Galanin receptor 3--a potential target for acute pancreatitis therapy.

BACKGROUND: Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub-types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP. METHODS: Galanin receptor expression in murine whole pancreas, acinar, and islet cells was quantified by polymerase chain reaction amplification of reverse-transcribed RNA for mRNA, Western blot analysis for protein and in situ hybridization for GALR localization. Isolated acinar cells were used to determine galanin's effect on amylase secretion. Acute pancreatitis was induced in mice by caerulein injections. Mice, with and without AP, were treated with the highly selective GALR2 antagonist M871, or the specific GALR3 antagonist SNAP-37889. Indices of AP were measured at 12 h. KEY RESULTS: Murine pancreas expresses mRNA for GALRs. In islets the expression of all GALR are comparable, whereas in acinar cells GALR3 is predominantly expressed. Western blot analysis confirmed that the GALR proteins are expressed by acinar cells. In situ hybridization analysis confirmed that GALR3 mRNA is present in islet and acinar cells, while mRNA for GALR1 and 2 is confined to islets. Galanin did not influence basal and caerulein-stimulated amylase release from acinar cells. M871 treatment reduced some, whereas SNAP-37889 treatment reduced all indices of AP (by 40-80%). CONCLUSIONS & INFERENCES: Galanin receptor mRNA and protein are expressed in mouse pancreas, with GALR3 mRNA predominating. GALR3 antagonism reduced the severity of AP whereas GALR2 antagonism was less effective. GALR3 is a potential target for treatment of AP.

Galanin receptor antagonist m35 but not m40 or c7 ameliorates cerulein-induced acute pancreatitis in mice.

BACKGROUND/AIMS: We compared the galanin antagonists C7, M35, M40 and galantide, for their ability to ameliorate acute pancreatitis (AP). METHODS: Galanin antagonists were co-administered with 7 hourly cerulein injections used to induce AP. Plasma amylase and lipase activities were measured as indices of AP, and pancreata were harvested at 12 h for histological examination and estimation of myeloperoxidase (MPO) activity. RESULTS: Treatment with galantide, M35 and C7 ameliorated the AP-induced plasma hyperenzymemia by 40-75%. Administration of M40 did not significantly alter plasma hyperenzymemia. Galantide, M35 and M40 significantly reduced the pancreatic MPO activity by 65-80%, whereas C7 increased MPO activity. Galantide and M35 but not C7 or M40 treatment significantly reduced the AP-induced necrosis score by 30-50% compared to the AP alone group. C7 alone increased plasma lipase activity and the pancreatic necrosis score compared with saline treatment alone, whereas the other antagonists were without effect. CONCLUSION: Galantide and M35 ameliorated the severity of AP, but M40 and C7 had mixed effects. Complex galanin pathways may be involved in cerulein-induced AP. M35 and galantide are potential therapeutic peptides for the treatment of AP and further evaluation should be considered. and IAP.

A virtual reality 3D jigsaw for teaching anatomy.

Virtual Reality has some advantages over traditional teaching and learning media. Here we describe a VR Jigsaw which uses a novel interface to facilitate learning the anatomy of the skull. A small trial was performed which indicates that the software succeeds at engaging students and suggests that their comprehension of complex 3D structures was improved.

Sphincter of Oddi function in the Australian brush-tailed possum is inhibited by intragastric ethanol.

The role of sphincter of Oddi (SO) function in alcoholic acute pancreatitis (AP) is unclear. We aimed to compare the effect of i.v. and intragastric (IG) ethanol on SO function (i.e. trans-sphincteric flow; TSF) and investigate possible neural mechanisms. The involvement of gastric mucosal damage was also investigated by pretreatment with pantoprazole. In anaesthetized Australian possums, blood pressure (BP), TSF and blood ethanol concentrations were measured after i.v. or IG ethanol. Possums were subjected to acute vagotomy, atropine, L-nitro arginine methyl ester (L-NAME) or pantoprazole pretreatment prior to IG ethanol. BP was not significantly altered by ethanol. Ethanol decreased TSF in a dose and route-dependent manner. The lowest dose of IG ethanol reduced TSF but this response was not duplicated by i.v. ethanol producing the same blood ethanol concentrations. Acute vagotomy, atropine or L-NAME pretreatment blocked the ethanol-induced decrease in TSF and simultaneously suppressed the blood ethanol concentration. Pantoprazole pretreatment reduced the TSF response and blood ethanol concentrations implicating mechanisms induced by gastric mucosal damage. We conclude that ethanol (and/or its metabolites) reduces TSF via humoral and neural mechanisms involving vagal pathways, muscarinic receptors and nitric oxide. Reduced TSF could contribute to the onset of AP.

A systematic review of common conservative therapies for arm lymphoedema secondary to breast cancer treatment.

Secondary arm lymphoedema is a chronic and distressing condition which affects a significant number of women who undergo breast cancer treatment. A number of health professional and patient instigated conservative therapies have been developed to help with this condition, but their comparative benefits are not clearly known. This systematic review undertook a broad investigation of commonly instigated conservative therapies for secondary arm lymphoedema including; complex physical therapy, manual lymphatic drainage, pneumatic pumps, oral pharmaceuticals, low level laser therapy, compression bandaging and garments, limb exercises and limb elevation. It was found that the more intensive and health professional based therapies, such as complex physical therapy, manual lymphatic drainage, pneumatic pump and laser therapy generally yielded the greater volume reductions, whilst self instigated therapies such as compression garment wear, exercises and limb elevation yielded smaller reductions. All conservative therapies produced improvements in subjective arm symptoms and quality of life issues, where these were measured. Despite the identified benefits, there is still the need for large scale, high level clinical trials in this area.

Long-term progestin-only contraceptives result in reduced endometrial blood flow and oxidative stress.

CONTEXT: Because of their safety and efficacy, long-term progestin-only contraceptives (LTPOCs) are well-suited for women with restricted access to health care. However, abnormal uterine bleeding (AUB) causes half of all users to discontinue therapy within 12 months. Endometria of LTPOC-treated patients display aberrant angiogenesis with abnormally enlarged, thin-walled, fragile blood vessels, inflammation, and focal hemorrhage. In this study, similar effects were observed with a new third-generation implantable LTPOC. OBJECTIVE: We hypothesized that LTPOC reduces uterine and endometrial blood flow, leading to hypoxia/reperfusion, which triggers the generation of reactive oxygen species. The latter induce aberrant angiogenesis, causing AUB. DESIGN: Endometrial perfusion was measured by laser-Doppler fluxmetry in women requesting LTPOCs. Endometrial biopsies were obtained for in vivo and in vitro experiments. SETTING: The study was conducted in the Yale University School of Medicine and Family-Planning Center in Western Australia. PATIENTS: Seven women 18 yr or older requesting implantable LTPOCs were recruited in Western Australia. INTERVENTION: Women received etonorgestrel implants. MAIN OUTCOME: LTPOC treatment resulted in reduced endometrial perfusion and increased endometrial oxidative damage. CONCLUSIONS: We propose that LTPOCs result in hypoxia reperfusion, which leads to aberrant angiogenesis resulting in AUB.

The effect of gentle arm exercise and deep breathing on secondary arm lymphedema.

The aim of this study was to explore the benefits of gentle arm exercise combined with deep breathing for secondary arm lymphedema. 38 women participated in 10 minutes of standardized arm exercise and deep breathing and were measured every 10 minutes for 1 hour, then 24 hours and 1 week post regime. A smaller cohort of 24 women continued the 10 minute exercise regime morning and evening for 1 month, with measurements being repeated at the end of this time. Directly after performing the regime, there was a reduction in arm volume of 52 mls (5.8%), with the reduction being sustained at 30 minutes (50 mls, 5.3%). Even though participants were told not to further do the exercise, at 24 hours the volume reduction was 46 mls (4.3%) and at 1 week, 33 mls (3.5%). At the one month follow-up, the reduction was 101 mls (9.0%). All reductions were statistically significant. Reported arm heaviness and tightness also statistically significantly decreased directly after the regime with the reduction in tightness being sustained at 24 hours. The reduction in heaviness was sustained at 24 hours, 1 week, and even one month after the program. Perceived limb size was significantly reduced at 1 week and at the 1 month follow-up. There was also a significant improvement in the anterior thorax tonometry reading at the 1 month follow-up.

The Sun Ancon Chi Machine Aerobic Exerciser: a new patient focused, home based therapy for people with chronic secondary leg lymphedema.

A significant proportion of those who survive lower torso cancer treatments will go on to develop clinically discernible bilateral or unilateral leg lymphedema. Although beneficial treatments exist for this condition, many are expensive and involve visits to outpatient clinics or allied health professionals--making the patient dependent upon others for treatment and maintenance. This clinical trial tested the efficacy of the Sun Ancon Chi Machine Aerobic Exerciser, a home based therapy that delivered both elevation and passive exercise to the legs. This machine was used in the participant's home according to a set regime with measurements being taken immediately before trial commencement, at weekly intervals and then 1 month after treatment cessation. After a three week treatment period there were statistically significant reductions in total leg volume and fluids, whole body extracellular fluid, weight and subjective leg symptoms. Lymphscintigraphy in a sub-group of patients suggested an increase in lymphatic transport in some individuals. Although some of the fluid and symptoms had returned at the 1 month follow up, none of the parameters had returned to pre-treatment levels. This finding indicates that this equipment may have ongoing beneficial effects. This clinical trial demonstrates that the Sun Ancon Chi Machine Aerobic Exerciser is an effective adjunct therapy that can be used in the patient's own home.

Endothelial distribution of the membrane water channel molecule aquaporin-1: implications for tissue and lymph fluid physiology?

BACKGROUND: Aquaporin-1 (AQ-1) is a transmembrane water channel protein reportedly expressed in continuous capillary endothelium and intestinal lacteals. We investigated endothelial AQ-1 expression in rat intestine and mesentery, and also in lymph nodes. METHODS AND RESULTS: Rat intestine, mesentery, and lymph nodes were immunolabeled for AQ-1, revealing membrane expression in endothelial cells of vascular continuous capillaries and venules, and of initial and conducting lymphatics. Blood vessel profiles were identified with RECA-1 and circulating FITC-albumin. In nodes, capillaries and high endothelium venules (HEVs) showed AQ-1 labeling, as did intranodal lymphatic sinusoidal endothelium and reticular cells. CONCLUSIONS: The labeling pattern of vessels with RECA-1, AQ-1, circulated FITC albumin, plus elastin autofluorescence permitted identification of arteriolar, continuous, and fenestrated capillaries and lymphatic vessels in tissue sections. Strong AQ-1 expression in continuous microvascular and initial lymphatic endothelium suggests its possible involvement in tissue fluid exchange between plasma and interstitial fluid, and perhaps between interstitial fluid and initial lymph. Endothelial AQ-1 expression was strong in lymphatic sinusoidal endothelium and intense in HEVs. This described endothelial AQ-1 expression has potential implications for tissue fluid physiology. Lymph protein is known to concentrate in lymph nodes by fluid loss, so AQ-1 may facilitate lymph to plasma water flux. Starling forces may not drive this flux, and we discuss a possible osmotic mechanism; consequently we hypothesize a suite of ion pumps/channels/exchangers/cotransporters in nodal vascular (probably HEV) endothelium, acting as a net ion pump from lymph to plasma, with water following osmotically.

Effects of acute pancreatic duct obstruction on pancreatic perfusion: implication of acute pancreatic duct decompression.

BACKGROUND: Acute pancreatitis can result in pancreatic ischaemia and necrosis. Pancreatic duct (PD) obstruction may be the first step causing ischaemia in acute pancreatitis. Nitric oxide donors can attenuate acute pancreatitis through improvement in compromised pancreatic perfusion (PP). In this study, we determined if (1) PD obstruction altered PP and (2) PD decompression or L-arginine administration reversed this change. METHODS: Fifteen Australian possums were randomly assigned to two groups: Animals in group A (n = 6) were subjected to 30 min of PD obstruction and 60 min of PD decompression. Animals in group B (n = 9) were subjected to 120 min PD ligation and 60 min PD decompression. A subset group B (n = 6) were subjected to intravenous L-arginine (100 microg/kg) at the end of 120 min of ligation and at the end of PD decompression. The PP (Laser Doppler fluxmetry), PD pressure and blood pressure were continuously monitored. RESULTS: PD pressure increased from 2.9 +/- 2.5 to 18.1 +/- 4.9 mmHg following PD ligation. PP was reduced to 67.1% +/- 4.5% (P<0.01) and 46.2% +/- 7.5% (P<0.001) of baseline following 30 and 120 min of PD ligation, respectively. Following 60 min of PD decompression, PP was restored to 89.1% +/- 13.4% (P<0.02) of the baseline in the 30-min group. However, following 120 min PD ligation, PP remained depressed. L-arginine administration after 120 min of PD ligation transiently increased PP from 46.2% +/- 7.5% to 81.1% +/- 8.6% (P<0.03) of baseline. This effect was reproduced if L-arginine was administered at the end of decompression (P<0.05). CONCLUSION: In patients with acute pancreatitis due to obstructive causes, early decompression of the PD may prevent early pancreatic ischaemia.

Combined opto-electronic perometry and bioimpedance to measure objectively the effectiveness of a new treatment intervention for chronic secondary leg lymphedema.

Secondary lymphedema of the legs is a common sequela of patients treated for cancer of the reproductive, gastrointestinal, urinary systems and melanoma. From a clinical and research perspective it is of utmost importance to use techniques that objectively quantify leg volume and fluid composition as an indicator of lymphedema severity and response to treatment. Two techniques often used in both the clinical and research setting are leg perometry and multi-frequency bioimpedance. Although both techniques have been extensively validated, this trial aimed to cross correlate both measurement techniques to ascertain whether each or both could be used reliably for measurement of leg lymphedema. These measurements were utilized throughout a clinical trial that assessed the effectiveness of a new home based treatment program in the form of the Sun Ancon Aerobic Exerciser. This machine delivered both elevation and passive exercise to the legs, with participants using the machine over a three week period during which time their leg volumes were measured using both perometry and bioimpedance. The results demonstrated that leg volume measurements decreased using both perometry and bioimpedance. The reduction in body extracellular fluid as measured by bioimpedance correlated well with a reduction in leg volume as measured by perometry. Bioimpedance also recorded a reduction in weight, which was correlated with the reduction in leg volume as measured by perometry. This trial confirms that perometry and bioimpedance were both effective in independently showing a reduction in leg lymphedema using the Aerobic Exerciser therapy, and that both methods can be reliably used to measure and follow leg lymphedema.

Changes in intrafollicular pressure in the rat ovary by nitric oxide and by alteration of systemic blood pressure.

BACKGROUND: ovulation is associated with degradation of the follicular apex vasodilatation and increased permeability of ovarian vessels. These changes may maintain or increase intrafollicular pressure (IFP) at ovulation to cause rupture of the follicular wall. OBJECTIVE: to investigate the possible regulation of IFP during the ovulatory process. STUDY DESIGN: immature Sprague-Dawley rats were primed with pregnant mare serum gonadotrophin (PMSG; 10IU) and given hCG (10IU) 48h later. The ovary was exposed 48-60h after PMSG, micropipette inserted into the Graafian follicle and the IFP measured at three time periods: preovulatory (PO) 48h after PMSG; midovulatory (MO) 4-7h after hCG; late ovulatory (LO) 9-12h after hCG. The offset of the nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME), the alpha(1)-adrenoceptor agonist phenylephrine and the beta-adrenoceptor agonist isoprenaline were tested. RESULTS: phenylephrine given i.v. increased the systemic blood pressure, and significantly decreased the IFP in the LO phase (78% of pre-treatment value). Local administration of phenylephrine or isoprenaline (1ml of 1.5-15 microM) by superfusion over the ovary did not change the IFP. Local administration of L-NAME (1ml of 2 microM) significantly lowered (P<0.05) the IFP in the MO and LO phases, but was without effect in the PO phase. CONCLUSION: this study reveals that IFP regulation may be related to changes of the systemic blood pressure and that NO may be one local ovarian mediator in IFP regulation.

Novel method for intrafollicular pressure measurements in the rat ovary: increased intrafollicular pressure after hCG stimulation.

The ovulatory process in the rat comprises a period of about 12-15 h, from the time of the preovulatory LH surge to follicular rupture and extrusion of the oocyte. Follicular rupture is most likely caused, at least in part, by decreased tensile strength at the follicular apex due to degradation of collagen fibres of the extracellular matrix. It has been debated whether changes in intrafollicular pressure occur during the ovulatory process and whether such changes facilitate rupture of the follicle. In the present study, rats were primed with equine chorionic gonadotrophin (eCG, 10 iu) followed by hCG (10 iu) 48 h later. The intrafollicular pressure in the preovulatory follicle was recorded during 1 h at distinct time phases of the ovulatory process by use of an active servo-null pressure system based on the proportionality between electrical resistance and pressure within the tip of an inserted micropipette. The basal intrafollicular pressure was 16.6 +/- 1.0 mm Hg at the preovulatory phase (48 h after eCG) and increased gradually throughout the ovulatory process to 21.4 +/- 2.4 mm Hg at 4-7 h after hCG (mid-ovulatory phase) and 23.9 +/- 1.9 mm Hg at 8-12 h after hCG (late ovulatory phase; significantly higher (P < 0.01) than the preovulatory phase). Short-term peaks of increased pressure, possibly representing contractility, were not detected in follicles of the preovulatory phase, but were seen in most follicles of the mid- and late ovulatory phases. The mean amplitude of the short-term pressure increases was 12.3 +/- 3.2 mm Hg and the increases occurred at intervals of 24.7 +/- 3.6 s. These short-term increments in intrafollicular pressure were still present after hysterectomy had been performed. The wall tension index was calculated by measuring the follicular size and estimating the thickness of the follicle wall. The index increased from 93.9 +/- 13.3 at the preovulatory phase to 207.3 +/- 47.7 (mid-ovulatory phase) and to significantly higher values at the late ovulatory phase (320.9 +/- 33.5). In conclusion, this study shows that there is an increase in intrafollicular pressure in the ovulating follicle of the rat ovary during the late stages of the ovulatory process, and that short-term increases in intrafollicular pressure occur during the late phase of the ovulatory process. These changes in pressure may be essential for follicular rupture to proceed normally.

The measurement of endometrial perfusion in norplant users: a pilot study.

The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to vascular fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.

Aquaporin-1 expression in visceral smooth muscle cells of female rat reproductive tract.

The aquaporins (AQ-s) are a group of intrinsic membrane proteins which facilitate movement of water across cell membranes; their recent identification in the kidney has led to the reappraisal of the mechanisms and pathways of water movement across epithelia. Aquaporin-1, (CHIP-28) is reported distributed in cardiac myocytes and vascular smooth muscle cells of large arteries. A related protein, AQ-4, has been identified in the sarcolemma of skeletal muscle fibres. We report aquaporin expression in the cell membrane of smooth muscle cells of the rat genital tract; fluorescence immunohistochemistry of rat uterine (fallopian) tube and vagina demonstrated AQ-1 in visceral smooth muscle of these tissues. In the uterine tube, AQ-1 labelling is most pronounced in the innermost longitudinal and the inner cells of the circular muscle layer and is absent from the outer longitudinal muscle layer of the myosalpinx. The possibility of a specific role for AQ-1 in tubal transport by altering the tubal luminal diameter during the estrus cycle is suggested.

The immunohistochemical response of the rat periodontal ligament endothelium to an inflammatory stimulus.

Recently, inflammation has been recognised as an important co-requisite to orthodontic tooth movement. When such a reaction is initiated, the process of up-regulation of certain adhesion molecules may occur, resulting in the extravasation of leukocytes. This may stimulate progenitor/precursor pathways and signals that regulate the biological responses resulting in tooth movement. We propose that up-regulation of leukocyte adhesion molecules occurs in response to orthodontic forces, resulting in circulating monocyte attraction, extravasation and differentiation into osteoclasts, which are responsible for bone resorption that results in orthodontic tooth movement. To investigate this hypothesis, it is necessary to determine whether periodontal ligament (PDL) endothelium responds to inflammatory stimuli as other organs do. We studied the normal distribution of endothelial adhesion molecule ICAM-1 within PDL vessels, and then the following exposure to an inflammatory endotoxin. The rat PDL blood vessels expressed ICAM-1 in response to the inflammatory stimulus, similar to other organs, suggesting that the inflammatory responses are similar. Whether and where in the PDL microvascular bed orthodontic forces cause up-regulation of ICAM-1 needs to be established.

Human endometrial perfusion after tubal occlusion.

We examined variations in human endometrial microvascular perfusion across one menstrual cycle in women who had undergone tubal ligation and did not report unusual menstruation. Endometrial red blood cell flux was monitored by laser Doppler fluxmetry via a fibreoptic probe atraumatically inserted transvaginally into the uterus of each of 13 conscious volunteers. The observations obtained have been compared with those previously reported from a matched control group of women [B.J. Gannon et al., Hum. Reprod., 12, 132-139 (1997)]. Women who had undergone tubal occlusion for sterilization exhibited greater endometrial perfusion during menstruation (cycle days 0-5), at the time of ovulation (cycle days 13-16) and in the late secretory phase (cycle days 23-28) than occurred in controls. In addition, vasomotion in the study group was lower than that in controls in the early and late secretory phase (cycle days 17-22 and 23-28). Tubal occlusion appeared to alter endometrial perfusion. It is possible that the reported menstrual changes in women following tubal ligation are a consequence of altered endometrial perfusion; a possible causative relationship is discussed.

PIP: Tubal ligation has been associated with an increase in postsurgical dysmenorrhea or menorrhagia. The present study used laser Doppler fluximetry to measure endometrial perfusion in 13 South Australian women who had undergone tubal ligation an average of 5.7 years earlier and did not report subsequent menstrual dysfunction. This technique provides a measure of the flux of red blood cells through a small sphere of tissue immediately adjacent to a probe placed over the endometrium. Measurements were taken once a week over 4 weeks (usually 1 menstrual cycle) and were compared with those obtained earlier by the authors from a matched control group of 19 women. Women who had undergone tubal occlusion exhibited greater endometrial perfusion than controls during menstruation (cycle days 0-5), at the time of ovulation (cycle days 13-16), and in the late secretory phase (cycle days 23-28). In addition, vasomotion was lower in the study group than among controls in the early (cycle days 17-22) and late (cycle days 23-28) secretory phase. Further exploration of the potential pathophysiology associated with tubal sterilization is warranted.

Endometrial perfusion across the normal human menstrual cycle assessed by laser Doppler fluxmetry.

This study investigated variations in microvascular perfusion of human endometrium across the menstrual cycle, using a laser Doppler technique to assess red blood cell (RBC) flux. Endometrial RBC flux was monitored by laser Doppler fluxmetry via a fibre optic probe inserted transvaginally into the uteri of 19 conscious normal volunteer women, on four occasions at weekly intervals over one menstrual cycle. Regional variation in RBC flux was investigated in 16 surgical patients under general anaesthesia and in five excised uteri. Endometrial perfusion exhibited short-term temporal variations consistent with the cardiac cycle and often also showed vasomotion (5-12 cycles/min). Mean endometrial perfusion differed between phases of the menstrual cycle in conscious women, being highest during early proliferative and early follicular phases. There were no significant regional differences in local mean endometrial perfusion in anaesthetized patients. No evidence of endometrial ischaemia/reperfusion episodes was found in any subject using this technique. This study provides benchmark data of variations in RBC flux per unit volume of tissue in the luminal approximately 1 mm of endometrium, across the normal human menstrual cycle. Flux values were highest at times associated with endometrial growth and preparation for implantation, indicating that RBC flux may be a useful parameter for assessment of endometrial physiology.

The effects of radiation on the contractile activity of guinea pig mesenteric lymphatics.

In order to assess the effects of irradiation on lymphatic function, the contraction frequency and maximum and minimum diameters of guinea pig mesenteric collecting lymphatic vessels were measured in vivo 4 hours after 1000 rads of abdominal irradiation. The mean contraction frequency for lymphatics from irradiated guinea pigs (7.6 +/- 0.7) was significantly higher than for normals (non-irradiated) (4.7 +/- 0.7) during an initial control observation period, but there was no difference in maximum or minimum diameter between the two groups during this period. Topical application of 10(-4) M noradrenaline (NA) significantly increased contraction frequency in both groups; lymph vessel diameter significantly decreased after NA in irradiated, but not in normal guinea pigs. Intravenous infusion of calcium dobesilate (200 mg/kg) caused a significant increase in the contraction frequency of lymphatic vessels in both normal (to 9.4 +/- 1.5) and irradiated (to 9.8 +/- 1.2) animals, but diameter was not significantly altered. Thus, lymphatic vessels from irradiated guinea pigs were still responsive to exogenous stimuli 4 hours post-irradiation and were initially pumping more actively than those from normal guinea pigs, presumably in response to radiation-induced edema. They also exhibited a supersensitivity to the vasoconstrictive effects of NA, perhaps due to an alteration of the pacemaker or smooth muscle cells by irradiation.

Effect of carbon monoxide intoxication on skin perfusion in anaesthetized rats.

Carbon monoxide intoxication decreases systemic blood pressure and peripheral resistance. In order to assess the role of the skin in this process, we measured the perfusion of hind limb shaven skin in anaesthetized rats during acute moderate carbon monoxide intoxication. At a steady blood level of 25% carboxyhaemoglobin, the red blood cell flux was measured as an index of tissue perfusion, using laser Doppler fluxmetry. The mean blood pressure decreased by 30% during carbon monoxide exposure, but there was no change in mean red blood cell flux of the hind limb skin microvessel bed. Thus, rat hind limb skin perfusion was not affected by acute moderate steady state carbon monoxide intoxication.