ACTH reduces the rise in ApoB-48 levels after fat intake

It has been repeatedly demonstrated that ACTH administration lowers plasma lipid concentrations in man. The present study was designed to test the hypothesis, based on observations of decreased apolipoprotein B (ApoB) synthesis and secretion in vitro, that ACTH administration inhibits the postprandial output of ApoB in man. Therefore, we studied the response to a fat-rich meal supplemented with Vitamin A in eight healthy volunteers, who underwent this test without premedication, after 4 days administration of ACTH, and after 4 days administration of a glucocorticoid (betamethasone). As expected, fasting plasma levels of low-density lipoproteins (LDL)-cholesterot (-25%) and ApoB (-17%) decreased after ACTH, but not after betamethasone administration. Also, the elevation of plasma ApoB-48 in response to fat intake (to twice the basal levels) was markedly reduced after ACTH administration. However, the postprandial rise in plasma triglycerides and retinyl palmitate was unimpaired, suggesting that ACTH administration induced the secretion of fewer but larger chylomicrons. The effect of betamethasone on the postprandial response was similar but less pronounced. This study confirms earlier reports on the lipid-lowering effects of ACTH and supports our theory, based on in vitro studies, that the lipid-lowering effects of ACTH administration in man involves an inhibition of ApoB production. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

G protein ss gamma subunits mediate presynaptic inhibition of transmitter release from rat superior cervical ganglion neurones in culture

The activation of presynaptic G protein-coupled receptors (GPCRs) is widely reported to inhibit transmitter release; however, the lack of accessibility of many presynaptic terminals has limited direct analysis of signalling mediators. We studied GPCR-mediated inhibition of fast cholinergic transmission between superior cervical ganglion neurones (SCGNs) in culture. The adrenoceptor agonist noradrenaline (NA) caused a dose-related reduction in evoked excitatory postsynaptic potentials (EPSPs). NA-induced EPSP decrease was accompanied by effects on the presynaptic action potential (AP), reducing AP duration and amplitude of the after-hyperpolarization (AHP), without affecting the pre- and postsynaptic membrane potential. All effects of NA were blocked by yohimbine and synaptic transmission was reduced by clonidine, consistent with an action at presynaptic alpha 2-adrenoceptors. NA-induced inhibition of transmission was sensitive to pre-incubation of SCGNs with pertussis toxin (PTX), implicating the involvement of G alpha(i)/(o)beta y subunits. Expression of G alpha transducin, an agent which sequesters G protein beta gamma (G beta y) subunits, in the presynaptic neurone caused a time-dependent attenuation of NA-induced inhibition. Injection of purified G beta gamma subunits into the presynaptic neurone inhibited transmission, and also reduced the AHP amplitude. Furthermore, NA-induced inhibition was occluded by pre-injection of G beta gamma subunits. The Ca2+ channel blocker Cd2+ mimicked NA effects on transmitter release. Cd2+, NA and G beta gamma subunits also inhibited somatic Ca2+ current. In contrast to effects on AP-evoked transmitter release, NA had no clear action on AP-independent EPSPs induced by hypertonic solutions. These results demonstrate that G beta gamma subunits functionally mediate inhibition of transmitter release by alpha 2-adrenoceptors and represent important regulators of synaptic transmission at mammalian presynaptic terminals.

Determinants of Accelerated Small Intestinal Transit in Alcohol-Related Chronic Pancreatitis

Patients with chronic pancreatitis may have abnormal gastrointestinal transit, but the factors underlying these abnormalities are poorly understood. Gastrointestinal transit was assessed, in 40 male outpatients with alcohol-related chronic pancreatitis and 18 controls, by scintigraphy after a liquid meal labeled with (99m)technetium-phytate. Blood and urinary glucose, fecal fat excretion, nutritional status, and cardiovascular autonomic function were determined in all patients. The influence of diabetes mellitus, malabsorption, malnutrition, and autonomic neuropathy on abnormal gastrointestinal transit was assessed by univariate analysis and Bayesian multiple regression analysis. Accelerated gastrointestinal transit was found in 11 patients who showed abnormally rapid arrival of the meal marker to the cecum. Univariate and Bayesian analysis showed that diabetes mellitus and autonomic neuropathy had significant influences on rapid transit, which was not associated with either malabsorption or malnutrition. In conclusion, rapid gastrointestinal transit in patients with alcohol-related chronic pancreatitis is related to diabetes mellitus and autonomic neuropathy.

A randomized controlled trial of buprenorphine in the management of short-term ambulatory heroin withdrawal

Aim: To determine whether buprenorphine is more effective than clondine and other symptomatic medications in managing ambulatory heroin withdrawal.
Design: Open label. prospective randomized controlled trial examining
withdrawal and 4-week postwithdrawal outcomes on intention-to-treat.
Setting: Two specialist, out-patient drug treatment centres in inner city
Melbourne and Sydney, Australia.
Participants: One hundred and fourteen dependent heroin users were recruited. Participants were 18 yea rs or over. and with no significant other drug dependence, medical or psychiatric conditions or recent methadone treatment. One hundred and one (89%) participants completed a day 8 research interview examining withdrawal outcomes, and 92 (81%) completed day 35 research interview examining postwithdrawal outcomes.
Interventions: Participants randomized to control (n = 56) (up to 8 days or
clonidine and other symptomatic medications) or experimental (n = 58) (up to 5 days of buprenorphine) withdrawal groups. Following the 8-day withdrawal episode, participants could self-select from range of postwithdrawal options (naltrexone, substitution maintenance or counselling).
Measurements: Retention in withdrawal: heroin use during withdrawl: and
retention in drug treatment 4 weeks after withdrawal.
Secondary outcomes: Withdrawal severity: adverse events, and heroin use in the postwithdrawal period.
Findings: The experimental group had better treatment retention at day 8 (86% versus 57%, P = 0.001, 95% CI for numbers needed to treat (NNT) = 3-8) and day 35 (62% versus 39%, P = 0.02, 95% CI for NNT = 4-18): used heroin on fewer days during the withdralwal programlme (2.6 ± 2.5 versus 4.5 ± 2. 3.
P < 0.001. 95% CI = 1- 2.5 days) and in the postwithdrawal period (9.0±8.2
versus 14.6± 10. P<O.Ol. 95% CI = I .8- 9.4): and reported less withdrawal
severity. No severe adverse events reported.
Conclusions: Buprenorphine is effective for short-term ambulatory heroin
withdrawaI, with greater retention, less heroin use and less withdrawal discomfort during withdrawal: and increased postwithdrawal treatment retention than symptomatic medications.

Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study.

The negative symptoms of schizophrenia remain a major clinical challenge. Reboxetine is an antidepressant whose major mechanism of action is as a noradrenergic reuptake inhibitor. This study was a 6-week randomized placebo-controlled trial of reboxetine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The trial failed to demonstrate any significant difference between the placebo and reboxetine groups on any of the outcome measures. This trial does not suggest that increased noradreneregic drive mediated by reuptake inhibition in patients taking dopamine antagonists is of therapeutic value in schizophrenia.

Effects of physical and chemical immobilization on hematologic and biochemical variables in captive brown brocket deer (Mazama gouazoubira)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos comportamental, clínico e analgésico promovidos pela injeção epidural preventiva de morfina, xilazina ou clonidina, em equinos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in ovariohysterectomized dogs

Objective-To evaluate analgesic effects of epidurally administered neostigmine alone or in combination with morphine in dogs after ovariohysterectomy.Animals-40 healthy bitches.Procedures-After acepromazine premedication, anesthesia was induced. Dogs randomly received 1 of the following 4 epidural treatments 30 minutes before ovariohysterectomy (n = 10/group): saline (0.9% NaCl) solution (control), morphine (0.1 mg/kg), neostigmine (10 pg/kg), or morphine-neostigmine (0.1 mg/kg and 10 pg/kg, respectively). Analgesia was assessed for 24 hours after surgery by use of a visual analogue.scale (VAS; scale of 0 to 10) or numeric descriptive scale (NDS; scale of 0 to 24) and by the need for supplemental analgesia (morphine [0.5 mg/kg, IM] administered when VAS was >= 4 or NDS was >= 8).Results-Significantly more control dogs (n = 8) received supplemental analgesia, compared with the number of neostigmine-treated dogs (1); no dogs in the remaining groups received supplemental analgesia. Compared with values for the control dogs, the NDS scores were lower for morphine-neostigmine-treated dogs (from 2 to 6 hours and at 12 hours) and for morphine-treated dogs (all time points). The NDS scores were lower for morphine-treated dogs at 3, 12, and 24 hours, compared with values for neostigmine-treated dogs. The VAS was less sensitive than the NDS for detecting differences among groups.Conclusions and Clinical Relevance-Epidurally administered neostigmine reduced the use of supplemental analgesia after ovariohysterectorny in dogs. However, analgesic effects were less pronounced than for epidurally administered morphine or morphine-neostigmine. Adding neostigmine to epidurally administered morphine did not potentiate opioid-induced analgesia.

Variabilidade da freqüência cardíaca em cães anestesiados com infusão contínua de propofol e sufentanil

Foram avaliados os efeitos do propofol associado ao sufentanil sobre o balanço das atividades simpática e parassimpática do coração, investigando-se um possível efeito dose dependente do opióide. Analisou-se a variabilidade da freqüência cardíaca (VFC) de 12 cães adultos pré-medicados com maleato de acepromazina e anestesiados com propofol e três doses diferentes de sufentanil, que variou de 0,025 a 0,1µg/kg/min. Registrou-se o eletrocardiograma 15 minutos após a medicação pré-anestésica e 15, 30, 60, 90 e 120 minutos após a indução anestésica. A VFC foi calculada no domínio da freqüência, mediante análise de 10 intervalos RR consecutivos. Houve redução acentuada da freqüência cardíaca, mas a VFC permaneceu relativamente inalterada.

Safety Assessment of Potentially Inappropriate Medications (PIM) use in Older People and the Factors Associated with Hospital Admission

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da clonidina nas respostas cardiovasculares ao pinçamento aórtico infra-renal: estudo experimental no cão

JUSTIFICATIVA E OBJETIVOS: O pinçamento aórtico infra-renal pode determinar alterações cardiovasculares. A clonidina, um alfa2-agonista, determina bradicardia e diminuição da pressão arterial. O objetivo do estudo foi avaliar os efeitos da clonidina sobre a função cardiovascular, em cães submetidos a pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 16 cães, distribuídos em dois grupos: G Controle - sem a utilização de clonidina e G Clon - clonidina, na dose inicial de 5 µg.kg-1, por via venosa, imediatamente antes do pinçamento aórtico infra-renal, seguido de 2 µg.min-1.m² até o final do estudo. em todos os animais foi realizada ligadura infra-renal da aorta, por 45 minutos. Os atributos hemodinâmicos foram estudados nos momentos C (controle), após 10 (Ao10) e 25 (Ao25) minutos do pinçamento aórtico, e após 10 (DAo10) e 25 (DAo25) minutos do despinçamento aórtico. RESULTADOS: Durante o pinçamento aórtico, houve diferença significante entre os grupos, em relação à freqüência cardíaca, pressão arterial média e índice cardíaco (G Controle > G Clon). Após o despinçamento aórtico houve diferença significante entre os grupos, em relação à freqüência cardíaca (G Controle > G Clon) e pressões do átrio direito e da artéria pulmonar ocluída (G Clon > G Controle). Durante o pinçamento aórtico, houve nos dois grupos, aumento significante das pressões de átrio direito e artéria pulmonar ocluída, dos índices sistólico e do trabalho sistólico do ventrículo esquerdo, e diminuição do índice de resistência vascular pulmonar. No grupo controle houve aumento significante das pressões arterial média e da artéria pulmonar, e dos índices cardíaco e do trabalho sistólico do ventrículo direito. No grupo clonidina, houve diminuição significante da freqüência cardíaca. Após o despinçamento aórtico, houve nos dois grupos: diminuição significante da freqüência cardíaca e pressão arterial média, enquanto os valores das pressões do átrio direito e índice sistólico continuaram elevados. No grupo controle, os valores do índice de trabalho sistólico do ventrículo direito continuaram elevados enquanto os valores do índice cardíaco retornaram a valores próximos aos do controle. No grupo clonidina, os valores das pressões do átrio direito e da artéria pulmonar ocluída, e o índice sistólico, continuaram significantemente elevados. CONCLUSÕES: No cão, nas condições experimentais empregadas, a administração venosa contínua de clonidina atenua as respostas cardiovasculares decorrentes do pinçamento aórtico infra-renal.

DNA damage in patients who underwent minimally invasive surgery under inhalation or intravenous anesthesia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Emergence agitation in pediatric anesthesia: current features

Objective: Postoperative agitation in children is a well-documented clinical phenomenon with incidence ranging from 10% to 67%. There is no definitive explanation for this agitation. Possible causes include rapid awakening in unfamiliar settings, pain (wounds, sore throat, bladder distension, etc.), stress during induction, hypoxemia, airway obstruction, noisy environment, anesthesia duration, child's personality, premedication and type of anesthesia. The purpose of this paper is to discuss the possible causes of postoperative agitation in children, providing a foundation for better methods of identifying and preventing this problem.Sources: MEDLINE and PubMed were searched using the following words: emergence, agitation, incidence, etiology, diagnosis, treatment, children, pediatric, anesthesia.Summary of the findings: This study includes a review of potential agitation trigger factors and a proposal for a standardized diagnostic score system, in addition to measures to improve prevention and treatment.Conclusion: No single factor can identified as the cause of postoperative agitation, which should therefore be considered a syndrome made up of biological, pharmacological, psychological and social components, and which anesthesiologists and pediatric intensive care specialists should be prepared to identify, prevent and intervene appropriately as necessary.

Clonidina como droga adjuvante no tratamento da síndrome de abstinência alcoólica em unidade de terapia intensiva: relato de caso

JUSTIFICATIVA E OBJETIVOS: A sedação de dependentes de álcool e drogas em Unidades de Terapia Intensiva (UTI) é um desafio pela elevada incidência de tolerância às drogas sedativas e da elevada freqüência de síndromes de abstinência. O objetivo deste relato é mostrar um caso de paciente jovem admitido na UTI que desenvolveu síndrome de abstinência alcoólica e tolerância às drogas sedativas, solucionadas somente após o uso de clonidina. RELATO do CASO: Paciente do sexo masculino, 18 anos, dependente de álcool, tabaco, cocaína e maconha, vítima de acidente por arma de fogo, foi admitido na UTI no 1º dia de pós-operatório de enterectomia, após aspiração de conteúdo gástrico durante reintubação traqueal. Evolução clínica: drogas vasoativas até o 4º dia de internação e broncopneumonia bilateral com derrame pleural e necessidade de ventilação artificial até o 15º dia. O esquema de sedação inicial utilizado foi a associação de midazolam e fentanil. A partir do 4º dia, o paciente apresentou vários episódios de agitação psicomotora, mesmo com a associação de lorazepam no 6° dia. No 9° dia, o paciente recebeu as maiores doses dos fármacos, mas permanecia agitado. Optou-se pela associação de dexmedetomidina, que reduziu as doses das outras drogas em 35% e diminuiu a agitação. No 12° dia, o midazolam e a dexmedetomidina foram substituídos pela infusão de propofol, com piora do quadro. No 13° dia, foi associada clonidina ao esquema de sedação, com resolução do quadro de agitação. No 14° dia, o propofol foi suspenso, sendo mantida a infusão de fentanil e reintroduzida a infusão de midazolam, com doses respectivamente 75% e 65% menores em relação ao pico de uso destas drogas. No 15° dia, o paciente foi extubado e teve alta da UTI. CONCLUSÕES: A droga de escolha para o tratamento da síndrome de abstinência alcoólica é o benzodiazepínico. Entretanto, no presente relato, somente o uso adjuvante de clonidina conseguiu proporcionar tratamento adequado ao paciente.