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Biomedical subjects

C Svensson

Publications and source records attributed to C Svensson.

At least 19 recordsLinked to original sources
PubMed2006

Evaluating the efficacy of serum haptoglobin concentration as an indicator of respiratory-tract disease in dairy calves.

The serum concentration of haptoglobin (S-Hp) was measured in 833 group-housed dairy calves from nine herds in south-west Sweden once at 24-56 days of age to evaluate the potential of S-Hp as an indicator of clinical respiratory-tract disease (CRD). Presence of disease (treated and non-treated) was assessed clinically by farmers and by a project veterinarian visiting the farms every third week. The median S-Hp of healthy calves was 0.06g/L (80% central range: 0.04-0.23), of calves with diarrhoea within the 10 days before sampling 0.07g/L (80% central range: 0.04-0.63), and of calves with CRD within the 14 days before sampling 0.09g/L (80% central range: 0.04-0.69). Eight different cut-off values were used to define a positive S-Hp analysis result: >0.05, >0.06, >0.07, >0.08, >0.09, >0.10, >0.15 and >0.20g/L. A rectal temperature >39.5 degrees C was denoted as fever. A positive result of five different diagnostic tests for CRD was defined as: (1) a positive S-Hp with fever absent, (2) a positive S-Hp with fever present, (3) either a positive S-Hp or fever, (4) both a positive S-Hp and fever, and (5) fever (regardless of S-Hp). The sensitivity (Se) and specificity (Sp) of each test were calculated from regression coefficients of generalized linear mixed models of the binary test results, applying a logit link. Apart from CRD status (within the 14 days before sampling; no or yes), the models included sex (bull or heifer), and for the test based on S-Hp alone, also rectal temperature (fever, no or yes). Confidence intervals (CI) of Se and Sp were estimated by simulation. Based on Se, Sp, and areas under Receiver Operating Characteristics curves, test 3 was considered the best. At optimal performance, giving equal importance to type I and II errors, i.e. at a S-Hp cut-off of 0.15g/L in heifer calves, Se was 0.64 (95% CI 0.50-0.77) and Sp 0.71 (95% CI 0.60-0.80), and at a S-Hp cut-off of 0.08g/L in bulls, Se was 0.52 (95% CI 0.40-0.64) and Sp 0.80 (95% CI 0.74-0.85). The other tests were judged as unsatisfactory indicators of CRD. In heifers, the proportion of CRD-positive calves in the herd was strongly associated with the proportion of test positives (S-Hp or fever; S-HP and fever), suggesting potential as a herd-level indicator.

Animals↗
PubMed2006

Morbidity in 3-7-month-old dairy calves in south-western Sweden, and risk factors for diarrhoea and respiratory disease.

The health status of 2947 heifer calves born in 1998 and raised in 122 Swedish dairy herds was monitored from birth to 210 days of age. Disease occurrence was recorded by farmers and by veterinarians who visited the farms six times yearly, examined the calves clinically and auscultated their lungs. The incidence risks of diarrhoea, ringworm and clinical respiratory-tract disease (CRTD) in calves from 3 to 7 months of age were 2.7%, 5.6% and 5.7%, respectively. The herd-level incidence risks of the three diseases were zero in 63.1%, 76.2% and 48.4%, respectively, of the herds. In positive herds incidence risks were 2.2-46.4%, 2.6-47.0% and 2.2-53.3%, respectively. The associations between the potential risk factors age at first grazing, air quality, birth place, feeding of colostrum, hygiene, number of animals, age range within the pen or building, pen area, pen location, previous housing type, present housing type, previous disease and season, and each of three binary outcome variables (diarrhoea, increased respiratory sounds and CRTD) were evaluated using two-level (calf; herd) variance component logistic models. Predictors significantly associated (P<0.05) with diarrhoea were pen area, season and the interaction between pen location and previous CRTD. Previous CRTD, season and heart girth at weaning were significantly associated with moderately to severely increased respiratory sounds. Predictors significantly associated with CRTD were previous diarrhoea, previous housing and season. It was concluded that the incidence of diarrhoea and CRTD in 91-210-day-old Swedish dairy calves is higher than previously reported from dairy herds in Sweden and the USA, and that diarrhoea, increased respiratory sounds and CRTD are associated with season, a history of disease during the first 90 days of age and, to some extent, housing factors.

Animals↗
PubMed2006

Effects of housing, management, and health of dairy heifers on first-lactation udder health in southwest Sweden.

Data on health, management, and housing from birth to first calving were collected for 2,126 heifers on semi-monthly visits made by project veterinarians to 107 dairy herds from southwest Sweden. Additional data were obtained from the official milk- and health-recording program. Factors associated with incidence of veterinarian-treated clinical mastitis (VTCM) in the period 7 d before (d -7) to 30 d after first calving and of elevated cow composite somatic cell count (SCC, > or =200,000 cells/mL) at first test milking after first calving, respectively, were investigated using a 2-level (animal and herd) logistic regression analysis after initial screening by univariate analyses. The incidence risk of VTCM during the complete first lactation (305 d) was 10.8%. Ten percent of the diseased animals had more than 1 case of VTCM and 51% of total cases occurred from -7 to 30 d postcalving. The incidence rate of VTCM during the complete first 305-d lactation was 1.13 cases per 100 cow-mo. In total, 18.1% of the animals had elevated SCC at first test milking (mean 21 d) after calving. Veterinarian-treated clinical mastitis at -7 to 30 d postcalving was associated with higher overall incidence of mastitis in the herd and with reproductive disorders (i.e., retained placenta, endometritis, pyometra, dystocia, or twin birth). The risk of elevated SCC increased with increasing percentage of cows in the herd that, some time during the year, had had an increased udder disease score (chronically increased SCC). Other factors associated with increased risk of elevated SCC were increasing amounts of concentrates fed to 11- to 16-mo-old heifers, moving to confined housing the day of calving instead of earlier, and use of restraint measures at milking. In addition, growth rate from birth to weaning, and several feed-related variables (e.g., amount of concentrates and type of roughage given) were associated with VTCM at -7 to 30 d post-calving or elevated SCC at first test milking in the univariate analyses.

Animals↗
PubMed2006

Mortality in Swedish dairy calves and replacement heifers.

The mortality of 8,964 heifer calves born in 122 dairy herds in southwest Sweden in 1998 to 2000 was monitored from January 1998 until December 2000. Farmers were requested to send carcasses for necropsy from animals that died from 1 d of age to first calving. Age and seasonal patterns of mortality were investigated using Kaplan-Meier curves. The median herd-level mortality risk was 2.1%. In total, 3.1% of the animals died before 90 d of age, 0.9% between d 91 and 210, and 2.2% between d 211 and first calving or d 810 (27 mo of age). The median age at death was 50 d and the risk of dying was highest during the first week of life. Of the 421 dead animals, 236 (56%) were subjected to either postmortem examination or were diagnosed as having died from trauma based on information from the farmers. In total, pneumonia was the most common cause of death (27%). However, in calves less than 31 d old, enteritis was the most common cause of death; in young stock 211 to 450 d old, trauma dominated; and in young stock more than 450 d old, trauma and calving-related diseases accounted for a majority of the mortality. The largest proportion of deaths was observed from January to March, and in June. Kaplan-Meier curves suggested that housing in small-group pens was associated with the lowest mortality (other housing systems were single pens and large-group pens with automatic milk feeders), but the association was not significant.

Age Factors↗
PubMed2005

The effect of group size on health and growth rate of Swedish dairy calves housed in pens with automatic milk-feeders.

Group pens equipped with automatic milk-feeding systems are increasingly being used for young dairy calves in Sweden. The system is, however, associated with an increased risk of clinical respiratory-tract disease and a reduced growth rate. In an experimental study we compared the health and growth rate of two different group sizes of calves (6-9 versus 12-18) kept in pens with automatic milk-feeders. The experiment was performed from September 2002 to February 2004, in nine commercial dairy farms in south-west Sweden. Each farm was equipped with two pens with automatic milk-feeders and no possibility of direct contact between calves from different pens. The calves were housed individually until 3-35 (median, 12) days of age, and then were allocated to one of the two group pens by random-number lists. Altogether 892 calves were studied: 297 in the small- and 595 in the large-sized groups. The calves' heart girths were measured at birth and at 56 days of age. Blood samples for analysis of serum haptoglobin concentration (S-Hp) were collected once for each calf, at four to eight weeks of age. Diseases were recorded by the farmers and by a veterinarian, who visited the farms every third week and physically examined all the calves. The effects of group size on the risks of diarrhoea, clinical respiratory-tract disease and increased respiratory sounds, and on the growth rate and S-Hp were evaluated using multiple logistic- and linear-regression models with herd as fixed effect. Age at transfer to group pen, breed, immunoglobulin concentration of colostrum received, parity of the dam and presence of diarrhoea before transfer to the group pen, season, sex, year, and, in the analysis of growth rate, birth heart girth were extra explanatory variables. Calves in pens for 12-18 calves had a higher incidence of respiratory illness (OR: 1.4) and grew 0.022 cm/day less than calves housed in groups of 6-9 animals (equivalent to approximately 40 g/day). We detected no differences between calves kept in the small-sized versus the large-sized groups in terms of risk of diarrhoea or mean S-Hp. We concluded that housing calves in groups of under 10 calves is preferable from a health and growth perspective.

Animal Husbandry↗
PubMed2005

Dynamics of virus infections involved in the bovine respiratory disease complex in Swedish dairy herds.

The dynamics of bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus 3 (PIV-3), bovine corona virus (BCoV) and bovine viral diarrhoea virus (BVDV) infections were studied in 118 dairy herds in south western Sweden. By using serology on paired samples from three approximately 7 vs. approximately 15-month-old calves per herd, the propagation of infections was investigated over about a 1-year period. The results implied that at least 74% of calves had experienced one or more of the monitored infections at the age of approximately 7 months (Sample 1, Spring); 30%, 48%, 34% and 8% were seropositive to BRSV, PIV-3, BCoV and BVDV, respectively. Seroconversions to BRSV, PIV-3, BCoV and BVDV occurred in 26%, 38%, 50% and 3% of seronegative animals and 63% had antibodies against two or more infections at approximately 15 months (Sample 2). In total, 90-97% of animals that were seropositive in Sample 1 remained positive in Sample 2. A significant association was found between BVDV and BCoV (P = 0.01). Moreover, a significantly higher proportion of herds in which no calves had a recorded history of respiratory disease (n = 15) were classified as negative to all four infections monitored when compared to herds in which disease was observed (P = 0.0002). This study showed a high infection burden in young animals and effective spread of BRSV, PIV-3 and BCoV in one area of Sweden. BVDV infections were restricted to a few herds, reflecting the effect of a voluntary control program against BVDV in Sweden.

Animal Husbandry↗
PubMed2004

Use of antimicrobial drugs in Swedish dairy calves and replacement heifers.

A total of 3081 heifer calves in 122 Swedish dairy herds were monitored from birth to first calving, and all their diseases and treatments were recorded. There were 1268 cases of infectious diseases, of which 335 (26.4 per cent) were treated with antimicrobial drugs. Just over 90 per cent of the treatments were given during the first 210 days of the calves' lives, but only 61.8 per cent of the total quantity of antimicrobial drugs was consumed during this period. The most common diseases from birth until 210 days were respiratory diseases and diarrhoea; treatments for mastitis and interdigital phlegmon (foul in the foot) were more common after 420 days of age. Slightly more than 60 per cent of the treatments were given by the farmers without prior consultation with a veterinary surgeon.

Animals↗
PubMed2003

Influence of heavy traffic, city dwelling and socio-economic status on nasal symptoms assessed in a postal population survey.

BACKGROUND: The association between social position, living environment and nasal symptoms is inconsistent. We wanted to test how living environment, occupation and social position were associated with nasal symptoms. METHODS: In a postal survey study of a random sample of 12,079 adults, aged 20-59 years living in the southern part of Sweden the relationship between nasal symptoms, socio-economic status and environmental factors was analysed. RESULTS: The response rate was 70% (n = 8469) of whom 33% reported significant nasal symptoms. Nasal discharge, thick yellow discharge, a blocked nose, sneezing and itching were strongly associated with living close to heavy traffic or living in cities. Most of the nasal symptoms provoked by extrinsic factors were more frequently reported among subjects who lived close to heavy traffic and in cities. Apart from thick yellow discharge and nasal symptoms provoked by damp/cold air which were more common in the socio-economic position "low" no relation to the socio-economic group was found. The prevalence of self-reported hay fever was neither affected by site of living nor by socio-economic status. Nasal symptoms evoked by "allergic" factors were linked to asthma but symptoms evoked by non-allergic factors were linked to chronic bronchitis/emphysema CBE. CONCLUSIONS: To conclude, we found a strong relation between geographical site and the prevalence of self-reported nasal symptoms which emphasizes the environment as a risk factor for nasal symptoms. Only by merging the socio-economic groups into "low" and "middle/high" an association to nasal symptoms was apparent. Nasal symptoms evoked by "allergic" factors were linked to asthma but symptoms evoked by "non allergic factors" were linked to CBE.

Adult↗
PubMed2003

Diving beetles (Dytiscidae) as predators of mosquito larvae (Culicidae) in field experiments and in laboratory tests of prey preference.

Field experiments were performed in artificial ponds to evaluate how the density of predatory diving beetles (Dytiscidae) would affect the population levels of mosquito larvae (Culicidae). Mosquitoes colonizing the ponds were predominantly species of the genus Culex. In 2000, most of the dytiscids colonizing the ponds were small (Hydroporus spp.), and these predators had no impact on the size of larval mosquito populations, not even in ponds with added dytiscids. In 2001, larger beetles (Ilybius, Rhantus, and Agabus spp.) were more common, and there were significantly fewer mosquito larvae in ponds with the highest numbers of dytiscids. There was a negative correlation between numbers of diving beetles in the ponds and the mean body length of mosquito larvae. In neither year could dytiscid densities be maintained above a certain level owing to emigration. In laboratory tests, there were marked differences between three common dytiscid species in regard to preferences for Daphnia and Culex species as prey: Colymbetes paykulli Erichson chose mosquito larvae more often, whereas both Ilybius ater (De Geer) and I. fuliginosus (Fabricius) preferred Daphnia spp. All of the tested dytiscids consumed large numbers of prey. Since some dytiscid species can efficiently decrease populations of mosquito larvae, they are probably important in the natural control of these dipterans.

Animals↗
PubMed2003

Cryptosporidium parvum and Giardia intestinalis in calf diarrhoea in Sweden.

The objective of this study conducted in 75 herds was to investigate the presence and significance of Criptosporidium parvum and Giardia intestinalis in Swedish dairy calves in comparison with rotavirus, coronavirus and Escherichia coli K99+. The farmers were asked to collect faecal samples from each heifer calf that had diarrhoea between birth and 90 days of age, and also from a healthy calf of the same age. In total, 270 samples were collected and analysed. C. parvum, either alone or together with G. intestinalis and/or rotavirus, was detected in 16 (11%) and 6 (5%) of the samples from diarrhoeic and healthy calves, respectively. Even though a higher proportion of diarrhoeic calves shed C. parvum, the difference between the groups was not statistically significant (p = 0.067), possibly due to the low number of positive samples. G. intestinalis was found in 42 (29%) of the diarrhoea samples and in 29 (23%) of the samples from healthy calves. Rotavirus and coronavirus were demonstrated in 24% and 3% of the diarrhoea samples, respectively, whereas E. coli K99+ was only found in samples from 2 healthy calves. C. parvum and G. intestinalis were found in samples from calves 7 to 84 days of age and during all seasons. The results confirm that C. parvum is present in Swedish dairy herds and might have clinical significance. G. intestinalis was the most common agent found but the importance of this parasite remains unclear. Both parasites have suggested zoonotic potential and thus warrant further attention. In addition, rotavirus is a major pathogen in neonatal enteritis in Sweden, whereas coronavirus and E. coli K99+ seem to be of less importance.

Animals↗
PubMed2002

Randomized trial of Lichtenstein versus Shouldice hernia repair in general surgical practice.

BACKGROUND: The aim of the present randomized trial was to compare the Shouldice procedure and the Lichtenstein hernia repair with respect to recurrence rate, technical difficulty, convalescence and chronic pain. A further aim was to determine to what extent general surgeons in routine surgical practice were able to reproduce the excellent results reported from specialist hernia centres. METHODS: Three hundred patients with primary inguinal hernia were randomized to either a Shouldice repair or to a tension-free Lichtenstein repair. In a pretrial training programme the five participating general surgeons were taught to perform the two techniques in a standard manner. Follow-up was performed after 8 weeks, 1 year and 3 years. The last examination was performed by an independent blinded assessor. RESULTS: There was a significant difference in operating time in favour of the Lichtenstein technique. After a follow-up of 36-77 months seven recurrences were found in the Shouldice group (95 per cent confidence interval (c.i.) 1.3 to 8.1) and one in the mesh group (95 per cent c.i. 0.0 to 2.0). Chronic groin pain was reported by 4.2 and 5.6 per cent in the Shouldice and Lichtenstein groups respectively. It was characterized as mild or moderate in all except two patients who had the Shouldice operation. CONCLUSION: Lichtenstein hernia repair was easier to learn, took less time and resulted in fewer recurrences. It was possible to achieve excellent results with this technique in a general surgical unit.

Adult↗
PubMed2002

Salvage abdominoperineal resection in anal epidermoid cancer.

BACKGROUND: In the management of isolated locoregional failure after (chemo)radiation therapy for anal epidermoid cancer, salvage abdominoperineal resection (APR) is the treatment of choice. The results of a 15-year consecutive population-based series are reviewed. METHODS: Details of all patients with anal epidermoid cancer treated from 1985 to 2000 in the Stockholm Health Care Region were recorded prospectively. Among 308 patients with biopsy-proven anal epidermoid cancer, there have been 39 isolated locoregional failures after sphincter-preserving therapy. Thirty-five patients have undergone salvage APR. The medical records of these 35 patients were reviewed retrospectively with regard to surgical and oncological results. RESULTS: There were no postoperative deaths. There was considerable morbidity related to the perineal wound, with postoperative perineal infections in 13 patients and delayed healing beyond 3 months in 23 patients. Complications unrelated to the perineal wound were found in 13 patients. The crude 5-year survival rate for the 35 patients was 52 per cent (median follow-up 33 months). Patients with persistent disease fared significantly worse than those with locoregional recurrence (crude 5-year survival rate 33 versus 82 per cent; P < 0.05, log rank test). CONCLUSION: Salvage APR in anal epidermoid cancer is associated with a high complication rate but may result in long-term survival.

Adult↗
PubMed2002

Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis.

BACKGROUND: Cutaneous microdialysis in vivo in human skin is demonstrably of use in the study of skin metabolism, percutaneous absorption and skin inflammation. A promising area for cutaneous microdialysis is the measurement of cytokines. This requires catheters equipped with membranes permeable to molecules of high molecular weight. OBJECTIVES: To address technical problems of poor sample volume retrieval and analysis sensitivity in the simplest model of provocation, namely the insertion of the catheter itself in vivo into human dermis. METHODS: Use of a polyethylenesulphone membrane, with a cut-off value of 100,000 Da, allowed measurement of target molecules of large molecular weight. Using an adaptation of a commercially available high sensitivity enzyme-linked immunosorbent assay, the ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal skin of six healthy volunteers after insertion of the microdialysis catheter. RESULTS: Reliable sample volumes and high analyte recovery were achieved either by push-pull pumping or by standard pumping using a perfusate consisting of Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during the first 100 min after catheter insertion. The IL-6 concentration then increased and remained elevated for the duration of the experiments. CONCLUSIONS: Technical and analytical modifications in the microdialysis technique have allowed the measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine production is the result of the dermal trauma caused by catheter insertion, but the cellular source of the IL-6 is at present unknown.

Adult↗
PubMed2001

From V8Ga36.9Zn4.1 and Cr8Ga29.8Zn11.2 to Mn8Ga27.4Zn13.6: a remarkable onset of Zn-cluster formation in an intermetallic framework.

The series of isotypic compounds V8Ga41 --> V8Ga36.9Zn4.1 --> Cr8Ga29.5Zn11.2 --> Mn8Ga27.4Zn13.6 with the V8Ga41 structure type (space group R3, Z = 3) was prepared and structurally characterised by X-ray diffraction experiments (V8Ga41: a 13.9351(5), 14.8828(12); V8Ga36.9Zn4.1: a = 13.9244(7), c = 14.8660(9): Cr8Ga29.8Zn11.2: 13.7153(5), c = 14.6872(9); Mn8Ga27.4Zn13.6: a = 13.6033(6), c = 14.6058(16)). The site occupancies of the ternary compounds were refined from neutron powder-diffraction data and exposed a startling segregation of Zn and Ga, which finally resulted in the formation of separated Zn13 cluster entities-corresponding to almost ideal centred cuboctahedra or small pieces of fcc metal-in the Mn compound, which has the highest Zn content in the series. The homogeneity ranges of the underlying phases T8Ga41 xZnx were determined to be 0 < x < 4.1(3), 8.7(3) < x < 11.2(3) and 13.6(4) < x < 16.5(3) for T = V, Cr and Mn, respectively. The different ranges of composition of the phases reflect the requirement of an optimum electron concentration for a stable V8Ga41-type structure, which is in the narrow range between 159 and 165 electrons per formula unit. First-principles electronic-structure calculations could explain this fact by the occurrence of a pseudo gap in the density of states at which the Fermi level is put for this particular electron concentration. Furthermore the nature of the Zn/Ga segregation was revealed: T-Zn interactions were found to be considerably weaker than those for T-Ga. This places the Zn atoms as far as possible from the T atoms, thus leading to the formation of cuboctahedral Zn13 entities.

Journal Article↗
PubMed2001

Superconductivity in single crystals of the fullerene C70.

The observation of superconductivity in doped C60 has attracted much attention, as these materials represent an entirely new class of superconductors. A maximum transition temperature (Tc) of 40 K has been reported for electron-doped C60 crystals, while a Tc of 52 K has been seen in hole-doped crystals; only the copper oxide superconductors have higher transition temperatures. The results for C60 raise the intriguing questions of whether conventional electron-phonon coupling alone can produce such high transition temperatures, and whether even higher transition temperatures might be observed in other fullerenes. There have, however, been no confirmed reports of superconductivity in other fullerenes, though it has recently been observed in carbon nanotubes. Here we report the observation of superconductivity in single crystals of electric-field-doped C70. The maximum transition temperature of about 7 K is achieved when the sample is doped to approximately four electrons per C70 molecule, which corresponds to a half-filled conduction band. We anticipate superconductivity in smaller fullerenes at temperatures even higher than in C60 if the right charge density can be induced.

Journal Article↗
PubMed2001

Functional knockout of the corepressor CtBP by the second exon of adenovirus E1a relieves repression of transcription.

The C-terminal binding protein (CtBP) acts as a transcriptional corepressor upon recruitment to transcriptional regulators. In contrast, interaction between CtBP and the adenovirus E1A protein is required for efficient activation of E1A-responsive genes, suggesting that E1A might block CtBP-mediated repression. Recruitment of CtBP to a promoter, either as a Gal4CtBP fusion or through an interaction with a Gal4 fusion protein expressing the CtBP interacting domain (CID) of E1A, resulted in transcriptional repression. The second exon of E1A, containing the CID, alleviated repression by Gal4E1ACID-recruited CtBP, but not Gal4CtBP-mediated repression, suggesting that E1A prevented repression by blocking promoter recruitment of CtBP. E1ACID was also sufficient to derepress transcription from several cotransfected promoter constructs. Furthermore, inducible expression of E1ACID in established cell lines resulted in significant changes of endogenous gene expression, possibly by sequestration of CtBP. Together, these data indicated that CtBP might act as a wide-range regulator of transcription. Although CtBP was shown to interact with histone deacetylases (HDACs), transcriptional repression by a Gal4CtBP fusion protein was not sensitive to inhibition of HDACs by trichostatin A (TSA). In contrast, TSA eliminated E1ACID derepression of E1A second exon-responsive promoters. Although the reason for this difference remains to be experimentally verified, it is possible that the requirement for HDACs might differ depending on the mechanism by which CtBP becomes promoter recruited.

Adenovirus E1A Proteins↗
PubMed2001

The acute antihyperalgesic action of nonsteroidal, anti-inflammatory drugs and release of spinal prostaglandin E2 is mediated by the inhibition of constitutive spinal cyclooxygenase-2 (COX-2) but not COX-1.

Western blots show the constitutive expression of COX-1 and COX-2 in the rat spinal dorsal and ventral horns and in the dorsal root ganglia. Using selective inhibitors of cyclooxygenase (COX) isozymes, we show that in rats with chronic indwelling intrathecal catheters the acute thermal hyperalgesia evoked by the spinal delivery of substance P (SP; 20 nmol) or NMDA (2 nmol) and the thermal hyperalgesia induced by the injection of carrageenan into the paw are suppressed by intrathecal and systemic COX-2 inhibitors. The intrathecal effects are dose-dependent and stereospecific. In contrast, a COX-1 inhibitor given systemically, but not spinally, reduced carrageenan-evoked thermal hyperalgesia but had no effect by any route with spinal SP hyperalgesia. Using intrathecal loop dialysis catheters, we showed that intrathecal SP would enhance the release of prostaglandin E(2) (PGE(2)). This intrathecally evoked release of spinal PGE(2) was diminished by systemic delivery of nonspecific COX and COX-2-selective inhibitors, but not a COX-1-selective inhibitor. Given at systemic doses that block SP- and carrageenan-evoked hyperalgesia, COX-2, but not COX-1, inhibitors reduced spinal SP-evoked PGE(2) release. Thus, constitutive spinal COX-2, but not COX-1, is an important contributor to the acute antihyperalgesic effects of spinal as well as systemic COX-2 inhibitors.

Administration, Oral↗