A by-product of swine slaughtering as a protein source in broiler diets: effects on performance, composition of excreta, litter quality and on foot pad health.

Foot pad dermatitis (FPD) is of great concern in poultry industry, and dietary strategies are needed to improve foot pad health because of animal welfare and economic reasons. As the main factor for the development of FPD is the DM content of litter (consisting mainly of excreta; Kamphues et al., 2011), there are different dietary approaches to influence this disease pattern. In two consecutive trials, a total of 200 broilers were kept from day 7 until the 35th day of life. They were divided into four groups at each trial and fed with one of four experimental diets, based on wheat and corn mainly, but differing in the protein source: Group 1 was fed a diet with soya bean meal (SBM) as the main protein source, whereas Group 2, Group 3 and Group 4 were assigned to diets with 4, 8 and 12% of a protein-rich (66.7% CP in DM) by-product of swine slaughtering [Swine Protein Meal (SPM); in exchange for SBM]. The inclusion of 12% SPM resulted in a decreased dietary potassium content of about 3 g/kg diet (Group 1 vs. 4). Increasing dietary levels of the by-product (8 and 12%) led to lowered feed intake (Group 1 vs. 4: ~10%) and weight gain (Group 1 vs. Group 4: ~8.5%). Although highest DM contents of excreta and litter were determined in Group 4, foot pad health was not influenced positively as hypothesized. Remarkable was the observed 'stickiness' of excreta when the by-product was included in the diet at increasing levels, presumably due to the high proportion of bones in the by-product. In conclusion, substituting SBM by 4% of the by-product of swine slaughtering in broiler diets did not impair performance parameters, but led to the most favourable foot pad scores in this study.

Use of biomarkers or echocardiography in pulmonary embolism: the Swiss Venous Thromboembolism Registry.

BACKGROUND: Cardiac biomarkers and echocardiography for assessing right ventricular function are recommended to risk stratify patients with acute non-massive pulmonary embolism (PE), but it remains unclear if these tests are performed systematically in daily practice. DESIGN AND METHODS: Overall, 587 patients with acute non-massive PE from 18 hospitals were enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER): 178 (30%) neither had a biomarker test nor an echocardiographic evaluation, 196 (34%) had a biomarker test only, 47 (8%) had an echocardiogram only and 166 (28%) had both tests. RESULTS: Among the 409 (70%) patients with biomarkers or echocardiography, 210 (51%) had at least one positive test and 67 (16%) had positive biomarkers and right ventricular dysfunction. The ICU admission rates were 5.1% without vs. 5.6% with testing (P = 0.78), and thrombolysis or embolectomy were performed in 2.8% vs. 4.9%, respectively (P = 0.25). In multivariate analysis, syncope [odds ratio (OR): 3.49, 95% confidence interval (CI): 1.20-10.15; P = 0.022], tachycardia (OR: 2.31, 95% CI: 1.37-3.91; P = 0.002) and increasing age (OR: 1.02; 95% CI: 1.01-1.04; P < 0.001) were associated with testing of cardiac risk; outpatient status at the time of PE diagnosis (OR: 2.24, 95% CI: 1.49-3.36; P < 0.001), cancer (OR: 1.81, 95% CI: 1.17-2.79; P = 0.008) and provoked PE (OR: 1.58, 95% CI: 1.05-2.40; P = 0.029) were associated with its absence. CONCLUSION: Although elderly patients and those with clinically severe PE were more likely to receive a biomarker test or an echocardiogram, these tools were used in only two-thirds of the patients with acute non-massive PE and rarely in combination.

PROMAXX inhaled insulin: safe and efficacious administration with a commercially available dry powder inhaler.

OBJECTIVES: We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) properties of recombinant human insulin inhalation powder (RHIIP), manufactured with PROMAXX technology, which allows formation of uniform protein microspheres. METHODS: Thirty healthy male subjects [age 30 +/- 1 years (mean +/- s.e.), body mass index 24.2 +/- 0.3 kg/m(2)] in a randomized crossover study received 10 IU subcutaneous regular human insulin (SCIns) and 6.5 mg of RHIIP [187 IU, Cyclohaler dry powder inhaler (DPI)] under euglycaemic glucose clamp conditions. Subjects were trained to inhale RHIIP with a flow rate of 90 +/- 30 l/min prior to dosing. RESULTS: Inhalation of RHIIP was well tolerated with no episode of cough or shortness of breath. RHIIP showed a faster onset of action than SCIns [time to reach 10% of total area under the glucose infusion rate (GIR) curves 73 +/- 2 vs. 95 +/- 3 min, time to maximal metabolic effect (T(max)GIR) 173 +/- 13 vs. 218 +/- 9 min, both p < 0.0001]. Duration of action (371 +/- 11 vs. 366 +/- 7 min) and total metabolic effect (AUCGIR0-10 h 2734 +/- 274 vs. 2482 +/- 155 mg/kg) were comparable. PK results were in accordance with the PD findings. Relative bioavailability (BA) of RHIIP was 12 +/- 2%, and relative biopotency (BP) was 6 +/- 1%. CONCLUSIONS: PROMAXX technology allowed for safe and efficacious administration of RHIIP to the deep lung with an off-the-shelf DPI. RHIIP showed a fast onset of action and BA/BP comparable to that reported for other inhaled insulin formulations using specifically designed inhalers. Improvements in the insulin delivery technique might allow to optimize drug application in all cases with even higher BA/BP with RHIIP.

Successful management of claustrophobia and depression during allogeneic SCT.

As psychological problems are frequent in SCT patients we report on a patient with chronic myeloid leukemia, claustrophobia and depression. The successful allogeneic stem cell transplant of this patient in a reverse isolation setting required intensive interdisciplinary hematological, psychological and psychiatric collaboration. Psychopharmacologically the patient was treated with lorazepam 1 mg at 10 a.m. and 8 p.m. and after crisis on day +6, and 2.5 mg twice daily i.v. until one day before discharge (total 20 doses). Psychological counseling followed a cognitive-behavioural approach including progressive muscle relaxation and cognitive techniques focusing on the actual coping processes.

Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults.

BACKGROUND: Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, both types of medications are associated with side effects that can limit their usefulness in the outpatient setting. OBJECTIVE: Two studies with identical protocols assessed the single- and multiple-dose analgesic efficacy and tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the treatment of acute pain after orthopedic surgery. METHODS: These were multicenter, randomized, placebo- and active-controlled, double-blind, parallel-group trials conducted between January and June 1998. Both consisted of a single-dose assessment period (SDAP) and a multiple-dose assessment period (MDAP). In the SDAP, patients who had undergone orthopedic surgery received a single oral dose of celecoxib 200 mg, hydrocodone 10 mg/acetaminophen 1000 mg, or placebo within 24 hours after the end of anesthesia, with pain assessments conducted over the following 8-hour period. In the MDAP, extending from 8 hours after the first dose of study medication up to 5 days, patients who had received < or =1 dose of rescue medication during the SDAP continued on study medication (placebo recipients were rerandomized to active treatment), which could be taken up to 3 times a day as needed. RESULTS: A total of 418 patients were enrolled in the 2 trials. During the SDAP, 141 patients received celecoxib, 136 received hydrocodone/acetaminophen, and 141 received placebo. During the MDAP, 185 patients received celecoxib and 181 received hydrocodone/acetaminophen. When the combined data were analyzed, mean pain intensity difference (PID) scores generally favored the active treatments over placebo from 1 to 6 hours (with the exception of 1.5 hours) after dosing (P < or = 0.016) and favored celecoxib over the other treatments at 7 and 8 hours after dosing (P < 0.001). The active treatments demonstrated superior summed PID scores through 8 hours (P < 0.001), significantly shorter median times to onset of analgesia (P < 0.05), and significantly longer median times to first use of rescue medication (P < 0.05). During the MDAP, more hydrocodone/acetaminophen-treated patients (20%) than celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the celecoxib group had significantly lower maximum pain intensity scores (P < 0.001, days 2-5), required fewer doses of study medication (P < or = 0.01, days 3-5), and had superior scores on a modified American Pain Society Patient Outcome Questionnaire (P < or = 0.013). In addition, a significantly lower proportion of celecoxib-treated patients experienced adverse events (43%) compared with hydrocodone/acetaminophen-treated patients (89%; P < 0.001). CONCLUSIONS: Over 8 hours, patients with moderate to severe pain after orthopedic surgery experienced comparable analgesia with single doses of celecoxib and hydrocodone/acetaminophen. Over a 5-day period, oral doses of celecoxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerability compared with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day. Most patients required no more than 2 daily doses of celecoxib 200 mg for the control of their postorthopedic surgical pain.

ICV administration of CRF blocker (CRF9-41 delta helical) reduces morphine withdrawal in rats.

1. The effects of CRF9-41 delta helical on morphine withdrawal signs in rats were studied. 2. Intracerebroventricular administration of CRF9-41 delta helical 5 at 10 micrograms/kg reduced central and peripheral symptoms of the withdrawal syndrome, such as ptosis, jumping, wet dog shakes and teeth chattering; other signs remained unchanged. The effect were not dose dependent. 3. The hypothermi characteristic of the Withdrawal syndrome was reduced by CRF9-41 delta helical. 4. These results suggest that the hypothalamo pituitary adrenal(HPA) axis play an important role in the morphine withdrawal syndrome in rats.

[Double-blind comparative study of the effectiveness and tolerance of 900 mg dexibuprofen and 150 mg diclofenac sodium in patients with painful gonarthrosis]. / Doppelblinde Studie zum Vergleich der Wirksamkeit und Verträglichkeit von 900 mg Dexibuprofen und 150 mg Diclofenac-Natrium bei Patienten mit schmerzhafter Gonarthrose.

In this randomized double-blind, parallel-group study the efficacy of 300 mg oral dexibuprofen three times daily and 50 mg oral diclofenac sodium three times daily was tested for equivalence in 110 patients with painful osteoarthritis of the knee. During the 15-day treatment period the functional index for knee osteoarthritis according to Lequesne was improved under dexibuprofen by a mean of 7.4 and by a mean of 7.3 under treatment with diclofenac sodium. The test for equivalence by one-sided Wilcoxon-Mann-Whitney test shows equivalent efficacy of dexibuprofen by a Mann-Whitney-statistic of 0.505 and 0.415 as its lower boundary of the 95% confidence interval. The descriptive analysis of secondary criteria such as intensity of pain, rest pain, pain at beginning, nocturnal pain, tenderness, restriction of movement, handicap, subjective estimation of disease progression, as well as global judgement of efficacy and tolerance by investigator and patient confirm equivalence of both preparations. The pooled analysis of all parameters, tolerability included, by a Mann-Whitney-statistic of 0.520 with the lower boundary of the 95% confidence interval of 0.467 shows equivalence of both drugs with a trend to superiority of dexibuprofen due to its better tolerability. 7.3% of the patients on dexibuprofen and 14.5% of the patients on diclofenac sodium dropped out because of side-effects.

Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group.

OBJECTIVE: To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania. DESIGN: Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness. PATIENTS: A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals. INTERVENTIONS: After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 mumol/L (150 micrograms/mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively. MAIN OUTCOME MEASURES: Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia. RESULTS: Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P = .017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P = .004) and 49% for lithium (P = .025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients. CONCLUSIONS: Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium.

[Speed of intubation using a new neuromuscular blocker. Rocuronium bromide (ORG 9426)]. / Rapidez de intubación de un nuevo bloqueador neuromuscular. Bromuro de rocuronio (ORG 9426).

OBJECTIVES: To compare intubation conditions and neuromuscular parameters, patency time, maximum level of block, time and clinical duration of effect for rocuronium bromide 0.6 mg/kg (ORG 9426) versus equally potent doses of vecuronium and atracurium under similar experimental conditions. PATIENTS AND METHODS: Sixty patients were divided into three groups of twenty. Intubation conditions were scored on a scale of 3-12 points based on relaxation of the vocal cords, presence of cough and ease of laryngoscopy after 60 or 90 sec. Neuromuscular parameters were obtained by integrated electromyography of the thenar and hypothenar muscle structure, evoked by supramaximal stimuli of the cubital nerve in train of four (2 Hz in 2 sec). The shape of the electrocardiographic curve, heart rate and mean arterial pressure measured non-invasively were recorded throughout the surgical procedure. RESULTS: Means of onset times and times of effect for rocuronium (33 and 135 sec) were significantly lower than those obtained with vecuronium and atracurium. Clinical duration, free of hemodynamic changes, was similar in the three groups. Rocuronium produces excellent intubation conditions 60 sec after administration, although at this point peripheral muscle block was only partial. Rocuronium may be superior to other neuromuscular blockers available today as a result of the speed with which it affords excellent intubation conditions.

Pharmacokinetics and pharmacodynamics of rocuronium bromide in adult patients.

In seven patients (M/F: 4:3) rocuronium 0.6 mg kg-1 was given after the induction of anaesthesia with propofol, and during maintenance with N2O/O2, halothane 0.5% and alfentanil 60-90 micrograms kg-1 h-1. Intubation conditions were scored at 60 s and lag time, onset time, maximal block achieved, recovery to 25% of T1, and Recovery Index, were measured using a Relaxograph. Blood samples were taken over a 300 min period and analysed for rocuronium. Intubating conditions at 60 s were excellent in all patients. Mean clearance was 5.2 ml kg-1 min-1, the terminal half-life was 69 min and distribution volume at steady state was 0.22 litre kg-1. Cumulative urinary excretion was around 18% within 24 h.

[Difficulties of animal experiments in psychopharmacology. Punctual aspects of antidepressants]. / Dificultades que plantea la experimentación animal en psicofarmacología. Aspectos puntuales de los antidepresivos.

Animal psychopharmacological experimentation encounters great difficulty due to the lack of animal models for reproducing mental illness. This results from the greatly complex fashion of CNS, the lack of knowledge of biochemical and/or anatomical substrates of psychiatric pathology, and the difficulty in placing some CNS functions, such as memory and vice versa. The application of selective neurotoxins capable of specifically destroying a neuronal nucleus allows to advance in the knowledge of the CNS functions. Some easy experimental methods allow a quick investigation of certain pharmacological effects on CNS, though they have to be completed with more complex models. It is difficult to investigate the possible antidepressant effect because it is related to different mechanisms of action, it has an onset delay, and some trials which are positive to some drug with no antidepressant effect. In turn they have no right answer to other drugs with confirmed clinical efficacy. The forced swimming pool test that appears to be the most convenient for researching the possible antidepressant effect has been studied, although it should be completed with a spontaneous motility test.

Tulobuterol: a full beta-adrenoceptor agonist or a partial beta-agonist with membrane stabilizing activity?

1. The effects of tulobuterol on the atrial rate was compared with those of isoproterenol, pindolol and propranolol in spontaneously beating isolated right atria of the rat. 2. Isoproterenol markedly increased atrial rate. To the contrary, propranolol, pindolol and tulobuterol decreased atrial frequency. The chronotropic effect of tulobuterol was similar to that of pindolol but lower than that of propranolol. 3. Interactions between tulobuterol and isoproterenol showed that tulobuterol potentiated the chronotropic effect of low concentrations of isoproterenol but reduced the positive chronotropic response to higher concentrations of isoproterenol. 4. These results suggest that tulobuterol is a partial agonist on atrial beta-receptor but also seems to have another action (possibly a membrane stabilizing activity) which reduced the originally induced effect on beta-receptors as a non-competitive antagonist.

Mechanism of action of B-HT 933 (azepexole) in rat vas deferens and guinea-pig ileum.

The mechanism of action of B-HT 933 (azepexole) was studied on the rat vas deferens and myenteric plexus-longitudinal muscle (MP-LM) of the guinea-pig ileum. The drug caused a concentration-dependent inhibition of the twitch response in both preparations. The maximal inhibition in both preparations was 80-90%. B-HT 933 did not affect the cumulative dose-response curves of the vas deferens and of MP-LM to noradrenaline (NA) and acetylcholine (Ach) respectively. Yohimbine antagonized in a competitive way the twitch inhibitory effect of B-HT 933 on vas deferens and on MP-LM; the pA2 values were 8.62 and 8.5, respectively. The twitch inhibitory effects of B-HT 933 were not antagonized by propranolol. The results suggest that the action of B-HT 933 is mediated by stimulation of presynaptic alpha 2-receptors.

Effects of chronic treatment with atypical neuroleptics on the biosynthesis and release of opioid peptides in guinea-pig ileum.

The guinea-pig ileum myenteric plexus is known to contain opioid peptides, which can be released by electric stimulation at high frequency. Haloperidol, a classic neuroleptic drug, increases the biosynthesis and release of endogenous opioid peptides from the myenteric plexus. In the present work we have examined the effects of chronic treatment with sulpiride and clozapine, two atypical neuroleptics, on the release of these peptides in the myenteric plexus of guinea-pig ileum. Both neuroleptics, administered over a period of 7 days, produced an increase of the inhibitory response obtained by electrical stimulation at 10 Hz of the ileum myenteric plexus-longitudinal muscle preparation. The inhibitory response was reversed by the specific opioid antagonist naloxone, which suggest that the increase in the inhibitory response produced by blocking the dopaminergic receptors is mediated by an increase in the release of opioid peptides. When sulpiride- or clozapine-treated guinea-pigs received cycloheximide (an inhibitor of peptide biosynthesis) there was a significant decrease of the inhibitory response, which indicates that neuroleptics produced an increase of the synthesis of opioid peptides in the ileum myenteric plexus. These results reveal a possible influence of the dopaminergic system on the biological turnover of these peptides.

The beta-agonist drug tulobuterol decreases cardiac automaticity in the rat: comparison with isoproterenol.

The effect of the new beta-agonist drug tulobuterol, has been compared with isoproterenol in an experimental model of ectopic cardiac automaticity induced by local injury in the isolated right ventricle of the rat. Isoproterenol significantly increases ventricular automaticity even with the lowest concentrations tested (10(-9)M). Tulobuterol, at concentrations ranging from 10(-9)M to 10(-6)M do not induce any change on the automatic ventricular frequency. Nevertheless, at higher concentrations (10(-5) and 5 X 10(-5)M), tulobuterol decreases the experimentally induced ventricular automaticity. Our results suggest that the new beta-agonist drug tulobuterol does not increase ventricular automaticity but, in fact, decreases it.

Quantitative study on the uterus-inhibiting activity of sodium naproxen in rat isolated uterus.

Action of Sodium Naproxen on spontaneous and field stimulated motility of isolated rat uterus was studied. Sodium Naproxen inhibited both spontaneous and field stimulated motility. The IC50 on spontaneous motility was lower than the IC50 on stimulated motility. The inhibition produced on the field stimulated uterus was more regular in relationship to concentration used of Sodium Naproxen. The IC50 of Sodium Naproxen in these experimental conditions was 8.22 X 10(-4) M (pD2 = 3.09 +/- 0.02) and the maximum inhibitory effect was 100%. These results show that prostaglandin synthesis plays a necessary role in uterine contraction, spontaneous or induced by field stimulus.