Development and validation of a tissue cage model of acute inflammation in the cat.

Four cylindrical silicon tissue cages (TC, internal volume: 6.7 ± 0.11 cm(3)) were inserted subcutaneously in 29 young healthy cats. A mild inflammatory reaction was induced by intracaveal injection of 1 mL of a 2%λ-carrageenan solution. TC exudate was subsequently sampled at predetermined times (up to 120 h) to measure exudate leucocyte counts and the concentrations of protein and eicosanoids. TC remained in situ for 9-10 months and were well tolerated. Leucocyte counts peaked at 34 h (50.1 ± 57.6 × 10(3) cells/mm(3) ) and returned towards baseline after 72 h. Protein concentration increased from 26.2 ± 2.7 g/L to a peak of 35.9 ± 6.0 g/L at 12 h before returning to baseline at 48 h. Exudate prostaglandin (PG)E(2) concentration peaked at 24 h (11.7 ± 13.7 ng/mL) and returned to baseline by 120 h. Repeated collection of fluid from noninjected cages did not increase transudate PGE(2). Ketoprofen (2 mg/kg, subcutaneously) suppressed exudate PGE(2) at 24 h. The carrageenan-stimulated TC model is an ethical and novel means of investigating soft tissue inflammation in the cat, in which exudate PGE(2) acts as surrogate marker of cyclooxygenase-2 activity. This model will facilitate the investigation of in vivo pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in this species.

Grape pomace improves performance, antioxidant status, fecal microbiota and meat quality of piglets.

In the present study, grape pomace (GP) was used as feed additive in the diet of weaned piglets in order to develop innovative feedstuffs and to investigate their potential beneficial effects on welfare, productivity and meat quality. For examining the antioxidant capacity of the experimental feeds, 24 piglets of 20 days old were assigned to two experimental groups receiving standard or experimental diet for 30 days. Blood and tissues collections were performed at four different time-points, 2, 20, 35 and 50 days post birth. The collected tissues were brain, heart, kidney, liver, lung, quadriceps muscle, pancreas, spleen and stomach. The following oxidative stress markers were assessed: reduced glutathione (GSH), catalase activity, total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), protein carbonyls (CARB) and H2O2 decomposition activity. The effect on bacterial growth was assessed by examining microbial populations in piglets' fecal microbiota. Furthermore, the average daily gain (ADG) was calculated and the fatty acid profile of quadriceps muscle was assessed. The results showed that piglets fed with the diet supplemented with GP, had significantly increased antioxidants mechanisms in almost all the tissues as shown by increases in GSH, H2O2 decomposition activity and TAC compared with control group. Piglets fed with the experimental diet exhibited decreased oxidative stress-induced damage to lipids and proteins as shown by decreases in TBARS and CARB in GP group compared with control. In addition, the experimental diet increased significantly ADG (by 23.65%) (P<0.05) and enhanced the growth of facultative probiotic bacteria (by up to 1.2 log colony forming units (CFU)/g) (P<0.05) and lactic acid bacteria (by up to 2.0 log CFU/g) (P<0.05) in GP group compared with the control group. GP supplementation inhibited the growth of pathogen populations such as Enterobacteriacae (by up to 1.8 log CFU/g) (P<0.05) and Campylobacter jejuni (by up to 1.0 log CFU/g) (P<0.05). Regarding fatty acid composition of meat, GP inclusion in piglets' diet increased significantly n-3 fatty acids (EPA; C20 : 5n-3, DHA; C22 : 6n-3, α-linolenic acid; C18 : 3n-3) and decreased significantly n-6/n-3 ratio compared with control (P<0.05). The results suggested that dietary GP supplementation may have a beneficial impact on piglets' welfare and may improve productivity as well as meat quality.

Brain-computer interface: a reciprocal self-regulated neuromodulation.

Brain-computer interface (BCI) is a system that records brain activity and process it through a computer, allowing the individual whose activity is recorded to monitor this activity at the same time. Applications of BCIs include assistive modules for severely paralyzed patients to help them control external devices or to communicate, as well as brain biofeedback to self regulate brain activity for treating epilepsy, attention-deficit hyperactivity disorder (ADHD), anxiety, and other psychiatric conditions, or to enhance cognitive performance in healthy individuals. The vast majority of BCIs utilizes non-invasive scalp recorded electroencephalographic (EEG) signals, but other techniques like invasive intracortical EEG, or near-infrared spectroscopy measuring brain blood oxygenation are tried experimentally.

The current range of neuromodulatory devices and related technologies.

The pace of technology dictates changes in every aspect of human life. Medical profession is not an exception. The development of sophisticated electronic devices has radically influenced diagnosis and therapy. Today neurosurgical science is revolutionized with numerous implanted and non-implanted devices that modulate and stimulate the nervous system. Physicians, patients and non-technical experts involved in this field need to understand the core mechanisms and the main differences of this technology so that they can use it effectively. It will take years until clinicians reach a "consensus" about the use of these devices, but in the course of action objective information about the current status of the methods and equipment, and the technical, biological, and financial complications that arise in practice will speed up their public approval and acceptance.

Optical purity determination, conformer populations and 1H NMR spectral simplification with lanthanide shift reagents--part IX. A method for improved analytical precision for "DOEt", 2,5-dimethoxy-4-ethylamphetamine.

The 60 MHz (1)H NMR spectra of the potent hallucinogen 2,5-dimethoxy-4-ethylamphetamine ("DOEt"), 1, have been studied in CDCl(3) at 28 degrees with the achiral shift reagent, tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium(III), 2, and the chiral reagents tris[3-(trifluoromethylhydroxymethylene)-d-camphorato] europium(III), 3, and tris[3-(heptafluoropropylhydroxymethylene)-d-camphorato] europium(III), 4. Distinct enantiomeric shift differences, DeltaDeltadelta, were observed for the amphetamine CH(3) and the adjacent CH resonances using either 3 or 4 that permit direct optical purity determinations. A novel use of an external computing integrator as an accessory to a basic NMR is described; interfacing these instruments permits improved analytical precision for the reported optical purity determinations using nonracemic mixtures of known compositions. Relative abundances of the different conformers with respect to C(alpha)C(beta) bond rotation in the arylethylamine moiety is discussed based on coupling constants. Results are compared with the related hallucinogen, 3,4-methylenedioxyamphetamine.

Optical purity determination and (1)H-NMR spectral simplification with lanthanide shift reagents - VIII. An indacrinone precursor, 6,7-dichloro-5-methoxy-2-methyl-2-phenyl-1-indanone.

The 60 MHz (1)H NMR spectra of racemic 6,7-dichloro-5-methoxy-2-methyl-2-phenyl-1 indanone (1) have been studied with the achiral shift reagent, tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium (III) (2) and the chiral reagents, tris[3-(trifluoromethylhydroxymethylene)-d-camphorato] europium (III) (3) and tris[3-(heptafluoropropylhydroxymethylene)-d-camphorato] europium (III) (4). While some enantiomeric shift differences, DeltaDeltadelta, were seen for some protons of 1 with 3, dramatically larger values were obtained with 4. The latter would be the reagent of choice for direct optical purity determinations of 1 using the 2-methyl resonance. Optimum conditions would use a 4:1 molar ratio of 0.1-0.25, providing near-baseline resolution for the peaks and freedom from overlap with interfering peaks. Less than 3% of the minor enantiomer should be detectable. The results are consistent with lanthanide complexation at the carbonyl. The value of DeltaDeltadelta for the C(2) methyl of 1.1 ppm with a 4:1 molar ratio of 1.50 appears to be among the highest reported values for simple ketones with 3 or 4.

(1)H NMR spectral simplification with achiral and chiral lanthanide shift reagents. Tranylcypromine, trans-2-phenylcyclopropanamine.

The 60 MHz (1)H NMR spectra of racemic tranylcypromine, 1, have been studied with the achiral shift reagent, tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium(III), 2, and the chiral tris[3-(trifluoromethylhydroxymethylene)-d-camphorato] europium(III), 3. Appreciable values of the enantiomeric shift differences, DeltaDeltadelta, were observed for each cyclopropyl proton except for the proton beta and trans to the amino group (furthest from the expected europium complexation site). The proton alpha to the amino group showed DeltaDeltadelta as high as about 38 Hz for a 3:1 ratio of 0.71; the DeltaDeltadelta decreased at higher 3:1 ratios. Optical purity evaluations should be most practical using this alpha proton with 3:1 ratios near 1.07 to minimize interference due to peak overlap.

Quantitative NMR assay for aspirin, phenacetin, and caffeine mixtures with 1,3,5-trioxane as internal standard.

The method for (1)H NMR determination of aspirin, phenacetin and caffeine (APC) mixtures has been improved by the use of 1,3,5-trioxane as an internal standard. The trioxane absorption occurs in a peak-free region of the spectrum and produces no interferences with any of the analytes. Compared to the original method with caffeine as an external standard, the present method appears to offer better accuracy and precision. Average errors relative to the correct results were: aspirin, 1.0%; phenacetin, 0.8%; and caffeine 1.8%, for known standard mixtures. Coupling constants, (1)J((13)CH), were determined for the methyl groups of aspirin and caffeine and for the trioxane methylene group to clarify potential (13)C satellite interferences.

1H NMR spectral simplification with achiral and chiral lanthanide shift reagents--IV. Thiopental and barbiturate analogues.

The 60 MHz (1)H NMR spectra of racemic thiopental, 1, have been studied with the achiral shift reagent, tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium(III), 2, and the chiral tris[3-(trifluoromethylhydroxymethylene)-d-camphorato] europium(III), 3, and tris[3-(heptafluoropropylhydroxymethylene)-d-camphorato] europium(III), 4. Enantiomeric shift differences, DeltaDeltadelta, were clearly observed for all three methyl signals of 1 with 3 or 4, with larger values obtained using the former reagent. Thus, a 0.216 molal solution of 1 in CDCl(3) at 28 degrees C with a 3:1 molar ratio of 0.359 displayed DeltaDeltadelta values of about 17 Hz for the proximal methyl of the methylbutyl group (at the chiral centre), 13 Hz for the CH(3) of the ethyl group, and 6 Hz for the distal CH(3) of the methylbutyl group. Results are compared for those obtained with 2 and 3 using secobarbital, talbutal, butabarbital and pentobarbital.

Peritalar dislocation: a follow-up report of 21 cases.

A total of 21 patients with peritalar dislocation, treated during the last 15 years in our hospital are reviewed. Of these, 18 had medial and 3 lateral dislocations. At follow-up, 10 patients with medial dislocation experienced either occasional pain due to the limitation of subtalar movements, or chronic pain due to severe osteoporosis of the hindfoot. All these patients with lateral dislocation had severe chronic pain, which was alleviated by subtalar arthrodesis in two of them. It is concluded that peritalar dislocation produces varying degrees of disability in the majority of patients with medial dislocation and serious disability in all patients with lateral dislocation. This is due to the severity of the soft tissue damage and the prolonged immobilization of the foot without bearing weight. It is essential to mobilize the foot as soon as possible after the injury.

Intravenous tobramycin and metronidazole as an adjunct to corticosteroids in acute, severe ulcerative colitis.

OBJECTIVES: The aim of this study was to evaluate the role of metronidazole and tobramycin as an adjunct to corticosteroids in acute, severe ulcerative colitis. METHODS: Thirty-nine consecutive patients with severe ulcerative colitis were randomized on admission to the hospital to receive intravenously either metronidazole (0.5g tid) and tobramycin (4 mg/kg tid) (n = 19), or placebo (n = 20). In addition, they were given parenteral nutrition, intravenous hydrocortisone (100 mg qid) and hydrocortisone enemas (100 mg bid). All patients were assessed after 10 days of continuous treatment, or at any time a severe complication occurred. RESULTS: Twelve of 19 patients (63.15%) treated with antibiotics and 13/20 patients (65%) with placebo showed substantial improvement. Seven patients in each group did not improve (n = 9), or developed complications (n = 5) and underwent emergency colectomy without perioperative deaths or late deaths. CONCLUSIONS: These results do not support the routine use of intravenous tobramycin and metronidazole in the treatment of severe ulcerative colitis.

Prospective, randomized, investigator-blind trial of Helicobacter pylori infection treatment in patients with refractory duodenal ulcers. Healing and long-term relapse rates.

In this study, 26 patients with duodenal ulcers refractory to treatment with H2-receptor antagonists for 8-12 weeks were randomly assigned to eight weeks of treatment with colloidal bismuth subcitrate (120 mg four times a day) alone (N = 12) or in combination with tetracycline hydrochloride (500 mg four times a day, days 0-14) and metronidazole (500 mg three times a day, days 15-28). Symptoms were scored and endoscopy, histology, and CLO tests were performed before, on completion of treatment, and 3, 6, 12, and 18 months after treatment. Treatment was considered successful when Helicobacter pylori was not detected by CLO tests and Warthin-Starry stains on gastric biopsies taken from antrum, body, and fundus. On triple therapy, ulcers healed in 12/14 patients (85.71%) and 10/14 (71.42%) patients became Helicobacter pylori-negative. On bismuth, only one patient became Helicobacter pylori-negative (8.33%, P < 0.0001), but ulcers healed in 8/12 patients (67%, P = NS). Six patients on bismuth, whose ulcers remained unhealed or relapsed early after healing, were offered triple therapy, which resulted in ulcer healing in three and Helicobacter pylori clearance in two patients. At 18 months, none of the Helicobacter pylori-negative patients had ulcer relapse. On the contrary, ulcers relapsed in all but one patient, who remained Helicobacter pylori-positive. Smoking and drinking did not influence the therapeutic outcome. The data confirm previous reports that many duodenal ulcers are infectious and therefore curable.

Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains remission in ulcerative proctitis and proctosigmoiditis.

PURPOSE: The aim of this study was to compare the efficacy of intermittent therapy with mesalazine enemas and continuous oral mesalazine to maintain remission of distal ulcerative colitis or proctitis. METHODS: Thirty-eight patients with distal ulcerative colitis (n = 17) or ulcerative proctitis (n = 21) in clinical, endoscopic, and histologic remission were randomly assigned to receive either oral mesalazine (0.5 g three times/day, Eudragit L coating, n = 19) or intermittent therapy with mesalazine enemas (4 g of 5-aminosalicylic acid enema every third night, n = 19). Both groups were comparable in regard to sex, age, age at disease onset, extent and duration of disease, number and mode of treatment of previous attacks, and time in remission. Patients were reviewed at the beginning of the study and, subsequently, at two-month intervals for 24 months or until a relapse occurred. At each visit, diaries were reviewed and clinical and laboratory assessments were performed. Sigmoidoscopy was carried out and biopsies were obtained by a blinded observer. Histology was assessed without knowledge of the patient's clinical state or treatment category. RESULTS: At the end of the study, 6 of 19 patients on oral mesalazine (32 percent) and 14 of 19 patients on mesalazine enemas (74 percent) were still in full remission (log rank test: 15.28, P < 0.001). Differences in relapse rates between groups were significant even when data were stratified by extent of disease (P < 0.01). In the oral group, six and seven patients relapsed at 12 and 24 months, respectively. In the enema group, three and two relapses occurred in the first and second year of the study, respectively. All patients complied with the treatment satisfactorily and there were no dropouts. CONCLUSION: These results suggest that intermittent therapy with mesalazine enemas is more effective than continuous oral mesalazine in maintaining remission in patients with distal ulcerative colitis and proctitis.

The role of colonoscopy in the differential diagnosis of acute, severe hemorrhagic colitis.

BACKGROUND AND STUDY AIMS: This study assesses the diagnostic value of colonoscopy performed at an early stage of a first attack of acute, severe hemorrhagic colitis. PATIENTS AND METHODS: One hundred fourteen consecutive patients were prospectively studied. The colonoscopic diagnosis was compared with the final diagnosis of the colitis, which was based on clinical, microbiological, endoscopic, and histological criteria during the acute illness, but also on the results of a thirty-month follow-up of the patients aiming to confirm whether the colitis was relapsing or nonrelapsing in nature. RESULTS: The colonoscopic diagnosis was ulcerative colitis (UC) in 40, Crohn's disease in four, and infective colitis (IC) in 70 patients. The endoscopic diagnosis was finally confirmed in all 40 UC patients and in 68 of 70 (97.1%) IC patients. Two patients with an initial endoscopic and histological diagnosis of IC presented with typical attacks of UC 28 and 30 months later, respectively. Prominent endoscopic appearances in IC were mucosal edema, erythematous areas, hemorrhagic spots, bleeding, microaphthoid ulcers, and luminal exudate. Although rectal sparing was occasionally seen, endoscopic lesions were continuous and severe in the distal colon, but were patchily and unevenly distributed in other parts of the colon in IC. In UC, prominent colonoscopic findings were bleeding, mucosal friability, granularity, and ulceration; lesions were continuously distributed in the involved area. CONCLUSIONS: Colonoscopy is a useful procedure in the differential diagnosis of severe bloody diarrhea of unknown cause.