Effects of opium tincture on the enteric and central nervous systems: A randomized controlled trial.

Opioids change gut motility, and opium tincture has been used for treatment of chronic diarrhoea for centuries. However, the effects have never been documented in controlled trials. We aimed to investigate the effects of opium tincture on gastrointestinal transit and motility, frequency of bowel movements, stool consistency, gastrointestinal symptoms and sedation. Twenty healthy subjects were included in this randomized controlled trial. Opium tincture or placebo was each applied for 9 days. Gastrointestinal transit and motility were investigated with the 3D-transit system. Bowel movements and gastrointestinal symptoms were recorded daily. General cognition, reaction time, memory and electroencephalography were used to assess effects on the central nervous system. Opium tincture doubled colonic transit (49 vs. 23 h, p < 0.001), decreased antegrade colonic movements (p < 0.05), reduced daily bowel movements (0.7 vs. 1.2, p < 0.001) and increased stool consistency (Type 3 vs. Type 4, p < 0.001). No changes in general cognition, reaction time or memory were observed, and minor changes of power observed by electroencephalography did not indicate sedation. This study is the first to show that opium tincture has anti-propulsive properties in the healthy gut, while no sedative effects were seen. This indicates that opium tincture is a relevant and safe treatment option in chronic diarrhoea.

Síndrome de Hiper IgD: espectros clínicos, achados genéticos e condutas terapêuticas / Hyper-IgD syndrome: clinical spectrum, genetic findings, and therapeutic approaches

A deficiência de mevalonato quinase (MVK; MIM #142680; ORPHA #343) é uma doença genética, espectral, rara, associadas a mutações ao longo do gene MVK causando distúrbios na síntese do colesterol, que culminam em: inflamação sistêmica com febre, adenopatia, sintomas abdominais e outros achados clínicos. Enquanto no polo leve da doença os achados mais comuns são febres recorrentes com linfadenopatia, no polo mais grave adiciona-se o acometimento do sistema nervoso central (meningites assépticas, vasculites e atraso do desenvolvimento neuropsicomotor) e do sistema hematopoiético (síndrome de ativação macrofágica). Apesar de inúmeras terapêuticas, os bloqueadores da interleucina-1 ainda são os únicos medicamentos capazes de controlar a doença e de impedir a evolução para amiloidose. Os estudos atuais visam tentar novos tratamentos, como o transplante de células-tronco hematopoiéticas, ou mesmo a terapia gênica.

Mevalonate kinase deficiency (MVK; MIM #142680; ORPHA #343) is a rare spectral genetic disorder linked to mutations along the MVK gene leading to impaired cholesterol synthesis, clinically observed as systemic inflammation with fever, adenopathy, abdominal manifestations, and other clinical findings. While on mild forms recurrent fever with lymphadenopathy is commonly observed, severe forms add to that neurological (aseptic meningitis, vasculitis, and neuropsychomotor developmental delay) and hematopoietic involvement (macrophage activation syndrome). Despite of several therapeutic approaches, blocking interleukin-1 is the only effective method to control the disease and prevent the development of systemic amyloidosis. Ongoing studies aim to test new treatments, such as hematopoietic stem cell transplantation and gene therapy.

Thalamic neuron theory: theoretical basis for the role played by the central nervous system (CNS) in the causes and cures of all diseases.

The Thalamic Neuron Theory (TNT) postulates that the central nervous system (CNS) is involved in all disease processes, as the CNS not only processes incoming physical and chemical information from the periphery, it also sends out physiological commands to the periphery in order to maintain homeostasis for the entire body. Inherent in its capacity to learn and adapt (i.e. to habituate) is the CNS' ability to learn to be sick (pathological habituation) by looking in certain deranged central neural circuitries, leading to chronic disease states. These pathologically habituated states can be reversed by dehabituation through manipulation or modulation of the abnormal neural circuits by physical means (physical neuromodulation) like acupuncture, or chemical means (chemoneuromodulation) such as Chinese medicine, homeopathy or other modern medical techniques in a repetitious manner to mimic the habituation process. Chemoneuromodulation can also be achieved by delivery of minute amounts of pharmacological agents to specific sites in the periphery such as the acupuncture loci. It is hypothesized that humoral and neurotrophic factors and cytokines could be highly effective neuromodulating agents. TNT assumes the blue print for embryological development is embodied in the phylogenetically ancient part of the brain. This primordial master plan, organized in the form of a homunculus, possibly encased in a small nucleus, retains control over the subsequently evolved parts of the brain so that the entire CNS functions like a composite homunculus which controls the physiological functions of the entire body. TNT further postulates that the master homunculus takes the shape of a curled up embryo with its large head buried close to its pelvic region, with its large feet and hands crossed over to the contralateral sides. Neuronal clusters along a neuronal chain in the homunculus represent acupuncture points in the periphery. The neuronal chain itself represents a meridian and Chi is nothing more than the phenomenon of neurotransmissions. Certain new theoretical concepts such as the principles of Adynamic Stat and Bilaterality are also presented. Many difficult to explain clinical observations in modern medicine, Chinese herbal medicine, acupuncture and homeopathy can now be adequately explained using TNT. Based on this model, new therapeutic techniques can be launched to combat a whole host of intractable diseases.

[Lipid peroxidation of central nerve system in aged guinea pig and antioxidation effect of the method extract from Pegasus laternarius].

OBJECTIVE: To study the lipid peroxidation products level in aged animals central nerve system and the antioxidation effect of the methol extract from Pegasus laternarius. METHODS: The lipid peroxidation product MDA was tested by spectrophotometer. RESULTS: Compared with the 10 month-old guinea pig, the MDA in 32 month-old guinea pig central nerve system obviously elevated, there were some difference in different fields of tested guinea pig brain, the level of MDA in hypothalamus increased biggest (up to 161.7%), cerebral cortex 93.7%, cerebella 84.9%, brain stem 81.2%, spinal cord 90.7%, rest of the cerebrum 58.9%. The method extract from Pegasus laternarius 10, 20, 40 mg/kg and ginseng saponin 20 mg/kg could reduce the level of MDA in tested brain field of aged animals. The method extract from Pegasus laternarius had stronger activity in brain stem, spinal cord and hypothalamus. CONCLUSION: The lipid peroxidation in aged animal may be increased, the method extract from Pegasus laternarius and ginseng saponin have a protective effect on neuron in central nerve system of aged animals from free radical hurt.

Central nervous system effects of intrathecal muscle relaxants in rats.

When given for a sufficient time and dose intravenously, neuromuscular blocking drugs eventually can enter the cerebrospinal fluid (CSF). To study the potential pharmacologic consequences of neuromuscular blocking drugs in the CSF, a model was developed in the rat by using an intrathecal infusion of these drugs. A cannula was stereotaxically implanted in a lateral cerebral ventricle of anesthetized male Sprague-Dawley rats (250-300 g). Several days later, the effects of an intraventricular infusion (5 microL/min) of atracurium (0.804 mumol/mL), pancuronium (0.172 mumol/mL), and vecuronium (21.978 mumol/mL) were studied in unanesthetized rats. These rats (n = 6 in each group) exhibited dose-dependent hyperexcitability, during drug infusion, with seizures occurring at threshold doses of (mean), 0.12, 0.26, and 0.065 +/- 0.010 and 3.32 mumol/kg of atracurium, pancuronium, and vecuronium, respectively. The neuromuscular ED50 (intravenous dose required to produce a 50% depression of twitch tension) in rats determined by other investigators are 0.408, 0.115, and 0.352 mumol/kg for atracurium, pancuronium, and vecuronium, respectively. Therefore, seizure threshold doses were not related to the potencies of these drugs as neuromuscular blocking drugs. Based on these data, central nervous system effects were studied over the subseizure dose range approximating 1/100, 1/10, and 1/5 of the cumulative dose causing seizures for each drug (n = 5 for each dose). At 1/100 of seizure dose, decreased locomotor activity and piloerection occurred. At 1/10 to 1/5 of seizure dose, agitation, shivering, splayed limbs, and whole body shaking resulted.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrous oxide antagonizes CNS stimulation by laudanosine in mice.

We have investigated whether nitrous oxide antagonizes or augments the CNS stimulant action of laudanosine in mice by comparing the mean convulsive doses (CD50 (SE] of a control group and those following pretreatment with 65% nitrous oxide in oxygen for 20 and 180 min. Nitrous oxide significantly increased CD50 from 46.8 (1.4) mg kg-1 of control to 57.3 (1.3) mg kg-1 at 20 min and 53.5 (1.7) mg kg-1 at 180 min. The attenuation of the effect of nitrous oxide at 180 min, suggestive of possible partial drug tolerance, was not statistically significant. These findings indicate that nitrous oxide antagonizes the CNS stimulating action of laudanosine.

[Evaluation of the pharmacological properties of a new steroid curarelike agent, RGH 1106]. / Otsenka nekotorykh farmakologicheskikh svoistv novogo steroidnogo kurarepodobnogo sredstva RGH 1106.

Tests on cats showed the compound RGH 1106 to possess an antidepolarizing mechanism of action. The sequence of myorelaxation, arising under the effect of this agent, is characterized by relaxation in the first place of the musculus masseter, muscles of limbs, then of abdominal muscles and those of the diaphragm and, finally, of the intercostal muscles. RGH 1106 doses not possess cardiotropic m-cholinolytic action, does not exert a ganglion blocking effect, nor affects the central nervous system. It neither changes the blood supply of the myocardium and the uptake of oxygen by the latter, nor inhibits the acetylcholinesterase.

Neonatal abstinence syndrome: assessment and management.

A scoring system for the neonatal abstinence syndrome has been devised and implemented as both a clinical and investigative tool. The score monitors the passively addicted infant in a more comprehensive and objective fashion, and facilitates a more precise evaluation of the clinical status of the infant undergoing withdrawal. In addition, the scoring system has been applied in research designed to test the comparative usefulness of various pharmacologic agents currently recommended for the neonatal abstinence syndrome, and has been found useful in following the progression and diminution of withdrawal symptomatology before, during, and after therapy. Furthermore, the scoring system provides a basis ofr developing uniform criteria for the assessment and treatment of the neonate born to the addicted mother.

The assessment of behavioral change in infants undergoing narcotic withdrawal: comparative data from clinical and objective methods.

Studies comparing objective measures of sucking with data from finegrained clinical assessments of the neonate have shown significant correlations between painstaking and time-comsuming clinical methods which may only be reliably applied by highly trained clinician-investigators, and the data generated by a simple technique which can be rapidly and precisely administered in the nursery by nurses or technicians. Within a few minutes the sucking instrument can generate data that explain 50% or more of the variance in certain relevant factors of the Brazelton neonatal neurobehavioral assessment scale, which in our hands requires the participation of two trained clinician-investigators for a period of almost one hour for each test and recording session. There are certain limitations to the information directly available from the sucking measures. Clinical observations must be made in order to correctly interpret some of the findings such as the biphasic relationship between irritability and sucking. For example, an infant may not suck at all because it is obtunded, or it may not suck because it is overexcited. In the case of irritability, sucking performance provides a measure of the magnitude, but not of the polarity of the CNS arousal sucking correlates directly and gives a good estimate of both polarity as well as amount of these behaviors. Objective measures of sucking behavior are a convenient and reliable means for measuring drug effects in the nursery and may be useful in regulating therapy of the newborn.

Levobupivacaína: ¿Una nueva opción? / Levobupivacaine: A new option?

La investigación de nuevos anestésicos locales con un aumento de la liposolubilidad de sus moléculas ha permitido hallar drogas con mayor potencia y duración del efecto. Sin embargo, los mismos cambios moleculares que incrementan la duración de acción y la potencia también pueden aumentar la toxicidad local y sistémica. En el caso de una excesiva dosis utilizada, ya sea por una rápida absorción o por una inyección intravascular inadvertida, durante el procedimiento para el bloqueo se pueden producir efectos sistémicos de importancia. El primer sistema afectado es el nervioso central, donde produce una excitación, llegando luego a deprimir el sistema cardiovascular. Los estudios comparativos para numerosas indicaciones no han podido demostrar fehacientemente diferencias en cuanto a la toxicidad de la levobupivacaína, la ropivacaína y la bupivacaína.

Hipóteses fisiopatológicas e considerações terapêuticas da acatisia induzida por antipsicóticos / Pathophysiological hypothesis and therapeutic considerations of neurolepticðinduced akathisia

A fisiopatologia da acatisia induzida por antipsicóticos não está totalmente compreendida. Muitas hipóteses propostas têm demonstrado o possível envolvimento de diversas vias neuronais do sistema nervoso central, incluindo os sistemas noradrenérgico, dopaminérgico, serotoninérgico, colinérgico e gabaérgico. Os autores apresentam hipóteses fisiopatológicas e considerações terapêuticas da acatisia induzida por antipsicóticos