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The aim of this research was to find out the effects of ip morphine pretreatment in the extracellular content of the arginine, glutamate, aspartate and GABA levels in the anterior cingulate cortex in rats, during the formalin test (phase I). A combination of micro dialysis and Capillary Electrophoresis Zone and laser-induced fluorescence detection (CZE-LIFD) technique was used to measure the extracellular levels of amino acids in microdialized zones. The microdialysis probes were unilaterally implanted in the left anterior cingulate cortex of freely moving rats. The samples were collected every 30 seconds and derivatized with fluorescein isothiocianate. The arginine, glutamate, aspartate and GABA levels were measured in the CZE-LIFD device. Arginine (p<0.001) and glutamate levels (p<0.012) were significantly increased in the first few minutes following the formalin test (phase 1). Pretreatment with morphine suppressed the glutamate increase. A transient GABA level increase (p<0.001) was also detected. These experiments suggest that rapid changes in neurotransmitters levels were detected in the first few minutes of acute pain as revealed by the glutamate and arginine level increases in the anterior cingulate cortex. These changes could be related to the emotion of pain processing (fear and aversion). Morphine pretreatment produced an increase in GABA levels and a decrease in glutamate levels in the first few minutes. These findings may be related to euphoria and/or analgesia.

The antipsychotic drugs (APDs) are fundamental tools in current psychiatric practice. A new generation of agents, the atypical APDs, represents an important progress in the treatment of psychotic disorders. Unfortunately, some of them induce excessive body weight gain (BWG), obesity, hyperglycemia and dyslipidemia in the following order: clozapine approximately equal to olanzapine > quetiapine > risperidone > ziprasidone = aripiprazole. Appetite stimulation is probably the main mechanism of BWG and this is strongly correlated with the APD affinity for H1 (histaminergic) and alpha1 (adrenergic) receptors. A composed ratio of the APD affinity for diverse neurotransmitters involved in food intake (FI) regulation correlates with BWG as well. Endocrine/metabolic mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis, changes in insulin sensitivity (by conventional and atypical agents), hyperprolactinemia and gonadal dysfunction (by conventional APDs and risperidone) may also be involved. Importantly, patients with schizophrenia may have a genetically-based predisposition to appetite dysregulation, insulin resistance and endocrine imbalance involving gonadal steroids. Excessive BWG must be prevented or attenuated by proper drug selection, combining or switching agents, nutritional assistance and physical exercise. Amantadine. metformin and reboxetine proved to significantly lessen APD-induced BWG. Notwithstanding this, novel strategies are necessary to treat this side effect in a clinical population particularly prone to poor compliance and under a high risk of negative drug interaction.

Scorpion human envenoming is a public health hazard in the southwest of Venezuela. Tityus zulianus is one of the scorpion species whose venom causes lung edema and cardiac failure in children. These occasionally deadly manifestations have been attributed to a massive sympathetic discharge. The intraperitoneal administration of T. zulianus venom (20 micrograms/g mouse) to anesthetized mice during subcutaneous microdialysis caused increased secretions, dyspnea, seizures and death between 30 min to 2 h. Seven amino acids were analyzed by capillary electrophoresis with laser induced fluorescence detection (CE-LIFD) in the collected samples before and after the venom administration. We found an increase of arginine (39%), phenylalanine (40%) and glutamate (94%), with no changes in valine, serine and aspartate, changes were significant when the injection of venom and vehicle were compared and before vs after venom injection. Further investigation is needed to know if the observed changes could be related to the molecular mechanisms of the venom or some of its components and therefore with the envenoming symptoms. To our knowledge, this is the first report with subcutaneous microdialysis and CE-LIFD coupling in scorpion envenomation studies in vivo, in mice.

Microdialysis is a simple technique that allows monitoring endogenous or exogenous substances in any extracellular compartment. It has many useful experimental and clinical applications. The sampling of the extracellular fluid of the subcutaneous compartment is especially useful for metabolic evaluation in critically ill patients, pharmacokinetic studies and blood glucose monitoring. We built a subcutaneous microdialysis probe, with a cellulose hollow fiber (13,000 molecular weight cut off, 200 microns outside diameter) glued to stainless steel tubing (26 ga. outside diameter). It was implanted in the subcutaneous tissue of a critically ill child or anesthetized mice to obtain amino acids patterns by means of capillary electrophoresis with laser induced fluorescence detection (CE-LIFD). The probe was also implanted in ambulatory volunteers to monitor glucose. The results confirmed that subcutaneous microdialysis is a very simple, inexpensive and not aggressive method with advantages over repeated venipuncture sampling and endovenous microdialysis sampling. The present report shows that subcutaneous microdialysis with the proper analytical technique can be used to monitor the chemical composition of the interstitial compartment in very different preclinical or clinical conditions.

Aims: The objective of this study is to survey present and future antidepressant drug therapy based on the progress made in the field of biotechnology., Development: The simplistic and mistaken view that one single system of neurotransmission is altered in depression and that there is, therefore, just one single treatment has changed. Molecular biology and Genetics have enabled us to determine other possible chemical alterations in the brain, beyond the sole participation of the monoaminergic modulation systems, which is the classical hypothesis. In this paper we describe the evidence for the relations between depression and the therapeutic effect the classical antidepressants have on: 1. The peptidergic system of the corticotropin-releasing hormone, cortisol and the functional state of its receptors; 2. Intracellular signalling systems such as cAMP on transcription factors like CREB and neurotrophins; 3. The immune system and cytosines; 4. Glutamate transmission; and 5. The neuropeptidergic system of substance P, neuroactive steroids and the neuroglia. This has allowed other biochemical hypotheses about depression and the possibility of new treatments to be put forward., Conclusions: We are still not certain about the exact cause or the processes that determine mental illnesses such as depression or how improvements are achieved with the antidepressants we currently have available. Nevertheless, biotechnology is expected to be a great help in advancing towards a better understanding of the interrelations between the nervous, immune and endocrine systems, with their intracellular cascades and final outcomes in genetic expression and protein function, in depression. This will enable more efficient, more selective and faster-acting drugs to be developed and, in the future and with the help of psychogenomics, even make it possible to produce tailor-made medication for each patient.

Geranium has been traditionally used as a local hemostatic medicine in some Andean regions, but this effect has not been tested in controlled experiments. In the present report, the leaves of a geraniaceae (Pelargonium zonale) were tested on a bleeding rat model. The bleeding time was 50% shorter in the geranium leaf juice treatment group (18.10 +/- 2.03 min) and 80% shorter in the geranium crushed-leaf group (7.10 +/- 0.88 min) than in the control (nontreatment) group (37.6 +/- 3.04 min), p < 0.0001. Bleeding time with guava (Psidium guajava) crushed leaves (39.90 +/- 1.54 min) was not different from the control group. A proved hemostatic agent, gelatin sponge, had a similar effect as geranium juice (16.7 +/- 3.32 min) in the same animal model. A buffer solution at pH 3 (the same pH as the geranium leaf extract) did not have any hemostatic effect, and the bleeding time (39.3 +/- 2.71 min) was not different from the control group. The dilution 1:4 geranium leaf juice at pH 3(25.6 +/- 3.08 min) or pH 5 (28.8 +/- 3.98 min) still had a statistically significant hemostatic effect. The results confirm the hemostatic effect of P. zonale leaves and show that it is similar (geranium leaf juice) or better (crushed geranium leaves) than the hemostatic effect of a commercial hemostatic sponge. It seems that the hemostasis caused by P. zonale extract leaves is not due to its low pH. The potential benefits as a new, inexpensive, safe, and easily available natural topical hemostatic agent are discussed.

Capillary electrophoresis (CE) is a high-efficiency analytical technique that has had a great impact as a tool in biomedical research, clinical and forensic practice in the last ten years. Only in one of the applications, the DNA analysis, it has had an explosive exponential growth in the last few years. This impact is expressed in an enormous amount of CE articles and many reviews. The CE advantages with respect to other analytical techniques: the required very small sample volume, rapid analysis, great resolution power and low costs, have made this technique ideal for the analysis of a numerous endogenous and exogenous substances present in biological fluids. The different modes of CE have been coupled to different detection techniques such as UV-absorbance, electrochemical, mass spectrometry and laser-induced fluorescence detection (LIFD) to detect different nature and molecular size separated analytes. This review focuses mostly on the applications of CE-LIFD, to measure drugs and endogenous neuroactive substances such as amino acids and monoamines, especially in microdialysis samples from experimental animals and humans. CE-LIFD trends are discussed: automated faster analysis with capillary array systems, resolution power improvement, higher detection sensitivity, and CE systems miniaturization for extremely small sample volume, in order to make CE easier and affordable to the lab bench or the clinical bed., (Copyright 2001 John Wiley & Sons, Ltd.)

Plasma serotonin (5-HT) active pool was monitored in male volunteers by intravenous microdialysis coupled to HPLC-EC with 98.6% efficient probes. 5-HT was monitored from 60 min before to 360 min after an oral dose of fluoxetine, a 5-HT uptake inhibitor, or vehicle. The basal values were within nanomolar range (0.55 to 4.6 ng/ml). After administration of fluoxetine, there was a significant increment of 5-HT with respect to controls. These results showed that intravenous microdialysis is an alternative efficient technique to monitor endogenous unbound 5-HT changes in plasma without extracting blood or sample pretreatment procedures before the chemical analysis.

1. Obesity is an undesirable side effect of neuroleptics which affects 50% approximately of patients under a program of chronic administration. 2. An animal model of neuroleptic-induced obesity and hyperphagia has been developed in female rats treated chronically with sulpiride (20 mg/Kg/ip. for 21 days). However, it is unknown whether or not the hyperphagia is essential for the development of this type of obesity. 3. Sulpiride or vehicle was administered in two experimental conditions: in the first one, food was available in an amount which was three times the previous individual daily food intake; in the second one, the daily food provision was maintained at the individual daily average before starting the treatments. This way hyperphagia was prevented in half of the groups. Besides the body weight gain measurement in all the groups, the serum levels of estradiol, prolactin, glucose and lipids were assessed in the groups with unrestricted food intake. 4. Food restriction prevented the sulpiride-induced weight gain, even though the rats displayed a permanent diestrus which suggests an hyperprolactinemia-induced impairment in the balance of the reproductive hormones that may promote weight gain. However, the basal levels of estradiol were not affected by sulpiride. 5. The high density cholesterol was significantly increased by sulpiride, and the serum glucose levels were significantly decreased, however these changes were only detected during the first week of treatment. 6. The decrease in the serum glucose levels may be an early consequence of hyperinsulinemia. 7. Neuroleptic-induced obesity in rats appears to mimic energy intake, endocrine status and carbohydrate metabolism in humans under chronic neuroleptic administration. However, these rodents did not display the typical changes in blood lipids observed in human obesity.

Prefrontal cortex microdialysis was done in rats that had received intraperitoneal amphetamine (AMPH). Samples were derivatized with 10(-4) M fluorescein isothiocyanate and incubated for 18 h. AMPH was separated by capillary electrophoresis (CE) and detected by laser-induced fluorescence detection (LIFD) from 30 to 150 min after injection. The limit of mass detection was 3 amol, which is three orders of magnitude lower than that in gas chromatography-mass spectrometry, and the limit of concentration detection was 3 x 10(-9) M. The results showed that CE-LIFD is a good method for detecting AMPH in brain dialysates of rats.

Rationale and Objectives: We examined patterns of use of sonography in the workup of appendicitis at two hospitals: a 715-bed university-affiliated teaching hospital and a 240-bed nonteaching hospital. In light of increasing concern over the use of health care dollars, we wanted to determine whether the use of sonography in the workup of appendicitis would be more frequent at a teaching than at a nonteaching hospital., Methods: We examined all cases of appendicitis seen in the emergency room of the teaching hospital in 1993 and all cases of appendicitis seen in the emergency room of the nonteaching hospital in 1992-1993. Exclusionary criteria included pregnancy, altered mental status, or multiple discharge diagnoses. The diagnosis of appendicitis was verified by pathology reports., Results: At the teaching hospital, the use of sonography was 38.5% (65 of 169); at the nonteaching hospital, sonography usage was 39.4% (61 of 155)., Conclusion: There appears to be no significant difference between teaching and nonteaching hospitals in the frequency of use of sonography in diagnosing patients with appendicitis.

Male rats were castrated before puberty. When they were adult, the activity of their mesolimbic dopamine system was tested by ventral striatum microdialysis. Amphetamine injections increased dopamine more in castrated rats than in normal rats. This exaggerated response was attenuated by testosterone replacement therapy. The mechanism by which androgens modulate the activity of the mesolimbic dopamine system is discussed.