Biomedical subjects

J T Green

Publications and source records attributed to J T Green.

At least 19 recordsLinked to original sources

PubMed2006

Does endoscopy diagnose early gastrointestinal cancer in patients with uncomplicated dyspepsia?

BACKGROUND: Recent guidelines from NICE have proposed that open access gastroscopy is largely limited to patients with "alarm" symptoms. AIMS AND METHODS: This study reviewed the outcome of all our patients with verified oesophageal or gastric carcinoma who presented with uncomplicated dyspepsia to see if endoscopic investigation is warranted in this group. All patients with histologically verified upper gastrointestinal (GI) cancers who presented over a period from 1998 to 2002 were identified. Their presenting symptoms, treatment, and outcome were analysed. RESULTS: 228 upper GI cancers (119 oesophageal, 109 gastric; mean age 72 years (29-99 years); 130 male, 82 female) were identified in 11 145 endoscopies performed. Only 14 patients (6.2%) presented without alarm symptoms; three patients were under 55 years of age and all had gastric carcinoma-one of these had chronic diarrhoea only. Eleven had dyspepsia or reflux symptoms only, and two were under surveillance for Barrett's oesophagus. Only five patients had a curative surgical resection and are still alive two-six years from diagnosis. A sixth patient had a curative operation but died of a cerebrovascular accident one year later. The remaining eight patients unfortunately had either metastatic disease or comorbidity, which precluded surgery. All of these died within two years of diagnosis, mean survival 10 months. CONCLUSION: Only five patients with dyspepsia and no alarm symptoms had resectable upper GI malignancies over a four year period. Limiting open access gastroscopy to those with alarm features only would "miss" a small number of patients who have curable upper GI malignancy.

Adult↗

PubMed2006

Performance of beef heifers grazing stockpiled fescue as influenced by supplemental whole cottonseed.

The objectives of this study were to determine the composition of stockpiled fescue from December through February over 2 yr and to determine the performance of heifers grazing stockpiled fescue with or without supplemental whole cottonseed. In early December, 36 heifers (initial BW 277 +/- 0.70 kg, yr 1; 266 +/- 2.2 kg, yr 2; and initial BCS of 5.0 +/- 0.04) were assigned randomly to 6 groups. Each group was assigned randomly to a 2.4-ha tall fescue pasture (98% endophyte infected), which had received 76 kg of N/ha on September 1. Group was the experimental unit for all measures. Forage DM available during grazing (to ground level) averaged 3,913 and 5,370 kg/ha in yr 1 and 2, respectively. The pasture was strip-grazed for 83 d, with daily forage allocation. Three groups were fed whole cottonseed (0.90 kg of DM/heifer; 24.4% CP, DM basis) daily at 0.33% of BW, and a small amount of a corn-based concentrate (0.19 kg of DM/heifer) to assure complete cottonseed consumption. Nutritive value of forage (dry basis) was determined each week by sampling each pasture to the 5-cm target grazing height. Forage disappearance was estimated every 2 wk from pre- and postgraze forage mass. Forage CP was 16.8% in yr 1 and 12.6% in yr 2. In vitro true organic matter digestibility (IVTOMD) was 82.0 and 71.9%, and ADF was 25.9 and 30.7% in yr 1 and 2, respectively. Most indicators of forage quality declined slightly through the winter, although they recovered in late winter in yr 1. The proportion of fescue that was green declined (P < 0.05) from December (79% in yr 1 and 64% in yr 2) to February (62% in yr 1 and 52% in yr 2). Green tissue averaged 20.4 and 15.2% CP, 91 and 87% IVTOMD, and 22.1 and 23.3% ADF in yr 1 and 2, respectively. Brown tissue averaged 10.3 and 8.5% CP, 64 and 62% IVTOMD, and 35.7 and 37.4% ADF in yr 1 and 2, respectively. Shrunk ADG (0.46 vs. 0.56 kg/d in yr 1 and 0.23 vs. 46 kg/d in yr 2) and change in BCS (- 0.03 vs. 0.33 in yr 1 and 0.13 vs. 0.5 in yr 2) was greater (P < 0.05) for supplemented heifers. Supplemented heifers had greater serum urea nitrogen in yr 1 (9.5 vs. 10.5 mg/dL; P < 0.07) and yr 2 (7.2 vs. 8.6 mg/dL; P < 0.01). Forage disappearance was similar between supplemented and unsupplemented heifers (3.19 vs. 3.39 kg.heifer(-1).d(-1) in yr 1 and 4.14 vs. 4.17 kg.heifer(-1).d(-1) in yr 2, respectively). Heifers responded to supplementation, but performance was lower than expected based on forage nutrient content.

Animal Feed↗

PubMed2005

Intake, digestion, and N metabolism in steers fed endophyte-free, ergot alkaloid-producing endophyte-infected, or nonergot alkaloid-producing endophyte-infected fescue hay.

A digestion and N balance trial was conducted to compare effects of traditional endophyte-infected (E+), endophyte-free (E-), and nontoxic endophyte infected (NE; MaxQ; Pennington Seed, Inc., Madison, GA) Jesup tall fescue (Festuca arundinacea Schreb.) hay on digestion and N retention in steers. Hay composition (DM basis) was as follows: E+ (10.8% CP, 59.9% NDF, and 29.4% ADF), E- (11.8% CP, 58.5% NDF, and 28.4% ADF), and NE (11.6% CP, 58.6% NDF, and 28.3% ADF). Eight Polled Hereford steers (initial BW 240 +/- 9 kg) were used in a replicated, 3 x 3 Latin square design, with an extra steer allotted to each square. Steers were fed ad libitum for 14 d, followed by a 9-d adaptation to restricted intake (based on the animal with the lowest ad libitum intake for the square) and a 5-d fecal and urine collection. Water intake (20.2 L/d) and urine output (7.40 L/d) did not differ (P > 0.10) during the collection period. Plasma prolactin concentration was less (P < 0.05) for steers on the E+ hay (8.83 ng/mL) than for those on the E- hay (18.03 ng/mL) and intermediate for steers on the NE hay (12.65 ng/mL). Endophyte-infected hay differed (P < 0.05) from E- and NE in ad libitum DMI (5.02 vs. 5.62 and 5.61 kg/d, respectively) and ad libitum DMI as a percentage of BW (1.86 vs. 2.06 and 2.06%, respectively). Restricted DMI during the fecal and urine collection was lower (P < 0.05) for E+ hay than for E- (5.04 vs. 5.24 kg/d), and NE was intermediate (5.19 kg/d). Dry matter digestibility was lower (P < 0.05) for E+ compared with E- and NE (62.3 vs. 67.0 and 65.9%, respectively). Digestibility of ADF was lower (P < 0.05) for E+ than for E-, and was intermediate for NE (61.5, 66.0, and 63.9%, respectively). There were no differences for NDF, cellulose, or hemicellulose digestibilities among hay types. Crude protein digestibility was higher (P < 0.05) for E- and NE than for E+ (54.3 and 52.5 vs. 48.1%, respectively). Nitrogen retention was lower (P < 0.01) for E+ than for E- or NE (15.6 vs. 22.7 or 23.0 g/d, respectively). Hay type did not influence plasma urea N, urine urea N output, or urine urea N as a percentage of urinary N. Results from this study indicate that E+ tall fescue hay was lower in ad libitum DMI, DM digestibility, and N retention than NE or E- hays with similar chemical composition. Hay from NE and E- fescue had nearly identical composition, and did not differ for any variable measured.

Animal Nutritional Physiological Phenomena↗

PubMed2004

Differential effect of nitric oxide synthase inhibition on sigmoid colon longitudinal and circular muscle responses to nicotine and nerve stimulation in vitro.

BACKGROUND: Nicotine has been shown to release nitric oxide from nerves in human sigmoid colon. This effect has been used to investigate the innervation and functional relationship of the longitudinal and circular muscle layers. METHODS: Strips of longitudinal and circular muscle were obtained from 19 patients with colorectal cancer. The strips from ten patients were subjected to electrical field stimulation (EFS) in vitro using stimulus parameters for selective stimulation of nerves. The effect of nicotine 1-10 micromol/l on EFS responses was then measured in the presence and absence of a nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (L-NAME) 200 micromol/l. The effect of nicotine on spontaneous activity was investigated in the muscle strips from the other nine patients. RESULTS: Both longitudinal and circular strips responded to EFS with contraction. The time to achieve a peak contractile response (time to peak; TTP) was significantly longer (P<0.001) in circular strips. L-NAME reduced the mean(s.e.m.) TTP in circular muscle from 23.3(2.0) to 17.2(1.5) s (P=0.007) and altered its pattern of response to resemble that of longitudinal muscle. Nicotine 10 micromol/l reduced the contraction to EFS in circular (P<0.001) but not in longitudinal (P=0.347) muscle. The nicotine-induced reduction in circular muscle contraction was blocked by L-NAME 200 micromol/l (P=0.005). CONCLUSION: These findings suggest that nitric oxide release on neural stimulation is greater in circular than in longitudinal muscle.

Colon, Sigmoid↗

PubMed2004

Massive pleural effusion and marked increase of CA-125.

The tumour associated CA-125 antigen is widely used in monitoring ovarian carcinoma. In women with a massive pleural effusion and ascites, markedly increased CA-125 levels may lead to an erroneous diagnosis of ovarian cancer. Very high levels of tumour markers may be present in patients with benign pleural effusion, ascites, and chronic liver disease. Raised levels of tumour markers in serum or pleural fluid, in the absence of positive cytology, should be interpreted with caution.

Adult↗

PubMed2003

Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a disease largely of non-smokers, in which nicotine is of therapeutic value. The mode of action is unknown, but may involve nicotinic acetylcholine receptors (nAChRs) in the bowel wall. AIM: To investigate the presence of nAChRs in rectal mucosa, and the effect of smoking and nicotine on their expression. DESIGN: Prospective case-control study. METHODS: In situ hybridization (ISH) and immunocytochemistry (ICC) were used to show alpha3 nAChRs in colonic mucosa. Rectal mucosa was examined from controls (n=55) and patients with inactive UC (n=62), both smokers and non-smokers, by ICC, using two antibodies to show the density and distribution of receptors in the mucosa. Non-smokers with UC (n=43) were given transdermal nicotine or placebo patches for 6 months, and rectal biopsies, taken before and after treatment, were examined by ICC to show nAChRs. RESULTS: In normal colon, ISH and ICC showed alpha3 subunit in a wide variety of cells, including mucosal epithelium. In rectal biopsies, neither smoking nor nicotine influenced the expression of alpha3 immunoreactivity in epithelium, either in controls or UC. However, controls had a significantly greater density of immunodetectable mucosal epithelium alpha3 subunit, compared with UC patients. DISCUSSION: The presence of nAChRs in colonic epithelium may be pertinent to the beneficial effect of nicotine in UC, but since neither smoking nor nicotine treatment is associated with any change in the expression of epithelial alpha3 nAChRs, the effect may be due to functional changes in the receptor. The decreased number of alpha3 nAChRs in UC compared with controls may be related to an increased cell turnover in UC.

Administration, Cutaneous↗

PubMed2002

Milk production and economic measures in confinement or pasture systems using seasonally calved Holstein and Jersey cows.

This 4-yr study examined total lactation performance of dairy cows in two feeding systems: pasture-based and confinement. Spring and fall calving herds were used and each seasonal herd had 36 cows on pasture and 36 cows in confinement with 282 Holstein and 222 Jersey cows included over seven seasonal replicates. Pasture-fed cows received variable amounts of grain and baled haylage depending upon pasture availability. Confinement cows received a total mixed ration with corn silage as the primary forage. Data were collected on milk production, feed costs, and other costs. Pasture-fed cows produced 11.1% less milk than confinement cows. Across treatments, Jerseys produced 23.3% less milk than Holsteins, but calving season and various interactions were not significant. Feed costs averaged $0.95/cow per day lower for pastured cows than confinement cows. Feed costs were lower for Jerseys than Holsteins and for cows calving in spring. Income over feed costs averaged $7.05 +/- 0.34 for confinement Holsteins, $6.89 +/- 0.34 for pastured Holsteins, $5.68 +/- 0.34 for confinement Jerseys, and $5.36 +/- 0.34 for pastured Jerseys; effects of breed were significant but treatment, season, and interactions were not. Economic factors such as labor for animal care, manure handling, forage management, and cow culling rates favored pastured cows. Higher fertility and lower mastitis among Jerseys partially offsets lower income over feed cost compared with Holsteins. Milk production was lower in this study for pasture-based systems but lower feed costs, lower culling costs, and other economic factors indicate that pasture-based systems can be competitive with confinement systems.

Animal Feed↗

PubMed2002

Reproduction, mastitis, and body condition of seasonally calved Holstein and Jersey cows in confinement or pasture systems.

Dairy cows in confinement and pasture-based feeding systems were compared across four spring-calving and three fall-calving replicates for differences in reproduction, mastitis, body weights, and body condition scores. Feeding systems and replicates included both Jersey and Holstein cows. Cows in confinement were fed a total mixed ration, and cows on pasture were supplemented with concentrates and provided baled hay or haylage when pasture supply was limiting. Breeding periods were for 75 d in spring or fall. Reproductive performance did not differ significantly due to feeding system or season. Jerseys had higher conception rates (59.6 vs. 49.5 +/- 3.3%) and higher percentages of cows pregnant in 75 d (78.1 vs. 57.9 +/- 3.9%) than Holsteins. Cows in confinement had 1.8 times more clinical mastitis and eight times the rate of culling for mastitis than did cows on pasture. Jerseys had half as many clinical cases of mastitis per cow as Holsteins. Only 41 +/- 5% of confinement Holsteins remained for a subsequent lactation, starting within the defined calving season compared with 51 +/- 5% of pastured Holsteins and 71 and 72 +/- 5% of Jerseys, respectively. Body weights and condition scores were generally higher for confinement cows than pastured cows, and Jerseys had higher condition scores and lower body weights than Holsteins. In summary, pastured cows had fewer clinical cases of mastitis, lower body condition scores, and lower body weights than confinement cows. Holsteins were less likely to rebreed, had more mastitis, higher culling rates, and lower body condition scores than Jerseys.

Animal Feed↗

PubMed2001

Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced. AIM: To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel. METHODS: The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks. RESULTS: Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores. CONCLUSIONS: Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.

Administration, Oral↗

PubMed2001

Megacystis-microcolon-intestinal hypoperistalsis syndrome and the absence of the alpha3 nicotinic acetylcholine receptor subunit.

BACKGROUND & AIMS: The megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare disease of childhood that presents early with intestinal hypoperistalsis, hydronephrosis, and hydroureters. Transgenic mice that lack the alpha3 subunit containing nicotinic acetylcholine (nAChR) have a phenotype similar to that of MMIHS. METHODS: We examined the expression of this subunit in control and MMIHS tissue derived from patients using in situ hybridization (ISH) and immunocytochemistry (ICC). RESULTS: In controls, both techniques showed a wide distribution of alpha3 nAChRs present in ganglion cells, muscle, and epithelium. By contrast, most MMIHS tissue gave negative staining with ISH and variable results with ICC. CONCLUSIONS: These observations are consistent with a lack of alpha3 nAChRs contributing to the pathogenesis of MMIHS.

Abnormalities, Multiple↗

PubMed2001

Comparison of fatty acid content of milk from Jersey and Holstein cows consuming pasture or a total mixed ration.

Holstein (n = 19) and Jersey (n = 18) cows were used to study effects of two feeding systems on fatty acid composition of milk. Confinement cows were fed a total mixed ration with corn silage and alfalfa silage and pastured cows grazed a crabgrass (90%) and clover (10%) pasture and were allowed 5.5 kg of grain per head daily. Two milk samples were collected from each cow at morning and afternoon milkings 1 d each week for four consecutive weeks in June and July 1998. One set of milk samples was analyzed to determine fatty acid composition, and the second set was used for crude protein and total fat analyses. Data were analyzed by the general linear models procedure of SAS, using a split-plot model with breed, treatment, and breed x treatment as main effects and time of sampling and week as subplot effects along with appropriate interactions. Milk from pastured cows was higher than milk from confinement cows for the cis-9, trans-11 octadecadienoic acid isomer of conjugated linoleic acid (CLA). Also, milk from Holsteins was higher than milk from Jerseys for C16:1, C18:1, and CLA and lower than Jerseys for C6:0, C8:0, C10:0, C12:0, and C14:0. Several treatment x week interactions existed, but main effects were still important; for example, proportions of CLA in milk of grazed cows were relatively constant across weeks (0.66, 0.64, 0.64, and 0.69% +/- 0.02%, respectively), but the CLA in milk of confinement cows increased in wk 4 (0.35, 0.31, 0.31, and 0.48% +/- 0.02% for wk 1 to 4, respectively). There are potentially important differences in fatty acid composition of milk from cows consuming a warm season pasture species compared with milk from cows consuming a total mixed ration, as well as differences between Holstein and Jersey breeds.

Animal Feed↗

PubMed2000

Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries.

OBJECTIVES: [corrected] We investigated which nerve pathways are necessary to achieve ejaculation using penile vibratory stimulation (PVS) in men with spinal cord injury (SCI). METHODS: Eight men with SCI were selected based on the presence of a bulbocavernosus reflex (BCR) and consistent antegrade ejaculation with PVS. Level of injury was cervical (4), upper thoracic (4), and lower thoracic (1). Mean age was 30.4 years (range 22 to 38). Usual responses to PVS included autonomic dysreflexia (4), erection (4), and consistent somatic responses such as abdominal contractions (8). Local anesthesia of the dorsal penile nerves (penile block) was achieved using 1% plain lidocaine injection. Effective penile block was confirmed by loss of the BCR. Two PVS ejaculation trials were performed: one trial during the penile block and one trial when the penile block had worn off. In 4 subjects, the bladder contents were analyzed for retrograde ejaculation. RESULTS: With the penile block, ejaculation was inhibited in 100% of the subjects. None of the bladder washings demonstrated sperm, indicating absence of retrograde ejaculation. None of the subjects exhibited their usual erectile response, somatic responses, or signs of autonomic dysreflexia. After the penile block wore off, PVS induced ejaculation in all subjects. If subjects usually had erection, somatic responses, or signs of autonomic dysreflexia, these also returned. CONCLUSIONS: Our data suggest that ejaculatory response to PVS in SCI men requires the presence of intact dorsal penile nerves.

Ejaculation↗

PubMed2000

Evaluation of behavioral disinhibition in P/NP and HAD1/LAD1 rats.

1. Two lines of rats specifically bred for alcohol preference were exposed to two different behavioral tasks that required behavioral inhibition to successfully solve. 2. Learning and performance of a step-down passive avoidance task and a differential reinforcement of low-rate responding task were studied in P/NP and HAD1/LAD1 rats. 3. While the P rats had difficulty in learning both tasks, HAD1, LAD1 and NP rats performed at control levels. 4. These data suggest that P rats, but not HAD1 rats, may have problems learning tasks that require inhibition of ongoing or previously learned behaviors.

Animals↗

PubMed2000

Eyeblink classical conditioning: hippocampal formation is for neutral stimulus associations as cerebellum is for association-response.

Extensive evidence has been amassed that the cerebellum, hippocampus, and associated circuitry are activated during classical conditioning of the nictitating membrane/eyeblink response. In this article, the authors argue that the cerebellum is essential to all eyeblink classical conditioning paradigms. In addition, the septohippocampal system plays a critical role when the classical conditioning paradigm requires the formation of associations in addition to the simple association between the conditioned and unconditioned stimuli. When only a simple conditioned stimulus--unconditioned stimulus association is needed, the septohippocampal system has a more limited, modulatory role. The neutral stimulus association versus simple association-response distinction is one of the ways in which declarative or relational memory can be separated from nondeclarative or nonrelational memory in classical conditioning paradigms.

Blinking↗

PubMed2000

Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis.

BACKGROUND: Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit. AIMS: To examine the in vitro effect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator. METHODS: Nicotine, 1-10 microM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetase inhibitor, was added before nicotine was administered again. RESULTS: Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction. CONCLUSIONS: Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide-this appears to be 'up-regulated' in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.

Adult↗

PubMed2000

Role of smoking in inflammatory bowel disease: implications for therapy.

The relationship between smoking and inflammatory bowel disease is now firmly established but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohn's disease. These differences have been the subject of much interest and scrutiny with the hope that they may offer some insight into the pathogenesis of the two conditions and possibly lead to alternative therapeutic options. Nicotine is probably the principal active ingredient in smoking responsible for the association; trials have shown it to be of some benefit in ulcerative colitis, but further research is required to establish its therapeutic role, and the relevant mechanisms responsible for its action. In this article, we review the role of smoking in inflammatory bowel disease and its implication for therapy.

Colitis, Ulcerative↗

PubMed2000

Impairment in eyeblink classical conditioning in adult rats exposed to ethanol as neonates.

BACKGROUND: Eyeblink classical conditioning is a learning task that engages well-defined neural circuitry in the cerebellum and brainstem. Binge-like exposure to alcohol during the neonatal brain growth spurt in rats produces neurotoxic effects on both the cerebellum and the brainstem. The precise localization of the neural substrates of eyeblink conditioning makes it an ideal task to study functional disruptions in the cerebellum and brainstem caused by early exposure to alcohol. The purpose of this study was to determine whether impairments in eyeblink conditioning caused by neonatal binge exposure to alcohol persist into adulthood, indicative of long-lasting abnormalities in cerebellar and brainstem function. METHODS: Group Ethanol received alcohol doses of 5.25 g/kg/day via intragastric intubation on postnatal days 4-9. Group Sham Intubated underwent the intragastric intubation procedures on postnatal days 4-9 but did not receive any infusions. Group Nonintubated did not receive any intubations. When all rats were at least 3 months old, they were tested in either paired or unpaired eyeblink conditioning. RESULTS: Group Ethanol showed impaired eyeblink conditioning and some abnormalities in conditioned response timing. Control groups did not differ from each other. CONCLUSIONS: The present data indicate that early exposure to alcohol has long-term effects on eyeblink conditioning, perhaps through enduring effects associated with alcohol-induced loss of Purkinje cells of the cerebellum.

Animals↗

PubMed1999

An oral formulation of nicotine for release and absorption in the colon: its development and pharmacokinetics.

AIMS: Ulcerative colitis is predominantly a disease of nonsmokers and transdermal nicotine has therapeutic value in active disease; however side-effects are troublesome. The aim of this study was to develop an oral formulation of nicotine which would be slowly released in the colon over 6 h, and to examine its pharmacokinetic profile in 12 healthy volunteers, with measurements of serum nicotine and cotinine, its principal metabolite. METHODS: Nicotine was combined with a polyacrylic carbomer, Carbopol 974P which was incorporated into 13 different vehicles and their release profiles examined in vitro. The polyglycolized glyceride, Gelucire 50/13, was chosen for subsequent kinetic studies because it consistently produced a suitable release pattern which was linear. Capsules containing 3 mg nicotine, combined with carbomer in Gelucire 50/13, were coated with an acrylic resin Eudragit L; this ensured the capsule would remain intact until the ileum. On 2 separate days, 6 and 15 mg nicotine, contained in 2 and 5 capsules, respectively, were administered to 12 subjects, all nonsmokers, mean age 28 years. Serial blood measurements were taken for 36 h, serum nicotine and cotinine concentrations were measured by gas liquid chromatography. RESULTS: There was considerable intersubject variability in the nicotine and cotinine values. Plasma nicotine levels began to rise about 4 h after ingestion of the capsules, corresponding with the oro-caecal transit time. Cmax nicotine values were 2.2 and 5 ng ml-1, obtained 7 h after the ingestion of 6 and 15 mg, respectively, of the formulation. The corresponding Cmax values for cotinine were 37 and 94.4 ng ml-1, occurring after 9-10 h. The mean for elimination half-lives in the 24 studies, including the 6 and 15 mg doses, for nicotine were 4.3+/-2.7 h and for cotinine 16.8+/-7.5 h. With 6 mg nicotine-carbomer, only 1 of 12 volunteers had possible side-effects, but with the 15 mg dose 11 out of the 12 reported adverse effects which were systemic or gastrointestinal in nature-their timing corresponded with peak serum concentrations of nicotine. CONCLUSIONS: An oral formulation of nicotine has been developed; in the ileum and colon, this becomes available for slow linear release over 6 h and delivers high concentrations of nicotine for topical effect on the colon. 6 mg Nicotine was well tolerated, whilst 15 mg gave both systemic and gastrointestinal side-effects. High concentrations of topical nicotine in the colon are achieved with relatively low systemic bioavailablity-reflected by the Cmax and AUC values for nicotine. This, or comparable formulations, may be of therapeutic value in ulcerative colitis.

Absorption↗