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S Ashraf

Publications and source records attributed to S Ashraf.

At least 19 recordsLinked to original sources
PubMed2006

Detection of antibodies against serotypes 1 and 2 infectious bursal disease virus by commercial ELISA kits.

Two distinct serotypes of infectious bursal disease virus (IBDV) are recognized in chicken and turkey flocks in the United States. Serologic testing of chicken flocks for serotype 1 viruses is routinely performed to monitor disease status and vaccination. Earlier studies indicated that enzyme-linked immunosorbent assay (ELISA) test detects antibodies to both serotypes of the virus, while the virus neutralization (VN) test is serotype specific. It is useful to evaluate currently available commercial ELISA kits for their ability to differentiate between antibodies elicited by the two serotypes. Three trials were performed in which chickens were orally inoculated with either a high or a low dose of serotype 1 STC or serotype 2 OH strains of IBDV. Sera collected at 0, 7, 14, and 21 days from these chickens and antisera procured from naturally infected broiler (n=20) and layer (n=30) flocks were tested with five different commercial ELISA kits and by VN. All ELISA kits detected different levels of antibodies elicited against serotype 1 of the virus and moderate and high levels of antibodies against serotype 2 virus. A correlation existed between the ELISA and the VN titers of experimentally infected chickens. All serum samples tested from the commercial layer flocks and 65% of the broiler flocks had antibodies against the OH strain. However, no correlation between the VN titers and ELISA titers was observed for the commercial broilers and layers sera by the majority of the kits. The results indicated that currently available commercial ELISA kits detect antibodies elicited by the two serotypes of IBDV. Hence, the prevalence of serotype 2 antibodies in the flocks should be considered while determining antibody profiles of the flocks against serotype 1 viruses.

Animals↗
PubMed2005

Interference between mild and pathogenic strains of infectious bursal disease virus in chickens.

Infectious bursal disease virus is a contagious, immunosuppressive disease of young chickens that is controlled by vaccination. Cross-protection occurs between different strains of the virus as a result of shared neutralizing epitopes. However, interactions between two antigenically similar strains (a mild and a pathogenic) coinfecting the same host have not been investigated. Groups of specific-pathogen-free chickens were inoculated with a mild strain followed by a pathogenic strain at 0, 16, 24, or 48 hr postinoculation (PI) with a mild strain. Virus persistence and the predominant strain of the virus were determined by reverse transcriptase-polymerase chain reaction and restriction fragment length polymorphism analysis, respectively, in bursas at 2, 4, 8, 14, and 21 days PI with the pathogenic strain. Severity of infection was assessed by the bursa/body weight ratios and histopathologic lesion scores. The mild virus interfered with replication of the pathogenic virus. The greatest interference was observed when the pathogenic strain was inoculated 24 hr PI with the mild strain. The interference phenomenon observed might be due to competition for host receptor sites or production of cytokine(s). This interference phenomenon could have practical implications for vaccine usage and protection.

Animals↗
PubMed2000

Neonatal sepsis: an etiological study.

OBJECTIVE: A periodic review of neonatal sepsis to asses any change in the infecting organism. METHOD: A prospective study was conducted at HMC and ASH, Karachi. The babies suspected to have or developed sepsis any time during hospitalization were investigated to establish the diagnosis and isolate the causative organism. Blood culture was taken at the time of admission or when sepsis was suspected. RESULTS: Out of 109 episodes of blood culture proven sepsis 68 presented as early onset (within 48 hours of birth) and 41 as late onset sepsis (after 48 hours of birth). In early onset group Gram -ve and Gram +ve organisms were almost equal, i.e. 33 and 35 respectively. Among the gram -ve organism most of the cases were due to Klebsiella sp, and Enterococcus was the commonest Gram +ve organism. In late onset group majority of infections were due to gram +ve organisms, i.e. 30 out of 41. Staph. aureus and Staph. epidermidis were commonest. The organisms were least sensitive to Ampicillin (< 20%) and highly sensitive to Amikacin (90% to 100%), Cefotaxime was also seen as a good choice of antibiotic with sensitivity of (84%-89%). CONCLUSION: Gram +ve organisms were the main cause of neonatal sepsis. Klebsiella sp. is still the commonest organism causing early onset sepsis. The data must be periodically reviewed and antibiotic policy revised accordingly.

Female↗
PubMed1999

Cytokine and S100B levels in paediatric patients undergoing corrective cardiac surgery with or without total circulatory arrest.

OBJECTIVES: Neurological damage following cardiopulmonary bypass (CPB) is difficult to objectively evaluate in infants. In adults, serum elevations of astroglial S100B correlate with proven brain injury independent of operative temperature. The deleterious effects of inflammatory cytokines, generated during CPB, on the brain have not been studied in infants using S100B as a marker for cerebral injury. METHODS: Twelve neonates, weighing 3.3 +/- 0.2 kg (total circulatory arrest group (TCA)) and 12 infants weighing 7.0 +/- 1.0 kg (cardiopulmonary bypass group (CPB)) underwent corrective cardiac surgery for various pathologies. Serial blood samples on induction, at the end of CPB, 30 min, 2 h and 24 h after the administration of protamine, were taken. The resultant plasma was frozen to -80 degrees C and stored for batch analysis. Cytokines were measured using ELISAs and S100B using a luminometric assay. RESULTS: The TCA group were younger and experienced a longer perfusion time than the CPB group (137 +/- 8 vs. 113 +/- 7, P = 0.04). The mean TCA time was 23 +/- 4 min. The TCA group had significantly higher levels of IL-6 (P = 0.001), IL-8 (P = 0.005) and S100B (P = 0.002) at 24 h. C5b-9 levels were significantly lower in the TCA group: end of CPB (P = 0.001), 30 min (P < 0.001), 2 h (P = 0.002). There was a weak, but significant correlation between IL-6 levels at the end of CPB and S100B levels 2 h later (r = 0.55, P = 0.03). Long extubation times were associated with high 24-h S100B levels (r = 0.52, P = 0.01). CONCLUSIONS: (1) The TCA group have prolonged rises of IL-6, IL-8 and S100B. (2) The TCA group generates significantly lower complement. (3) Astroglial injury, seen after surgery, may, in part, be cytokine mediated.

Antibodies, Monoclonal↗
PubMed1999

Cytokine gene polymorphisms predict acute graft rejection following renal transplantation.

BACKGROUND: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of acute rejection, while animal models suggest a role for interleukin-10 (IL-10) in promoting graft survival. It has also been shown that polymorphisms in the TNFA gene promoter (position -308) and in the IL-10 gene promoter (position -1082) correlate with differential production of these cytokines in vitro. The aim of this study was to determine whether TNF-alpha and IL-10 gene polymorphisms influence the incidence and severity of acute rejection in the first six months following renal transplantation. METHODS: The cytokine genotypes of 115 consecutive first cadaveric kidney allograft recipients and their donors were screened. The rejection episodes (REs) were defined clinically and confirmed histologically where possible and further classified according to severity (RS), namely steroid-resistant or responsive REs. The genotypes were then correlated with the REs and RS. RESULTS: The recipient TNF-alpha high producer genotype and IL-10 high producer genotype were significantly associated with multiple REs (>/=2) in human leukocyte antigen (HLA)-DR mismatched transplants (P = 0.0047 and P = 0.045, respectively), whereas only the TNF-alpha high producer genotype was associated with steroid-resistant REs (P = 0.025). When recipient cytokines were analyzed together, the TNF-alpha high/IL-10 high producer genotype had the worst prognosis, whereas TNF-alpha low/IL-10 low producer genotype was protective. CONCLUSIONS: We conclude that recipient TNF-alpha and IL-10 gene polymorphisms are determinants of REs and RS following kidney transplantation. Routine screening of these gene polymorphisms may have a clinical role in identifying patients at risk of multiple REs and severe rejections.

Cadaver↗
PubMed1999

Banff criteria as predictors of outcome following acute renal allograft rejection.

BACKGROUND: The Banff classification of renal allograft rejection grades acute tubulointerstitial rejection (AIR) by severity of tubulitis and acute vascular rejection (AVR) by severity of arteritis. The intensity of tubulitis has not, however, been demonstrated to be of prognostic value and other features such as glomerulitis and eosinophil infiltration are of uncertain significance. This study was performed in order to determine the clinical value of this pathological classification. METHODS: Banff criteria were correlated with outcome in 134 consecutive graft recipients transplanted in our unit over a 3-year period (1994 1996) who experienced at least one biopsy-confirmed acute rejection episode. Of 197 biopsies performed for the diagnosis of rejection, 177 contained at least one artery and were suitable for Banff grading. Tissue eosinophil counts were available for 101 biopsies. Clinical severity of rejection was classified as mild (fully responsive to pulse steroid therapy), moderate (partially steroid responsive) and severe (steroid unresponsive/requiring ATG therapy). RESULTS: Graft failure ensued in 18 of 58 patients with AVR compared with 10 of 65 patients with AIR (P= < 0.05). Clinical severity of rejection correlated with the presence of arteritis, but not severity of tubulitis; rejections graded I, IIA and IIB according to the Banff' 93 classification were clinically severe in 3/68 (4%), 2/28 (7%) and 15/67 (22%) respectively (P= <0.05). The presence of glomerulitis showed no correlation with clinical severity or graft loss. Tissue eosinophilia (>10 eosinophils/mm2) was present in 18 of 33 patients who had at least one episode of AVR (v1/2), compared with 11 of 45 patients who suffered only AIR (P= <0.02). CONCLUSIONS: We conclude that: arteritis, but not severe tubulitis or glomerulitis, is an adverse prognostic factor in acute rejection and that tissue eosinophilia is associated with vascular rejection. Our findings support the 1997 revision of the Banff classification, replacing grades with types of acute rejection.

Acute Disease↗
PubMed1998

Clinical response and temporal patterns of acute cellular rejection: relationship to chronic transplant nephropathy.

The association between acute cellular rejection (ACR) and the development of chronic rejection has been the subject of much debate. Studies have suggested that the two phenomena may be linked, or, conversely that there may be no association at all. In order to clarify this relationship the outcome of 284 renal allografts were examined. The transplants were all performed at a single institution between April 1989 and December 1991, allowing a minimum follow up of 5 years. ACR was classified into three clinical response groups: (1) fully responsive to therapy (type 1 ACR), (2) partially responsive (type 2) and (3) ACR requiring treatment with ATG or OKT3 (type 3). Acute and chronic rejection were determined by histological (Banff) criteria. Chronic transplant nephropathy (CTN) occurred significantly more frequently in those with late ACR after day 60 than in those who had early rejection (53.5% versus 17.3%, respectively, P < 0.00001). Acute rejection that was fully responsive to therapy (type 1) had no association with CTN, but partially responsive rejection and rejection requiring second-line treatment were both significantly associated with CTN (P < 0.0001 and P < 0.001, respectively). This study suggests that it is the clinical behaviour and response to treatment of ACR that is paramount in determining the onset of chronic rejection, and not hte mere presence or absence of the clinical phenomenon.

Acute Disease↗
PubMed1998

Inflammatory mediators in adults undergoing cardiopulmonary bypass: comparison of centrifugal and roller pumps.

BACKGROUND: The nonocclusive centrifugal pump is used for cardiopulmonary bypass (CPB) and mechanical cardiac assistance. This study examined its impact on proinflammatory cytokine release. METHODS: Forty-one patients undergoing elective coronary artery bypass grafting were randomized prospectively to either a standard roller pump group (n = 21) or a centrifugal vortex pump group (n = 20) for CPB. The two groups were well matched in age, sex, severity of disease, and duration of CPB and aortic cross-clamping. Plasma levels of the cytokines tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8, as well as terminal complement, neutrophil counts, and leukocyte elastase, were analyzed before, during, and after CPB. RESULTS: In both groups, traces of tumor necrosis factor-alpha were observed infrequently and interleukin-1beta was not detected. Plasma levels of interleukin-6 and interleukin-8 increased during and after CPB, reaching a peak at 2 hours after protamine administration in both groups before returning toward baseline at 24 hours. The release of interleukin-6 was significantly greater in the centrifugal group (p < 0.05), whereas the interleukin-8 concentration did not differ between the groups throughout the study period. Levels of terminal complement increased in both groups perioperatively, reaching a peak 30 minutes after protamine administration, whereas neutrophil counts and elastase peaked 2 hours after protamine administration. Plasma terminal complement, neutrophil counts, and elastase release were significantly higher in the centrifugal group (p < 0.05). Peak terminal complement correlated (r = 0.64, p < 0.01) with peak elastase in the centrifugal group only. CONCLUSIONS: This study confirms the proinflammatory nature of CPB in adults and demonstrates that use of the centrifugal pump induces a greater systemic inflammatory response than use of the standard roller pump.

Adult↗
PubMed1998

Serum S100beta release after coronary artery bypass grafting: roller versus centrifugal pump.

BACKGROUND: Microemboli generated during cardiopulmonary bypass (CPB) are implicated in the cerebral injury seen after coronary artery bypass grafting. Centrifugal pumps generate fewer microemboli than roller pumps. Increased S100beta levels have been reported after coronary artery bypass grafting, with levels greater than 1 ng/mL resulting in poorer neuropsychologic outcome. This study investigated the potential neurologic benefits of centrifugal pumps, by using S100beta as a marker for cerebral injury. METHODS: Thirty-two patients who had coronary artery bypass grafting were randomly assigned to two groups. Serial blood samples (preoperative, end of bypass, 30 minutes, and 2 and 24 hours after cardiopulmonary bypass) were taken and the serum analyzed for S100beta using a new immunoluminometric assay. RESULTS: Both groups were matched for age, number of grafts, and cardiopulmonary bypass and cross-clamp times. Postoperative serum S100beta levels were significantly higher in both groups than preoperative levels. Peak S100beta levels did not correlate with cardiopulmonary bypass time; however, 24-hour S100beta levels correlated with intubation time r = 0.40, p = 0.04). Th ere was no significant difference in S100beta levels between the groups at any of the time points. CONCLUSIONS: S100beta levels increased after coronary artery bypass grafting. Centrifugal pumps do not significantly decrease S100beta release. Persistently increased S100beta levels are associated with longer intubation times.

Calcium-Binding Proteins↗
PubMed1998

Cushing's syndrome caused by an adrenal adenoma.

A 10-year-old boy presented with features of Cushing's syndrome. Investigations, including ultrasound scan and computed tomography scans, demonstrated a right adrenal tumor. The tumor was excised and histologically found to be an encapsulated adrenal adenoma. Surgical excision is the treatment of choice for adrenal tumors. However, because it is often difficult to differentiate benign from malignant lesions on histopathologic grounds, these patients need a regular long-term follow-up.

Adrenal Cortex Neoplasms↗
PubMed1997

"Low-dose" aprotinin modifies hemostasis but not proinflammatory cytokine release.

BACKGROUND: Cytokines are implicated in the pathogenesis of the "whole-body inflammatory response" that may complicate the period after cardiopulmonary bypass (CPB). Low-Dose aprotinin in the pump during CPB has been shown to improve postoperative hemostasis and platelet preservation. We tested the hypothesis that low-dose aprotinin influences the inflammatory reaction (in terms of cytokine release) after CPB. METHODS: In a prospective, randomized study, 36 patients undergoing elective coronary artery bypass grafting were investigated. Nineteen patients received low-dose aprotinin (2 x 10(6) KIU (280 mg] in the pump), and a control group of 19 did not. Complement activation, cytokine production, leukocyte elastase release. D-dimer level, full blood count, postoperative blood loss, and transfusion requirements were analyzed before, during, and after after CPB. RESULTS: Interleukin-1 beta was not detected in either group, whereas traces of tumor necrosis factor-alpha were infrequently observed. Plasma elastase, interleukin-6, interleukin-8, and neutrophil count increased (p < 0.001) during and after CPB compared with the baseline levels, reaching a peak at 2 hours after protamine administration in both groups before returning toward baseline at 24 hours. Proinflammatory cytokine markers did not differ significantly (p > 0.1) between the groups throughout the study period. The C5b-9 level increased (p < 0.001) in both groups perioperatively, reaching its peak 15 minutes after protamine. Twenty-four-hour postoperative blood loss was significantly (p < 0.001) reduced in the aprotinin group in association with markedly reduced D-dimer levels (p < 0.001). Patients in the aprotinin group also received significantly less banked blood postoperatively than the control group (p < 0.01). CONCLUSIONS: Low-dose aprotinin fails to modify proinflammatory cytokine release, yet confers hemostatic improvement through reduced fibrinolysis in patients undergoing routine coronary artery bypass grafting.

Aged↗
PubMed1997

Low heparinization with heparin-bonded bypass circuits: is it a safe strategy?

BACKGROUND: The use of heparin-bonded cardiopulmonary bypass circuits with reduced doses of heparin sodium has been shown to give hemostatic benefits to the patient. However, fears persist that the use of less heparin may put the patient at risk for thrombotic events. This work tested the hypothesis that heparin-bonded circuits per se are effective in preserving cells and reducing thrombin generation when a reduced dose of heparin is used in vitro. METHODS: Simulated extracorporeal circulation was carried out using the same unit of fresh heparinized (1.1 U/mL) human blood to simultaneously perfuse a heparin-bonded circuit and a nonbonded circuit. Samples were taken at 30, 60, 120, and 360 minutes and analyzed for markers of cell activation and thrombin generation. RESULTS: The concentrations of platelet and white blood cell activation markers were found to be significantly lower in the heparin-bonded circuits compared with the nonbonded circuits. In addition, markers of thrombin generation were significantly lower in bonded circuits. Scanning electron microscopy revealed fewer adherent cells and less debris on the bonded surface compared with the nonbonded surface. CONCLUSIONS: Cell activation and thrombin generation were significantly reduced as a result of the presence of immobilized heparin in a system of cardiopulmonary bypass with reduced plasma heparin. However, evidence of contact activation in the bonded circuits was found after 120 minutes, indicating that anticoagulation in the system was not adequate. This becomes more important clinically where the extrinsic pathway of coagulation is also involved.

Anticoagulants↗
PubMed1997

Two-stage repair of adult coarctation of the aorta with congenital valvular lesions.

BACKGROUND: Coarctation of the aorta associated with intracardiac pathologic conditions presenting in adult life poses some technical and management challenges. When deciding on the best surgical strategy, the surgeon must pay careful attention to the changes that will occur in the circulation. METHODS: In our small series of 3 patients, the intracardiac pathologic lesions were corrected first, and the coarctation was repaired as a second-stage procedure 2 to 3 months later. RESULTS: All patients had an uneventful recovery from both operations. The potential problems of renal impairment caused by inadequate perfusion during bypass and perioperative systemic hypertensive complications resulting from coarctation of the aorta were not observed. At the time of coarctation repair as a second-stage procedure, anticoagulation was easily controlled. All 3 patients had short intensive care unit and hospital stays. CONCLUSIONS: Staged surgical repair of this complex pathologic combination in adult patients is a safe option and is easy to manage perioperatively.

Adult↗
PubMed1997

Release of proinflammatory cytokines during pediatric cardiopulmonary bypass: heparin-bonded versus nonbonded oxygenators.

BACKGROUND: Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients. METHODS: Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-alpha, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB. RESULTS: Significant levels of tumor necrosis factor-alpha were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01). CONCLUSIONS: The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry.

Cardiopulmonary Bypass↗
PubMed1997

Cell activation and thrombin generation in heparin bonded cardiopulmonary bypass circuits using a novel in vitro model.

OBJECTIVE: It is generally agreed that when the blood contact surfaces of a cardiopulmonary bypass circuit are treated with a layer of heparin molecules the activation of the humoral pathways is attenuated. However, there is still debate as to whether heparin-bonded circuits reduce thrombin generation. This study aims to examine the effects of immobilized heparin on cell activation and thrombin generation in a novel, well controlled model of cardiopulmonary bypass. METHODS: The model used consisted of a heparin-bonded and a non-bonded cardiopulmonary bypass circuit perfused in tandem with the same unit of fresh heparinized (3.3 U/ml) human blood for a period of 6 h. Samples were taken for analysis from the bag just prior to perfusion and at 30, 60, 120 and 360 min of perfusion. Whole blood was used to analyse platelet and white blood cell count, haematocrit and activated coagulation time. Plasma samples were prepared for batch analysis of the cell activation markers p-selectin, elastase and interleukin-8, and the thrombin generation markers thrombin-antithrombin and prothrombin fragment F1 + 2. A sample of tubing was taken from each circuit at the end of the perfusion and prepared for visualization by scanning electron microscopy. RESULTS: Platelet counts were significantly reduced in the non-bonded circuits compared with the heparin-bonded circuits at 30 (22 versus 200 x 10(9)/L P < 0.01), 60 (26 versus 193 x 10(9)/L P < 0.01) and 120 min (28 versus 193 x 10(9)/L P < 0.01) as were white blood cell counts at 30(1.5 versus 2.7 x 10(9)/L P < 0.01), 60 (0.9 versus 2.4 x 10(9)/L P < 0.01), 120 (0.9 versus 1.8 x 10(9)/L P < 0.01) and 360 min (0.4 versus 0.9 x 10(9)/L P < 0.05). The concentration of p-selectin was found to be significantly higher in the non-bonded circuits than in the heparin-bonded circuits at 30 (37 versus 29 ng/ml P < 0.01), 60 (37 versus 28 ng/ml P < 0.01). 120 (42 versus 27 ng/ml P < 0.01) and at 360 min (72 versus 46 ng/ml P < 0.01). Elastase was elevated in the non-bonded circuits at 30 (570 versus 145 micrograms/l P < 0.01), 60 (646 versus 278 micrograms/l P < 0.01) and 120 min (613 versus 403 micrograms/l P < 0.05) and interleukin-8 at 120 (705 versus 520 pg/ml P < 0.05) and 360 min (11326 versus 9910 pg/ml P < 0.05). A similar picture was found for the thrombin generation markers. Thrombin-antithrombin complexes were raised in the non-bonded circuits compared with heparin-bonded circuits at 60 (24 versus 13 micrograms/l P < 0.05) and 120 min (46 versus 17 micrograms/l P < 0.05) as was prothrombin fragment F1 + 2 at 30 (1.1 versus 0.7 nmol/l P < 0.01), 60 (1.3 versus 0.7 nmol/l P < 0.01), 120 (1.8 versus 0.9 nmol/l P < 0.01) and 360 min (15.0 versus 13.6 nmol/l P < 0.05). Scanning electron microscopy revealed a greater amount of adherent material on the non-bonded surface relative to the heparin-bonded surface. CONCLUSIONS: In a cardiopulmonary bypass circuit perfused with human blood the activation of platelets and white blood cells has been seen to be significantly reduced in the presence of a heparin-bonded surface. Thrombin generation due to contact activation of the intrinsic coagulation pathway is also reduced.

Adult↗
PubMed1997

Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells.

Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.

Animals↗