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Biomedical subjects

B Esposito

Publications and source records attributed to B Esposito.

At least 37 records · Page 2Linked to original sources

Role of NO in flow-induced remodeling of the rabbit common carotid artery.

Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91 +/- 2 in control versus 98 +/- 3 mm Hg in L-NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animals (106.1 +/- 10.7 versus 196.2 +/- 32.3 mL/min, P < .003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15 +/- 0.12 and 2.54 +/- 0.1 mm, respectively, P < .02), but the increase was less in the L-NAME-treated than the control group (3.24 +/- 0.09 and 4.64 +/- 0.17 mm, respectively, P < .0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME-treated animals than in controls (4.14 +/- 0.29 versus 7.94 +/- 0.51 mm, P < .0001). As a result of artery enlargement, WSS was normalized in the flow-loaded left CCA of the control group (8.87 +/- 0.77 dynes/cm2) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7 +/- 2.2 dynes/cm2, P < .006). Moreover, a highly significant positive correlation between WSS and blood flow was obtained in L-NAME-treated animals (r = .84, P < .0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME-treated group (0.75 +/- 0.09 versus 0.49 +/- 0.04 mm2 and 4504 +/- 722 versus 2717 +/- 282 cells/mm2, P < .03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.

Administration, Oral↗

Pentoxifylline selectivity inhibits tumor necrosis factor synthesis in the arterial wall.

Pentoxifylline (PTX) has been reported to potentially inhibit tumor necrosis factor (TNF) synthesis by monocytes/macrophages. Because inflammatory processes involve both leukocytes and vascular cells, we tested the effects of PTX on TNF and interleukin-6 (IL-6) production by the vessel wall in response to lipopolysaccharide (LPS). Rings of rat thoracic aorta were incubated for 24 h in DMEM containing antibiotics and 1% fetal calf serum in the presence of 1 microgram/ml LPS. TNF and IL-6 were biologically assayed using L-M fibroblast cytotoxicity and B9 hybridoma cell proliferation, respectively. Maximal LPS-induced production of TNF and IL-6 by the aorta was 0.77 +/- 0.04 and 23.3 +/- 3.5 x 10(3) U/mg dry weight, respectively. The addition of PTX dose-dependently suppressed the production of TNF by 26 +/- 7%, 58 +/- 6%, and 85 +/- 9% at 10, 100, and 1,000 microM, respectively. This effect was selective for TNF, because the production of IL-6 was not affected by any dose of PTX, suggesting a selective gene regulation of TNF and IL-6 in vascular cells. These results may have clinical implications. PTX may be useful in vascular inflammatory diseases, in which serum TNF levels have been shown to be correlated with the severity of the disease.

Animals↗

Increased production of tumor necrosis factor and interleukin-6 by arterial wall of aged rats.

Plasma cytokine levels are enhanced in aged animals and in elderly people. Vascular cells are known to be both targets and sources of cytokines. To investigate the effect of aging on vascular cytokine synthesis, we studied tumor necrosis factor (TNF), interleukin-6 (IL-6), and prostacyclin (PGI2) production by the arterial wall using organoid culture of aorta from 10- (n = 8) and 30-mo-old (n = 8) rats, after activation by lipopolysaccharide (LPS). Biological activity of TNF and IL-6 was measured in supernatant from incubated vessels. 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of PGI2, a secondary inflammatory mediator, was measured using enzyme immunoassay. In the absence of LPS, TNF production was undetectable in most animals and was not significantly increased in the aged group. By contrast IL-6 and 6-keto-PGF1 alpha productions, in the absence of LPS, were significantly greater in 30- (8,140 +/- 1,350 U/micrograms DNA and 23.2 +/- 6.4 ng/micrograms DNA, respectively) than in 10-mo animals (3,060 +/- 350 U/micrograms DNA and 8.4 +/- 1.6 ng/micrograms DNA, P < 0.01 and P < 0.05, respectively). LPS-induced production of TNF, IL-6, and 6-keto-PGF1 alpha was significantly increased in old rats, being increased respectively by 3.2-, 3.5-, and 2.4-fold at 1 ng/ml LPS, compared with the production in young rats. Because TNF and IL-6 are capable of regulating vascular cell function such as proliferation protein synthesis and contractility, these cytokines might play a major role in age-related remodeling of arteries and age-related vascular diseases.

6-Ketoprostaglandin F1 alpha↗

[Fecal incontinence and rectal prolapse. Clinico-functional assessment].

Rectal Prolapse is a rare and distressing condition, with a multifactorial etiopathogenesis. Often, this pathology is associated with fecal incontinence. The recommended approach to the patient with rectal prolapse and fecal incontinence is to repair the prolapse first, then deal particularly with fecal incontinence at a second operation. A retrospective, clinical and manometric study has varying degrees of fecal incontinence. Clinically five of their operation, and a further three patients improved, in two patients the degree of fecal incontinence remained invariable. One patient was worsened after surgery. Manometrically resting and pressure (RAP) was significantly higher in continent patients than in voluntary contraction pressure (MVCP) (p < 0.05) in preoperative testing. Postoperatively, there was a significant increase in the resting anal pressure as well as in maximum voluntary contraction pressure. Patients who remained incontinent had a significantly lower RAP and MVCP than patients who improved our regained continence. In conclusion this study shows an alteration of internal and external sphincteric function in patients with rectal prolapse. The surgical treatment of this disease improves sphincteric function. Incontinent patients with RAP < 10 mmHg and MCVP < 20 mmHg, probably they would be better treated simultaneously either for rectal prolapsus and incontinence. In this kind of patients the perianal proctectomy with total sphincteroplasty could be the elective treatment.

Aged↗

Elevated temperature accelerates and amplifies the induction of nitric oxide synthesis in rat macrophages.

Evidence has accrued that nitric oxide (NO) is an effector molecule in cell-mediated immunity, and it is generally agreed that fever is beneficial to host defence. Therefore, the role of elevated temperature in the induction of NO synthesis was examined in rat peritoneal macrophages activated by lipopolysaccharide (LPS). When macrophages were incubated in vitro at 40 degrees C, the time between macrophage activation and the induction of NO synthesis, as assessed by nitrite accumulation in the medium, was shortened as compared with incubation at 37 degrees C, and nitrite accumulation was markedly enhanced by 2.6- and 1.8-fold after 6 and 9 h of LPS activation, respectively. These results suggest that elevated temperature may contribute to enhance host defence by accelerating and amplifying the induction of NO synthesis in macrophages.

Animals↗

Facial trauma in motor vehicle accidents: etiological factors.

The effects of seat belts and the use of alcohol and drugs have been studied as etiological factors in facial trauma to occupants of motor vehicle accidents (MVAs). During a 15-month period, 461 patients were admitted to a regional trauma center as a result of injuries sustained in MVAs. Two hundred thirty-seven (51%) of these patients had facial trauma. Facial trauma was the single most common injury in these patients. One hundred eighty-five patients (78%) had major soft tissue injury, and 52 patients (22%) had facial bone fractures. Forty-two of 237 patients (18%) with facial trauma were wearing seat belts compared with 74 of 224 patients (33%) without facial trauma who were wearing seat belts at the time of the accident. Large numbers of patients who were wearing seat belts at the time of the accident had minor injuries and were never admitted to the hospital. Sixty-five of 224 patients (24%) without facial trauma and 121 of 237 patients (51%) with facial trauma tested positive for alcohol or drugs. The majority of the patients who tested positive for alcohol had blood alcohol levels of more than 100 mg/dL. Head injuries and blunt chest trauma were most commonly associated injuries in these patients. This study suggests that use of alcohol and drugs in occupants of the motor vehicle had a major effect on the etiology of facial trauma. Also it supports the data that suggests that the use of seat belts prevents a wide range of injuries including facial trauma in MVAs.

Accidents, Traffic↗

Albumin transport characteristics of rat aorta in early phase of hypertension.

The effects of early-stage hypertension on the macromolecular transport characteristics of the aorta have been investigated in rats 1 week after the ligature of the abdominal aorta between the two renal arteries. The animals were left untreated or treated for 1 week with an angiotensin converting enzyme inhibitor (enalapril, 6 mg/kg per day). Blood pressure of a subgroup of hypertensive rats was acutely lowered to a normal level by injection of enalaprilat (1.5 mg/kg) at the time of the experiment. 131I-Albumin and 125I-albumin were injected 90 minutes and 5 minutes, respectively, before the rats were killed. The transmural distribution of the relative tissue concentrations across the wall was obtained using a serial frozen-section technique. Short-term albumin uptake permitted calculation of apparent endothelial permeability coefficients, and 90-minute uptake was used to estimate the steady-state albumin distribution within the media. The effect of early-stage hypertension on the characteristics of the arterial macromolecular transport depended on the aortic site; the ascending aortic arch appeared not to be affected. In the thoracic and abdominal aorta, the endothelial permeability coefficients increased significantly in hypertensive rats. This increase was not a direct effect of the arterial pressure, since the values were not significantly different when the pressure was acutely normalized. The 90-minute albumin concentration in the media was enhanced in hypertensive rats and returned to the normal value by acutely lowering the blood pressure, indicating that the increase observed in hypertensive rats resulted from a direct effect of pressure, possibly increased pressure-driven convection and/or pressure-induced stretching of the wall. Treatment by angiotensin converting enzyme inhibitor prevented hypertension and protected against its effects in hypertensive animals.

Albumins↗

Postoperative pain control by transdermal fentanyl. Preliminary comparison of two dosages to a fixed-interval i.m. morphine regimen.

The efficacy of postoperative pain control with two doses of transdermal fentanyl were compared to a fixed-interval intramuscular (i.m.) morphine regimen in 21 patients undergoing orthopedic surgical procedures. The two transdermal fentanyl patches with delivery rates of 70-80 micrograms/hr and 90-100 micrograms/hr, groups one and two, respectively, were compared to an i.m. morphine regimen of 150 micrograms/kg every 6h, group three. Transdermal patches were applied one hour prior to surgery and removed after 24h. Analgesia, safety scores, side effects, and a global postoperative evaluation were recorded by a blinded physician at frequent intervals up to 36h. No significant difference in pain intensity, evaluated by the visual analog scale, were found between the three groups. Group two had the lowest discomfort score. Groups one and two had a significantly lower respiratory rate than group three. Although there were isolated significant differences in peripheral hemoglobin saturations, these differences were not consistent. This is the first study in which transdermal fentanyl was compared to a fixed-interval i.m. morphine protocol without supplementation with other narcotics. The results show that fentanyl by a transdermal route can provide analgesia comparable to i.m. morphine. No clinically important adverse side effects were found in any of the study groups.

Administration, Cutaneous↗