Effect of inhibiting prostaglandin synthesis on edema formation and albumin leakage during thermal trauma in the rat

Prostaglandins (PGs) participate in the inflammatory response, but the contribution of endogenously synthesized PGs to edema formation and increased vascular permeability is not known. Using a 10% scald burn in the rat, we measured water content (as percent, wet minus dry/wet weight) and ¹³¹I-RISA leakage (counts/g dry tissue) in scalded and normal skin at 30 minutes and 3 hr post injury. Four groups (10 rats/group) in each time period studied: control; scald; scald, 5 mg/kg indomethacin; scald, 10 mg/kg indomethacin. Indomethacin was administered intravenously 30 minutes before the scald; RISA was injected intravenously 30 min before termination of the study. In all indomethacin-treated groups immunoreactive plasma PGA was significantly lower (p < 0.05) than in scalded, untreated groups. All scalded groups showed significantly higher RISA counts and water content than did the control group (p < 0.01). At 30 min post-injury the indomethacin-treated groups did not differ from the untreated scald group (p> 0.20). In the 3 hour study all scalded groups had significantly higher content and RISA counts than control (p < 0.01). Thus PGs produced during thermal trauma do not greatly contribute to the edema formation and increase in vascular permeability.     

A modified technique for permeability studies in the superfused hamster cheek pouch

We report here a modification of the superfused hamster cheek model for use in vascular permeability studies. Radio-iodine labeled serum albumin (I-125 RISA) is injected prior to the superfusion period. Plasma content is calculated on a μ1/100mg wet weight basis and compared to the contralateral (non-superfused) cheek pouch. Water content is calculated on a percentage basis and compared in the same manner. Results demonstrate that superfusion causes an increase in permeability of protein and water. Plasma content is reduced by catalase, indomethacin or FPL 55712 pretreatment, suggesting that free-radicals, prostaglandis and leukotrienes are released during superfusion. Water content increase is refractory to pretreatment. The advantages of this system and its application are discussed.     

The effect of alpha-melanocyte stimulating hormone on colonic inflammation in the rat

The effect of alpha-melanocyte stimulating hormone (alpha-MSH) on colonic inflammation in the rat. In this study, we investigated the effects of alpha-MSH administration on trinitrobenzene sulfonic acid-induced colitis and the role of nitric oxide and prostaglandins in this response. alpha-MSH treatment (25 microg/rat, intraperitoneally; twice daily for 3 days) reduced the colonic macroscopic lesions compared to untreated ones in both acute and chronic colitis groups. This effect was reversed by pretreatment with the nitric oxide donor, sodium NP (4 mg/kg, intravenously) or cyclooxygenase-1 selective antagonist indomethacin (5 mg/kg, subcutaneously) in the acute group and with the cyclooxygenase-2 selective antagonist nimesulide (3 mg/kg, subcutaneously) in the chronic group. alpha-MSH had no effect on colonic wet weight and myeloperoxidase activity compared to the untreated colitis group. However, protein oxidation was markedly elevated in the alpha-MSH-treated group compared to untreated ones. Nitroprusside and indomethacin reversed the effect of alpha-MSH on macroscopic lesions in the acute groups, whereas nimesulide showed a similar effect in the chronic group. In conclusion, the results of our study show a protective role of alpha-MSH on colonic lesions which partially involves nitric oxide and prostaglandins.     

烫伤大鼠早期口服谷氨酰胺对血浆氨基酸代谢的影响

研究烫伤早期口服谷氨酰胺 (GLN)后GLN及其相关氨基酸的代谢变化。以Wistar大鼠为烫伤模型 ,烫伤后早期口服GLN ,并以 83 5-50型氨基酸自动分析仪的生理体液法测定血浆游离氨基酸。结果烫伤后饲标准饲料(C)组血浆GLN在烫伤后 2d和 5d降低 ,与GLN代谢相关的丙氨酸和氨无显著性变化 ;GLN饲料 (G)组各时相点GLN均增加 ,1 0h和 8d增加显著 ,与GLN代谢相关的丙氨酸和血氨增加显著 ;GLN +精氨酸 (G +A)组GLN在 2d降低 ,血氨升高显著。与C组比 ,G和G +A组血浆总氨基酸、支琏氨基酸、GLN、丙氨酸、r-氨基丁酸和氨均较C组高。提示 ,烫伤后早期口服GLN能提高血GLN和与之代谢相关的氨基酸浓度。     

Effects of dexamethasone on the blood-brain distribution of albumin and alpha-aminoisobutyric acid in vasogenic cerebral edema

The effects of dexamethasone (Dex) on the blood-brain distribution of 14C-alpha-aminoisobutyric acid (AIB) and 125I-albumin (RISA) was studied in the rat freeze-lesion model of cerebral edema. Untreated and Dex-treated rats were studied by intravenously administering either AIB or RISA immediately after or one day after localized cortical freezing. The AIB experiments were terminated after 10 min; the RISA experiments were terminated after 30 min or 4 hr. Local tissue distribution of AIB and RISA was assessed by quantitative autoradiography. The distribution of both RISA and AIB within the lesion was unaffected by Dex. In the tissue around the lesion, Dex did not alter the distribution of AIB in the 10 min experiments or of RISA in the 30 min experiments. Dex did, however, diminish the movement of RISA into the adjacent tissue during the 4-hr experiments. The intralesional AIB and RISA distribution data plus the perilesional 10-min AIB and 30-min RISA distribution data indicate that Dex does not act by reducing the flow of solutes and water across damaged or leaky vessels in and around the lesion. The 4-hr RISA data suggests that Dex alters the structure of the extracellular space in the tissue around the lesion (especially in the white matter) and thereby increases the resistance of the interstitium to the flow of solutes and fluid from the lesion into the adjacent tissue.     

Oxytocin enhances the basal release of uterine prostaglandin F2 alpha, but not that of PGE1, or of PGE2, and changes the metabolism of exogenous arachidonate, favouring the formation of prostaglandin F2 alpha and 5-HETE. Relationships with its uterotonic action and modulation by estradiol

We attempted to explore possible mechanism(s) subserving the influence of oxytocin on uterine motility by studying the action of the hormone on: 1) the contractile activity of isolated rat uteri in the presence or absence of indomethacin; 2) the synthesis and release of prostaglandins (PGs) into the solution incubating the uterine tissue as well as the metabolism of labelled arachidonic acid; 3) the uptake of 45Ca2+ by uterine strips. The experiments were bone with uterine preparations isolated from spayed rats treated or not with 17-beta-estradiol. The values of isometric developed tension (IDT) and of frequency of contractions (FC) induced by oxytocin in uterine strips isolated from spayed and spayed-estrogenized rats, were not modified by indomethacin at 10(-6) M. On the other hand, uterine strips from untreated spayed rats, release into the incubating medium approximately equal amounts of PGE1, PGE2 and PGF2 alpha. The in vitro presence of oxytocin (50 mU/ml) increased significantly (p 0.05) the output of PGF 2 alpha without changing the release of PGE1 or PGE2. Uteri from spayed rats injected prior to sacrifice with 17-beta-estradiol released significantly less PGE1 and PGE2 (p less than 0.005) than preparations from non-injected animals, whereas the output of PGF2 alpha in the suspending solution remained unchanged. Following estrogenization the addition of oxytocin to preparations obtained from spayed-estrogenized rats also increased the output of uterine PGF2 alpha (p less than 0.001) without changing that of PGs E1 or E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Capillary permeability changes in the uteri of recipient rabbits after transfer of blastocysts from indomethacin-treated donors

Blastocysts recovered from control or indomethacin-treated (10 mg/kg s.c. twice daily starting on Day 4.5 of pregnancy) donor rabbits were transferred to the uteri of Day-6 or 6.5 pseudopregnant recipients. The minimal time required to cause an increase in capillary permeability in the endometrium underlying control blastocysts was approximately 9 h. Blastocysts derived from the indomethacin-treated donors were depleted of PGE and PGF (determined by RIA) and were unable to produce any increase in capillary permeability during the same time period, although after 46 h in vivo the diameters of the implantation swellings related to control or indomethacin-treated blastocysts were not different. This suggests that, in the untreated recipients, blastocysts depleted of PGs can become replenished and then release these PGs in a site-directed manner. Indomethacin thus causes a delay rather than a complete inhibition of implantation. Incubation of the indomethacin-treated blastocysts in vitro led to replenishment with PGs, but such replenished blastocysts failed to induce an increase in capillary permeability within the same time-frame as control blastocysts. Evidence is presented that indomethacin is probably not the cyclooxygenase inhibitor of choice, since it interferes with PG uptake and efflux. Such an action could explain the failure of the replenished blastocysts to induce a normal increase in capillary permeability.     

Effect of indomethacin, tiaprofenic acid and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2

Gastric ulcerogenicity and depletion of endogenous prostaglandins (PGs) content induced by tiaprofenic acid, dicrofenac and indomethacin were examined using the same antiinflammatory effective doses. Male Wistar rats were given each of these drugs intragastrically 24, 18, and 3 hrs before sacrifice in the following doses (mg/kg): indomethacin (0.8, 4 and 20); tiaprofenic acid (1.2, 6 and 30); dicrofenac (0.8, 4 and 20). Endogenous prostacyclin (PGI2) and PGE2 in fundic mucosa were determined by radioimmunoassay. The three compounds produced fundic mucosal lesions in a dose-dependent manner. However, tiaprofenic acid and dicrofenac were both less potent than indomethacin in producing gastric mucosal lesions at similar antiinflammatory doses. Mucosal PGE2 content was abolished by the three compounds in the following doses (mg/kg): indomethacin (4 and 20); tiaprofenic acid (6 and 30); dicrofenac (20). Mucosal PGI2 was maintained around 50% of the control value in rats given tiaprofenic acid in a dose of 6 mg/kg or dicrofenac in a dose of 4 mg/kg, while indomethacin in a dose of 4 mg/kg markedly reduced mucosal PGI2 to 17% of the control value. In larger doses, tiaprofenic acid and dicrofenac were also significantly less potent in reducing mucosal PGI2 than indomethacin. These results suggest that the difference in ulcerogenicity between indomethacin and the other two compounds was closely related to their potency in decreasing PGI2 in the gastric (fundic) mucosa.     

Effect of vasodilator prostaglandins on the vascular renin-angiotensin system

The interaction of prostaglandin (PG) with the vascular renin-angiotensin (R-A) system was examined by studies on the effects of PGI2, PGE2 and the inhibitor of PG synthesis, indomethacin, on the release of angiotensin II (Ang II) from isolated rat mesenteric arteries. The Ang II released from the vasculature was measured after its concentration in a Sep-Pak C18 cartridge connected to the perfusion system. After perfusion with drugs, the specific vascular renin activity inhibited by anti-renin antibody was determined. The basal perfusion pressure was constant (19.6 +/- 1.1 mmHg) at a flow rate of 4.5 ml/min, and was not changed by any of these drugs. The basal levels of Ang II release and vascular renin activity were 44 +/- 5 pg/30 min and 113 +/- 8 pg Ang I/mg protein/hr, respectively. Infusion of PGI2 (10(-6) M) significantly decreased both Ang II release (p less than 0.01) and vascular renin activity (p less than 0.05) as compared with the control levels. Infusion of PGE2 (10(-6) M) decreased Ang II release significantly (p less than 0.05) and vascular renin activity slightly. Infusion of indomethacin (10(-6)M) increased vascular renin activity significantly (p less than 0.01). Pretreatment with indomethacin (10 mg/kg, ip) for 2 days also increased vascular renin activity (p less than 0.01). These results indicate that in contrast to their effects on the renal R-A system, PGs suppress the vascular R-A system and that these two local vasoactive factors interact to regulate vascular tone.     

Intravenous beta agonist in severe acute asthma.

STUDY OBJECTIVE--To determine whether salbutamol is more effective in treating severe asthma when given intravenously or by inhalation. DESIGN--Randomised trial of short term response to intravenous versus nebulised salbutamol in acute severe asthma. SETTING--District general hospital (secondary care centre). PARTICIPANTS--76 patients aged 16-70 admitted to hospital with acute severe asthma (peak expiratory flow rate less than 50% of predicted) during study period. Five withdrawn because of adverse effects of treatment or non-response. Of remaining 71, 34 allocated to nebuliser group and 37 to intravenous treatment group. Patients with history of cardiovascular disease or recent corticosteroid or intravenous bronchodilator treatment excluded. Admission characteristics similar in the two groups. INTERVENTIONS--All patients given 5 mg nebulised salbutamol on admission before randomisation plus 200 mg hydrocortisone bolus intravenously and 35% inspired oxygen throughout. Nebuliser group received two more 5 mg doses of nebuliser salbutamol at 30 minutes and 2 hours; intravenous group received 4 hours'' continuous salbutamol infusion (12 micrograms/min) starting at 30 minutes plus supplementary intravenous potassium chloride. No other bronchodilators used. ENDPOINT--Change in peak expiratory flow rate over 4 hours. MEASUREMENTS and MAIN RESULTS--Peak expiratory flow rate improved more in intravenous group (25.2%) than in nebuliser group (14.3%) (p less than 0.01, 95% confidence interval 2.4 to 19.1%). Tachycardia caused two withdrawals from intravenous group; non-response caused three withdrawals from nebuliser group. CONCLUSIONS--Intravenous salbutamol is more effective than nebulised salbutamol in acute severe asthma but may have unacceptable cardiovascular effects.     

Indomethacin and gonadotrophin release from rat pituitaries.

The influence of low (5 mcM) and high (200 mcM) concentrations of indomethacin on gonadotropin release from rat pituitaries was studied in vitro. Low concentrations significantly (p less than .05) reduced the release of luteinizing hormone (LH) in comparison with controls, whereas high concentrations significantly (p less than .05) increased the rate of release. The release of follicle stimulating hormone (FSH) was not affected. When pituitary tissue was stimulated by LH-releasing hormone (LH-RH), the high concentration of indomethacin significantly (p less than .05) increased LH release and produced a nearly significant (p less than .01) increase in FSH. The low concentration was without effect. The effect of the addition of prostaglandins (PGs) alone and in combination with indomethacin was also investigated. PGE-1 significantly (p less than .05) increased the release of LH. However, there was no significant (p greater than .1) interaction between the 2 drugs. The effects on the release of FSH were similar. The addition of PGE-2 or PGF-2alpha slightly increased the release of LH and FSH (p greater than .1). It is suggested that high concentrations of indomethacin probably do not inhibit PG synthesis, but may inhibit cyclic nucleotide phosphodiesterase.     

Prophylactic intravesical instillation of epinephrine prevents cyclophosphamide-induced hemorrhagic cystitis in rats

The objective of this study is to investigate the potential protective effects of intravesical instillation of epinephrine in cyclophosphamide-induced hemorrhagic cystitis. In an earlier study, we have shown that epinephrine promotes hemostasis on established hemorrhagic cystitis induced by cyclophosphamide. Female Sprague-Dawley rats were divided into seven groups as follows: group 1: positive control (150 mg/kg, cyclophosphamide, i.p.), group 2: negative control (10 microg/ml, epinephrine, intravesical), co-administration of cyclophosphamide (150 mg/kg, i.p.), group 3: saline (intravesical), groups 4-6: epinephrine (2.5, 5, and 10 mu g/ml, intravesical), and group 7: mesna (50 mg/kg, i.p.). Rats were sacrificed on 3 consecutive days and the urinary bladders were removed, weighed, and evaluated. The vesical vascular permeability was determined by wet bladder weight and Evan's blue dye absorbance. After 24 hours of cyclophosphamide administration, severe hemorrhagic cystitis was induced with marked edema, hemorrhage, and inflammation. In the epinephrine-treated groups, symptoms of hemorrhagic cystitis (such as edema, inflammation, and hemorrhage) were reduced significantly. Intravesical instillation of epinephrine prevents edema, hemorrhage, and inflammation in rats with cyclophosphamide-induced hemorrhagic cystitis.     

Study of diet and drug interactions on prostanoid metabolism

To study the extent to which combinations of different dietary lipids stimulate or inhibit prostanoid synthesis groups of 12 rats were fed diets containing 10% (w/w) of either safflower oil, hydrogenated coconut oil/safflower oil, cod liver oil/safflower oil or cod liver oil/linseed oil for a period of four weeks. All diets, with the exception of the safflower oil feed, contained similar levels of linoleic acid. Two further groups of rats placed on the cod liver oil diets were injected with indomethacin (4 mg/kg, i.p.) every three days to establish the completeness of dietary prostaglandin (PG) inhibition. In spite of a 20 fold difference in dietary linoleic acid content, the safflower oil group had similar PG generating capacities to the saturated fat control group, suggesting tight metabolic control of PGs and their precursors. Although there were prostanoid variations in tissue responses, both of the cod liver oil diets substantially reduced generation of aortic, whole blood and renal prostanoids, and decreased urinary PG excretion. The degree of inhibition of renal PGs was substantially greater in the cod liver oil/linseed oil group, with prostaglandin levels being 35% lower than those observed in the cod liver oil/safflower oil fed animals suggesting that linolenic acid and the marine oil fatty acids act synergistically to inhibit formation of 2-series prostaglandins. Concurrent administration of omega-3 fatty acids and indomethacin reduced PG levels further than those obtainable by diet alone, demonstrating that the diets did not result in maximal inhibition. Awareness of these various effects is important for both physiological or clinical studies in which dietary manipulations are used as a means of modifying prostanoid synthesis.     

滚压泵在乳猪肺灌注模型建立中的应用

目的通过滚压泵建立一种操作简单的猪隔离肺持续灌注和缺血再灌注模型,并比较两种灌注方法对肺的损伤。方法12只乳猪随机分为缺血再灌注组（对照组）和持续灌注组（实验组）。分别在左、右心耳以及肺动脉插管。滚压泵将贮血器中的灌注液泵入肺动脉,灌注双肺后再通过左心耳将灌注液引流回贮血器,建立猪肺灌注模型。对照组双肺停止灌注90min后灌注30min,实验组双肺持续灌注120min,灌注流量均为80mL/kg.min。测定实验前后的肺静态顺应性以及灌注液中TNF-α、IL-6变化。测定肺组织湿干比并进行电镜观察。结果实验组肺静态顺应性（实验组6.14±1.17mL/cmH2O,对照组7.89±0.94mL/cmH2O,p=0.017）、湿干比（对照组5.18±0.97,实验组3.84±1.08,P=0.048）、TNF-α指标均优于对照组（实验组0.80±0.26ng/mL,对照组0.52±0.15ng/mL,P=0.044）（P〈0.05）,电镜下的肺损伤程度轻于对照组。结论通过滚压泵建立猪肺持续灌注和缺血再灌注模型具有操作简便的特点。持续性非搏动灌注较之缺血再灌注对肺的损伤更轻。     

Differential roles of p55 and p75 tumor necrosis factor receptors on stretch-induced pulmonary edema in mice

Ventilator-induced lung injury plays a crucial role in the outcome of patients with acute lung injury. Previous studies have shown a role for the cytokine tumor necrosis factor-alpha (TNF) in stretch-induced alveolar neutrophil recruitment, but the involvement of TNF in stretch-induced pulmonary edema is unclear. We investigated the effects of TNF through its individual p55 and p75 receptors on early pulmonary edema formation during high stretch ventilation, before neutrophil infiltration. Anesthetized wild-type or TNF receptor single/double knockout mice were ventilated with high tidal volume ( approximately 38 ml/kg) for 2 h or until they developed arterial hypotension. Pulmonary edema was assessed by physiological parameters including respiratory mechanics and blood gases, and by lavage fluid protein, lung wet:dry weight ratio, and lung permeability measurements using fluorescence-labeled albumin. High stretch ventilation in wild-type and TNF receptor double knockout animals induced similar pulmonary edema, and only 25-30% of mice completed the protocol. In contrast, the p55 receptor knockout mice were strongly protected from edema formation, with all animals completing the protocol. Myeloperoxidase assay indicated that this protective effect was not associated with decreased pulmonary neutrophil sequestration. The p75 receptor knockout mice, however, displayed increased susceptibility to edema formation, and no animals survived the full 2 h. These results demonstrate a novel role for TNF signaling (independent from its effects on neutrophil recruitment) specifically through the p55 receptor, in promoting high stretch-induced pulmonary edema, whereas p75 signaling may play an opposing role.     

Effect of indomethacin, tiaprofenic acid and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2

Gastric ulcerogenicity and depletion of endogenous prostaglandins (PGs) content induced by tiaprofenic acid, dicrofenac and indomethacin were examined using the same antiinflammatory effective doses. Male Wistar rats were given each of these drugs intragasrically 24, 18, and 3 hrs before sacrifice in the following doses (mg/kg): indomethacin (0.8, 4 and 20); tiaprofenic acid (1.2, 6 and 30); dicrofenac (0.8, 4 and 20). Endogenous prostacyclin (PGI₂) and PGE₂ in fundic mucosa were determined by radioimmunoassay. The three compounds produced fundic mucosal lesions in a dose-dependent manner. However, tiaprofenic acid and dicrofenac were both less potent than indomethacin in producing gastric mucosal lesions at similar antiinflammatory doses. Mucosal PGE₂ content was abolished by the three compounds in the following doses (mg/kg): indomethacin (4 and 20); tiaprofenic acid (6 and 30); dicrofenac (20). Mucosal PGI₂ was maintained around 50% of the control value in rats given tiaprofenic acid in a dose of 6 mg/kg or dicrofenac in a dose of 4 mg/kg, while indomethacin in a dose of 4 mg/kg markedly reduced mucosal PGI₂ to 17% of the control value. In larger doses, tiaprofenic acid and dicrofenac were also significantly less potent in reducing mucosal PGI₂ than idomethacin. These results suggest that the difference in ulcerogenicity between idomethacin and the other two compounds was closely related to their potency in decreasing PGI₂ in the gastric (fundic) mucosa.     

Mechanism for increase in tracheobronchial blood flow induced by hyperventilation of dry air in dogs

To test whether the consistent increase in tracheal and bronchial blood flow observed in dogs during hyperventilation of dry air might be the result of release of mediators such as vasodilatory prostaglandins or neuropeptides, we studied two groups of anesthetized mechanically ventilated dogs. Group 1 (n = 6) was hyperventilated for four 30-min periods with 1) warm humid air (38-40 degrees C, 100% relative humidity), 2) warm dry air (38-40 degrees C, 0% relative humidity), 3) warm humid air, and 4) warm dry air. After period 2, a loading dose of indomethacin (4 mg/kg iv) was given over 15 min followed by a constant infusion (4 mg.kg-1.h-1). Group 2 (n = 10) was hyperventilated for four 15- to 20-min periods by use of the protocol described above. After period 3 (group 2a) or period 2 (group 2b), topical 4% lidocaine hydrochloride solution was instilled into the trachea and main stem bronchi. Five minutes before the end of each period of hyperventilation, cardiac output and vascular pressures were measured. To determine airway blood flow, differently labeled radioactive microspheres were injected into the left atrium. After the last measurements, dogs were killed and the lungs excised. Blood flow to the trachea, main stem bronchi, and parenchyma (group 1 only) was calculated. Results showed that hyperventilation of dry air produced a significant increase in blood flow to the trachea and bronchi (period 2). In group 1, this increase was attenuated (P less than 0.02) after administration of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adipose-derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP-induced septic acute lung injury rats via sTNFR1

We hypothesized that the adipose-derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis-induced acute lung injury (ALI). A total of 120 male adult Sprague–Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP–ADMSCs, and CLP–sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 10⁶ ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5-Ethynyl-2′-deoxyuridine-labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin-10 (IL-10) were higher in the CLP–ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP–sTNFR1 siRNA groups than in SC group. Tumor necrosis factor-α and IL-6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL-6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.     

Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular Fx1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 +/- 198 mg/day compared to a level of 1180 +/- 306 seen in the untreated animals (p less than 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower does of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear.     

Retinopathy of prematurity (ROP) and indomethacin therapy in premature infants with paten ductus arterious (PDA)

Recent studies suggested that prostaglandins (PGs) may play a role in the pathogenesis of retinopathy of prematuriry (ROP). To evaluate if PGs inhibitor, indomethacin, would affect the incidence or severity of the ble-blind controlled study of indomethacin for the closure of PDA. Twenty-three were in the control group and 24 in the indometchin group. Indirect ophthalmospic examinations wee performed from about 4 weeks of postnatal age and onward and needed. There was no significant differences between the groups with respect to birth weight, gestational age, postnatal age, Apgar score, and cardiopulmonary status shortly after birth and at the time of study.Six in the control and 2 in the indomethacin group (p=0.58) developed active ROP; one in each group developed cicatricial ROP. It appears that with current doses of therapy, indomethacin does not increase the incidence or severity of ROP.