethibloc, Laboratoire Princeps, Neuilly sur Seine, France) (group 3). Animals were killed 2 days or 30 days after the procedure, according to randomization; tubal patency and histologic modifications were evaluated. RESULTS: Selective tubal catheterization was obtained in 100% of the cases. In group 1, no satisfactory occlusion was obtained; in group 2, 65% of the tubes were occluded with little histologic damage; in group 3, 80% of the tubes were occluded, but significant inflammation and tissue necrosis were noted. CONCLUSION: Selective salpingography proved a suitable method for gaining access to the fallopian tube and allowed selective injection of occluding materials. More research is needed to determine a suitable occluding material, focusing on biocompatibility and on long-term efficacy.

Animals↗

Static morphometric bases for CT identification and evaluation of the outflow chamber of the left ventricle. Preliminary study in formalin-fixed heart.

A static morphometric study of the outflow chamber of the left ventricle (OCLV) was investigated in a series of 10 formalin-fixed hearts. A spatial reconstruction of the shape and the volume of the OCLV was carried out by means of a Somaton Plus TR4 Tomodensitometer (Siemens). The technic allows evaluation of the surface of the aortic and the mitral orifices and visualization of the three-dimensional OCLV and LV morphology, as well as calculation of their volumes. The limits of the technic in the dynamic study of the OCLV are presented.

Adult↗

[Cystic dystrophy in an aberrant pancreas. Contribution of computerized tomography and MRI].

Case report of a cystic dystrophia appearing in an ectopic pancreas. The clinical diagnosis was preoperatively suspected by the findings of CT scan revealing a tumor located in the wall of the duodenum and by the data of MRI indicating its cystic and fibrotic structure. A focus of reacting pancreatitis was found in the vicinity of the cystic dystrophia while the remaining pancreas was normal. The surgical treatment was a duodenopancreatectomy, justified by the potential risks of complications.

Cysts↗