Biomedical subjects

J J Romero

Publications and source records attributed to J J Romero.

At least 19 recordsLinked to original sources

PubMed2005

Effect of neosporosis on productive and reproductive performance of dairy cattle in Costa Rica.

A cross-sectional study was conducted to assess the effect of neosporosis on productive and reproductive parameters in dairy cows. Cows (n=2743) from 94 farms located in the most important dairy areas in Costa Rica were used in the study. The size of the herds ranged from 32 to 379 females (mean=110, median=125). An indirect ELISA was used to determine the serostatus of the cows towards Neospora caninum. The effect of neosporosis on milk production was analysed by a mixed linear model. In addition, the effects on calving interval (days) and calving to conception interval (days) were analysed by survival analysis. The risk of abortion in relation to N. caninum serostatus was assessed by logistic regression, with herd as a random effect. Overall, 1185 of 2743 cows (43.3%) were seropositive for Neospora. Eighty-nine of 94 (94.7%) farms were classified as Neospora-seropositive. It was estimated that cows seronegative to Neospora produced an additional 84.7L of milk (P=0.6). Serostatus did not have a significant effect on the length of the calving interval in the Cox proportional hazard survival analysis (Hazard ratio=1.2, 95% CI: 0.9, 1.4). The logistic regression model had a weak positive association between serostatus and abortion (OR 1.7, 95% CI: 0.8, 3.9), but did not show a strong association between serostatus and the number of services per conception (OR=0.95, 95% CI: 0.7, 1.3). In conclusion, there were no significant effects of Neospora serostatus on production and reproductive performance in this study.

Animals↗

PubMed2004

Effect of a killed whole Neospora caninum tachyzoite vaccine on the crude abortion rate of Costa Rican dairy cows under field conditions.

A standard field trial was carried out to assess the effect of a commercial Neospora-vaccine based on whole killed tachyzoites (Bovilis-Neoguard, Intervet) on the abortion rate. Eight hundred and seventy-six cows, over 2.5 months pregnant, belonging to 25 Costa Rican dairy herds, were used in the analysis. For each cow vaccinated, a cow of the same herd, breed and age category, was selected as control. The period of administration of treatments extended from June to November of 2000. The treatments were administered in two, 5-ml doses 1 month apart, the first dose given between day 75 and 90 of gestation. The incidence of abortion among all treated cows was of 16.0% (140/876). The treatment specific incidence was 11.2% (49/438) and 20.8% (91/438) for the vaccinated and the placebo group, respectively. The prevented fraction by vaccination amounted to 0.46 (95% CI: 0.26, 0.61), and the cumulative incidence ratio for the vaccinated group was 0.54. The Cox hazard ratio was 0.51(95% CI: 0.37, 0.72), meaning that the force of abortion is reduced twice in the vaccinated group. The results of this study, the first one following this type of design, shows that the killed whole Neospora caninum tachyzoite preparation had a reasonable effect on the abortion rate in Costa Rican dairy cattle.

Abortion, Veterinary↗

PubMed2003

The effect of the dam-calf relationship on serostatus to Neospora caninum on 20 Costa Rican dairy farms.

An epidemiological study was conducted on 20 dairy herds previously diagnosed as seropositive for Neospora caninum. The number of females per farm varies from 41 to 296. All females present on the farms were bled once in the period of July and August 2000. A total of 3002 females were bled. An indirect ELISA was used to determine the serostatus of the animals. The analysis of the data was performed in four steps: (1) descriptive statistics about the serological status and general characteristics of the cattle; (2) calculation of vertical and horizontal transmission; (3) an univariate analysis and, (4) a multivariate logistic regression analysis with herd as random effect. The within-herd seroprevalence varied between 25.0% (34/136) and 70.5% (203/288). Seven hundred and forty-seven dam-daughter pairs were available, involving daughters of any age. Daughters in the specific age-class of 2- and 3-years old had a higher seroprevalence (P<0.01) compared with younger and older age-classes. The risk of being seropositive when being born to a mother that tested seropositive (prevalence ratio (PR)) was 2.8-fold increased which coincides with a 5.3-fold increased odds. The probability of horizontal infection amounts to 0.22. The probability of a seropositive offspring due to vertical transmission was 0.64 (attributable fraction among exposed (AFexp)). The multivariate logistic regression showed a significant 6.0-fold increased odds for being seropositive when born from a seropositive mother. Also the within-herd seroprevalence level was significantly associated with the serostatus of the daughters. In the specific conditions of the dairy herds involved in this study, the serostatus of the cows should be not used as a predictor of the serostatus of daughters due to the increased probability of horizontal transmission.

Age Distribution↗

PubMed2002

Factors associated with Neospora caninum serostatus in cattle of 20 specialised Costa Rican dairy herds.

Twenty-five specialised Costa Rican dairy farms (located in the Poás area) were used to determine neosporosis seroprevalence and the association of seropositivity with environmental and management factors. The farms involved were selected intentionally and all of them use VAMPP 5.1 (Veterinary Automated Management and Production Control Programme) as management-information system. Holstein-Friesian, Jersey and crosses between them were the most-frequent breeds in these herds. The number of females per farm varied from 41 to 296. Our cross-sectional study had two phases. In the first phase, we determined the presence or absence of seropositivity at herd level. For the second phase, all females in 20 seropositive farms were bled. Serum samples were tested for antibodies to Neospora caninum using an indirect enzyme-linked immunosorbent assay (ELISA). A questionnaire with factors mentioned in the literature was administered to the farmers. Logistic regression (LR with herd as random effect) was used to assess the relationships of the serostatus at the individual level with characteristics of the cows and environmental factors. In the first phase all herds had >20% seropositive females; therefore, all herds were eligible for the second phase. In the second phase, the overall prevalence was 39.7% (1191/3002), and within-herd prevalences were between 25.0 and 70.5%. Age 3-6 years, parity < or =2 of the dam of the cow, Jersey breed and lack of purposive sampling to diagnose abortive infectious disease were associated with positive serostatus; other management and environmental factors did not show significant associations. The lack of association between management and environmental factors with serostatus might be because all farms were exposed to a considerable number of potential factors. That all herds of this study were seropositive for neosporosis and the within-herd prevalence was considerable raises questions about how far the infection is spread in other dairy areas of Costa Rica.

Abortion, Veterinary↗

PubMed2001

Helicobacter infection and phospholipase A2 enzymes: effect of Helicobacter felis-infection on the expression and activity of sPLA2 enzymes in mouse stomach.

The murine gastric mucosa possesses very high secretory type phospholipase A2 activity. Northern and Western blots indicated that the pancreatic-type, sPLA2-IB represents the predominant form of sPLA2 enzymes present in the gastric mucosa. Both sPLA2-IB mRNA and protein in the gastric mucosa exceeded levels found in the pancreas, and in contrast to the pancreatic enzyme it was present primarily in the active state. The sPLA2-IB gene is not expressed in the murine small intestine and colon. Infection by the gastritis-inducing bacteria, Helicobacterfelis (H. felis) dramatically and time dependently decreased the PLA2 activity in the glandular stomach of the mouse strain, C57BL/6, sensitive to the organism, which appeared to be related to a decrease in the percentage of sPLA2-IB present in the active form. This bacterial-induced reduction in PLA2 activity was not observed in BALB/c mice that fail to develop gastritis in response to H. felis infection. C57BL/6 mice do not, while BALB/c mice express, the PLA2-II enzyme. The H. felis-induced reduction in sPLA2-IB activity may weaken the gastric barrier by reducing the local concentration of arachidonic and linoleic acid, liberated from membrane phospholipids, the major precursors of 'cytoprotective' prostaglandins. Data presented here suggest that both sPLA2-IB and sPLA2-II enzymes may contribute to the gastric response to Helicobacter infection.

Animals↗

PubMed2001

Phosphatidylcholine association increases the anti-inflammatory and analgesic activity of ibuprofen in acute and chronic rodent models of joint inflammation: relationship to alterations in bioavailability and cyclooxygenase-inhibitory potency.

We investigated whether chemical association of phosphatidylcholine (PC) to ibuprofen enhances the anti-inflammatory/analgesic activity of the nonsteroidal anti-inflammatory drug (NSAID) and whether any change in therapeutic action is due to alterations in drug bioavailability and cyclooxygenase (COX) inhibitory activity. Acute/chronic joint inflammation was induced in rats, by injection of Complete Freund's Adjuvant. In the acute study, rats were administered saline, ibuprofen, or PC-ibuprofen (at NSAID doses of 10, 25, and 50 mg/kg), and 2 h later the pain threshold of the affected joint to pressure was measured. PC-ibuprofen increased the pain threshold at all NSAID doses, whereas unmodified ibuprofen demonstrated analgesic activity at only the highest dose. In the chronic study, we investigated the effects of saline, PC-ibuprofen, and ibuprofen (administered at 15 and 25 mg/kg/day) on ankle thickness and pain threshold, and demonstrated that PC-ibuprofen had significantly greater anti-inflammatory and analgesic activity than ibuprofen, over a 30- to 60-day period. PC association resulted in reduced uptake (decreased Cmax), a modest increase in the area under the curve, and a longer t(1/2) of ibuprofen. We also demonstrated that PC-ibuprofen was a comparable or a more effective inhibitor of both 6-keto-prostaglandin F1alpha concentration of fluid collected from tissue in and around the inflamed stifle joint, and COX-2 activity in activated human umbilical vein endothelial cells. In conclusion, we have demonstrated that PC association results in increases in ibuprofen's anti-inflammatory and analgesic activity in rodent models of acute and chronic joint inflammation, and this effect may relate to alterations in drug bioavailability and COX-inhibitory potency.

Analgesics, Non-Narcotic↗

PubMed2000

Altered gastrin regulation in mice infected with Helicobacter felis.

Altered gastrin expression associated with Helicobacter pylori infection may contribute to the pathogenesis of peptic ulcer disease or gastric cancer in man, but gastrin has not been investigated in a murine model of Helicobacter infection. C57BL/6 mice were inoculated with Helicobacter felis and examined after 4-21 weeks for G and D cell numbers, antral gastrin and somatostatin mRNA, and luminal pH. In H. felis-infected mice, gastrin mRNA declined at four and six weeks after infection to 57% and 23%, respectively, of uninfected control values. Concurrently, somatostatin mRNA showed no change at four weeks and a modest 25% decrease at six weeks after infection. Similar reductions were noted in G and D cell numbers, resulting in a decrease in the G/D cell ratio after mice were infected with H. felis. Infected animals also showed a loss of parietal and chief cells, and an increased gastric pH. H. felis infection in C57BL/6 mice leads to an early suppression of G cell number and gastrin mRNA. These changes precede an alteration in somatostatin cell number and mRNA and, coupled with reductions in parietal and chief cells, may contribute both to severe impairment of gastric acid output and the potential for carcinogenic processes.

Animals↗

PubMed2000

Effect of bisphosphonates on surface hydrophobicity and phosphatidylcholine concentration of rodent gastric mucosa.

Bisphosphonates are a family of chemically related zwitterionic molecules that are used clinically to retard bone resorption in individuals with osteoporosis and associated skeletal diseases. Inflammation and ulceration of the upper gastrointestinal tract by a mechanism that relates to a topical irritant action is associated with the consumption of some bisphosphonates. In the present study, we investigated the effects of three bisphosphonate molecules, pamidronate, alendronate, and risedronate on the surface hydrophobicity and phosphatidylcholine (PC) concentration of the antral mucosa. We also examined how these surface changes related to mucosal injury in an established rat model, in which the test compounds were administered in combination with indomethacin. We initially determined that a combination of pamidronate (300 mg/kg) and indomethacin (40 mg/kg) induced a significant reduction in mucosal surface hydrophobicity and macroscopic lesion formation by 15 min and mucosal PC concentration by 30 min, with the magnitude of these changes increasing over the 4-hr study period. An equivalent dose of alendronate or risedronate in combination with indomethacin produced modest or no macroscopic injury, respectively, to the antral mucosa over the 4-hr study, although the bisphosphonates clearly induced surface injury and some glandular necrosis when examined at the light microscopic level. These bisphosphonates also induced modest decreases in antral surface hydrophobicity and mucosal PC concentration that appeared to be related to their injurious potential. In conclusion, the variable toxicity of bisphosphonates to the antral mucosa appears to be associated with their ability to compromise the surface hydrophobic phospholipid barrier of the tissue, with pamidronate > > > alendronate > risedronate. This bisphosphonate effect on the surface barrier may trigger the development of mucosal injury and possible ulceration.

Alendronate↗

PubMed2000

Longitudinal studies in the epidemiology of vesicular stomatitis on Costa Rican dairy farms.

Twenty-three Costa Rican dairy herds from an vesicular stomatitis (VS) endemic area were under an active surveillance between April 1997 and March 1999. Ninety-two confirmed cases of VS New Jersey were found. Factors associated with clinical cases of VS virus New Jersey were: Parity (animals of parity 4 or 5 were 5.3 times more likely to present a clinical case than animals of parity 3 and lower; on the other hand, animals of parity 6 and higher showed an odds 4.6 times greater than animals of parity 3 and lower.) Ecological life zone (animals in premountain moist forest were 7.4 times more likely to present clinical cases than animals in lower mountain rain forest). Factors associated with seropositivity at the time of birth were farm and breed (Jersey calves had an odds 14.7 times greater than Holstein calves). Seroconversion, defined as the first twofold increase in the titers of the blood, was associated with farm and showed four peaks during the study period, September (wet season) 1997, February (dry season) 1998, September 1998, and February 1999. Finally, time to event analysis showed difference between farms and age, older animals showed the first seroconversion earlier than younger animals.

Age Distribution↗

PubMed2000

Recombinant human lactoferrin is effective in the treatment of Helicobacter felis-infected mice.

Recombinant human lactoferrin possesses in-vitro antibiotic and anti-inflammatory activity similar to the native form. It was tested for in-vivo activity in mice infected with the gastritis-inducing bacterium Helicobacter felis. A two-week course of treatment with lactoferrin was sufficient to partially reverse both infection-induced gastritis and the infection rate, and fully reverse gastric surface hydrophobicity changes. A comparison of lactoferrin with amoxicillin and standard triple therapy revealed no differences in infection rate. These results show that recombinant human lactoferrin is effective in a mouse model of Helicobacter infection, and support further testing of this promising agent for this application.

Amoxicillin↗

PubMed2000

Neuropsychological sequelae of heat stroke: report of three cases and discussion.

Heat stroke includes neurologic impairment as a person's body temperature reaches 40.5 degrees C (105 degrees F) as a result of a failure of thermoregulation. The physiologic complications of heat stroke are well described in the literature. The domains of cognitive functioning affected and the severity of impairment resulting from heat stroke can vary from mild deficits in attention and memory to severe global dementia. There can also be changes in affect and personality that are equally debilitating. This article presents the neuropsychological test results of three active duty soldiers who suffered heat stroke and were tested within 2.5 months of injury.

Adolescent↗

PubMed1999

Interaction of indomethacin and naproxen with gastric surface-active phospholipids: a possible mechanism for the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs).

The possibility that the molecular mechanism underlying the topical gastric irritancy of nonsteroidal anti-inflammatory drugs (NSAIDs) may involve alterations in the surface-active properties of gastric phospholipids was investigated. Indomethacin and naproxen were intragastrically administered to rats and the hydrophobicity of the luminal surface of the stomach wall was assessed by contact angle analysis. Both NSAIDs have the ability to attenuate the phospholipid-related hydrophobic properties of the gastric mucosa by more than 80-85% in a dose-dependent fashion. Potential molecular interactions between both NSAIDs and surface-active phospholipids were analyzed using fluorescent probes. Indomethacin has the ability to displace, in a dose-dependent manner, ANS (1-anilino-8-naphthalene sulphonate), a fluorescent anionic probe previously bound to the head group of phosphatidylcholine molecules. Estimations of the resonance fluorescence transfer between naproxen and the surface probe ANS or the hydrophobic probe, pyrene, bound to dipalmitoylphosphatidylcholine (DPPC) vesicles revealed that naproxen diffuses within the phospholipid bilayers. The dynamic of the gastric lipid material extracted from the surface scraping material (SSM) of the mucosa was altered by the NSAID as shown by the increase in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) (at 25 degrees, rSSM = 0.106+/-0.006, rssM + indomethacin = 0.137+/-0.005, and rSSM + naproxen = 0.133+/-0.007, P < 0.001). The thermodynamic behavior of a model bilayer containing DPPC was also perturbed by the NSAIDs tested. These results provide evidence that NSAIDs may reduce the ability of gastric surface-active phospholipids to form a hydrophobic protective layer.

Animals↗

PubMed1999

Attenuation of hydrophobic phospholipid barrier is an early event in Helicobacter felis-induced gastritis in mice.

Helicobacter pylori infection has been linked to the development of gastritis which can then progress to a number of disease entities including peptic ulcer disease and gastric cancer. Since the pathogenic mechanism by which the bacteria causes gastritis is unresolved, we employed a model system, the H. felis-infected mouse to investigate the temporal relationship between bacterially-induced alterations in the hydrophobic phospholipid barrier of the stomach and the development of gastritis. In the present study, C57BL/6 mice were inoculated with 10(9) CFU of H. felis and the changes in gastric wet weight, histology, surface hydrophobicity, phospholipid/phosphatidylcholine concentration, phospholipase A2 activity, and the pH of collected gastric juice were measured 0.5-2 months postinoculation. In related experiments, we investigated the effects of treating H. felis infected mice with antibiotic/ bismuth therapy on the above gastric properties. It was determined that both gastric surface hydrophobicity and phospholipid composition were significantly attenuated as early as 2-4 weeks postinfection, preceding signs of mucosal inflammation and glandular atrophy as indicated by increases in gastric wet weight, pH and a disappearance in parietal cells. These early H. felis-induced changes in gastric surface hydrophobicity and phospholipid concentration were reversed by antibiotic/bismuth therapy. Based on these results we conclude that H. felis infection induces an early transformation of the stomach from a hydrophobic to an acid-sensitive hydrophilic state that may trigger the subsequent development of gastritis.

Animals↗

PubMed1999

Effect of ranitidine bismuth citrate on the phospholipase A2 activity of Naja naja venom and Helicobacter pylori: a biochemical analysis.

BACKGROUND: Helicobacter pylori has become recognized as a fundamental pathogen in the development of gastritis and peptic ulcer disease. Bismuth compounds in combination with antibiotics are widely used to treat H. pylori associated peptic ulcer disease. METHODS: In this study we measured and analysed the inhibitory effect of ranitidine bismuth citrate (RBC, Pylorid, Tritec) on the activity and kinetics of phospholipase A2 (PLA2) (E.C.3.1.1.4) of commercial cobra (Naja naja) venom and H. pylori (French press lysates) using L-alpha-dipalmitoyl-(2[1-14C]palmitoyl)-phosphatidylcholine as substrate. RESULTS: Our data suggest that RBC might exert a dose-dependent uncompetitive inhibition on PLA2 activity of both H. pylori and Naja naja venom. the inhibitory effect of RBC on the PLA2 activity cannot be abolished by the optimal concentration of calcium (10 mM), indicating its mechanism to be unrelated to the displacement of calcium from the activation site of the enzyme. CONCLUSION: Our results suggest that one of the mechanisms by which bismuth compounds are therapeutically effective in the treatment of H. pylori associated gastritis is by inhibiting the activity of the degradative PLA2 enzyme secreted by H. pylori. As a consequence of the inhibitory action of RBC on PLA2 of the bacteria, the extracellular and/or intracellular phospholipid components of the gastric mucosal barrier are preserved.

Animals↗

PubMed1999

Phospholipid association reduces the gastric mucosal toxicity of aspirin in human subjects.

OBJECTIVE: In previous studies on rats, we have shown that aspirin (ASA)-induced injury to the gastric mucosa is markedly reduced or completely abolished if ASA is chemically associated with the phospholipid, phosphatidylcholine (PC). We have also shown that the protective effect of PC does not influence the ability of ASA to inhibit mucosal cyclooxygenase (COX) activity in the stomach and other tissues. We therefore sought to assess the effect of PC-associated ASA (ASA/PC) on the gastric mucosa of normal volunteers and to compare the results with the use of ASA alone. METHODS: Sixteen normal healthy subjects were administered ASA or ASA/PC in a randomized, double-blind, crossover study. The subjects received ASA in a dose of 650 mg three times a day for 3 days or an equivalent dose of ASA chemically associated with PC. Endoscopy was performed at baseline and again on the morning of day 4, after the subjects had taken the final dose of the test drug. On both occasions, antral biopsy specimens were obtained for the assessment of mucosal COX activity and prostaglandin concentration. RESULTS: The number (mean +/- SD) of gastric erosions seen with the ASA/PC formulation was significantly less than when ASA was used alone (8.7 +/- 10.7 vs 2.9 +/- 4.3; p < 0.025). A similar trend was seen in the duodenum but the difference was statistically not significant. The antral mucosal COX activity, as well as the level of prostaglandin 6-keto PGF1alpha, were reduced significantly (80-88%) and to a similar extent by both ASA and ASA/PC. CONCLUSIONS: The present study shows that acute aspirin-induced damage to the gastric mucosa can be reduced by chemically associating ASA with PC. The mechanism of mucosal protection provided by this compound is not related to any alteration in the ability of ASA to inhibit mucosal COX activity. We believe this protection is attributable to the maintenance of the defensive hydrophobic barrier of the gastric mucosa.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Antibiotic properties of bovine lactoferrin on Helicobacter pylori.

To investigate a potential new treatment for gastric Helicobacter pylori infection, we have examined the use of the natural antibiotic lactoferrin, found in bovine milk, for activity against Helicobacter species both in vitro and in vivo. Lactoferrin was bacteriostatic to H. pylori when cultured at concentrations > or =0.5 mg/ml. Growth of H. pylori was not inhibited by another milk constituent, lysozyme, or by a metabolite of lactoferrin, lactoferricin B, but growth was inhibited by the iron chelator deferoxamine mesylate. Lactoferrin inhibition of growth could be reversed by addition of excess iron to the medium. Lactoferrin in retail dairy milk was found to be more stable intragastrically than unbuffered, purified lactoferrin. Treatment of H. felis-infected mice with lactoferrin partially reversed mucosal disease manifestations. It is concluded that bovine lactoferrin has significant antimicrobial activity against Helicobacter species in vitro and in vivo. Bovine lactoferrin should be further investigated for possible use in H. pylori infections in man.

Animals↗

PubMed1998

Effect of pepper and bismuth subsalicylate on gastric pain and surface hydrophobicity in the rat.

BACKGROUND: The mechanism by which dietary pepper causes dyspepsia and epigastric pain is poorly understood, as is the ability of bismuth subsalicylate (BSS) to relieve these symptoms. AIM: To investigate the ability of black pepper, red pepper and BSS to affect gastric surface hydrophobicity and induce/relieve visceral pain in rat model systems. METHODS: Fasted rats were administered intragastrically Vivonex containing varying concentrations of either black or red pepper (0-200 mg/mL) and gastric contact angles were read after 1-24 h. Some rats were post-treated with BSS (2.0-17.5 mg/mL) and contact angles were read after 2-18 h. To study pain sensitivity in rats treated with pepper/BSS, we compared tail-flick latencies after the application of radiant heat. RESULTS: Both black and red pepper rapidly (< 1 h) induced a decrease in gastric surface hydrophobicity in a dose-dependent fashion. This spice-induced increase in surface wettability was long-lasting, could be enhanced in the presence of ethanol and reversed by post-treating the rats with BSS. Both black and red pepper induced an increase in pain sensitivity, consistent with the presence of gastric pain, which could also be reversed by post-treating the rats with BSS. CONCLUSION: Both black and red pepper may induce epigastric pain by removing the stomach's hydrophobic lining and activating intramucosal pain receptors. BSS may provide relief from postprandial dyspepsia by restoring the stomach's non-wettable properties.

Animals↗

PubMed1996

Nonsteroidal anti-inflammatory drug and phospholipid prodrugs: combination therapy with antisecretory agents in rats.

BACKGROUND & AIMS: The gastrointestinal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are reduced by antisecretory agents. The effects of combination therapy on the gastrointestinal toxicity and therapeutic activity of free and phospholipid-associated NSAIDs were investigated in rats. METHODS: Fasted rats, pretreated with either saline or an antisecretory dose of omeprazole, ranitidine, or cimetidine, were intragastrically administered saline, aspirin, or indomethacin. In ulcer models, gastric lesions in aspirin-treated rats and intestinal bleeding in indomethacin-treated rats were measured. For antipyretic and analgesic activity, rectal body temperature in febrile rats and the rats' pain sensitivity to pressure applied to an inflamed limb were measured, respectively. RESULTS: NSAID-induced gastrointestinal ulceration and bleeding were reduced in rats pretreated with antisecretory agents and abolished in rats administered phospholipid-associated NSAIDs in combination with inhibitors of acid secretion. The antipyretic and analgesic activity of both NSAIDs was attenuated in rats pretreated with an antisecretory agent. This pH-dependent block in therapeutic activity was overcome if the NSAID was preassociated with a phospholipid to enhance the drug's lipophilic characteristics. CONCLUSIONS: Combination therapy of antisecretory agents and NSAIDs, chemically associated with phospholipids, has distinct advantages with regard to both low gastrointestinal toxicity and restored therapeutic activity.

1,2-Dipalmitoylphosphatidylcholine↗