Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats

The heme oxygenase-carbon monoxide pathway has been shown to play an important role in many physiological processes and is capable of altering nociception modulation in the nervous system by stimulating soluble guanylate cyclase (sGC). In the central nervous system, the locus coeruleus (LC) is known to be a region that expresses the heme oxygenase enzyme (HO), which catalyzes the metabolism of heme to carbon monoxide (CO). Additionally, several lines of evidence have suggested that the LC can be involved in the modulation of emotional states such as fear and anxiety. The purpose of this investigation was to evaluate the activation of the heme oxygenase-carbon monoxide pathway in the LC in the modulation of anxiety by using the elevated plus maze test (EPM) and light-dark box test (LDB) in rats. Experiments were performed on adult male Wistar rats weighing 250-300 g (n=182). The results showed that the intra-LC microinjection of heme-lysinate (600 nmol), a substrate for the enzyme HO, increased the number of entries into the open arms and the percentage of time spent in open arms in the elevated plus maze test, indicating a decrease in anxiety. Additionally, in the LDB test, intra-LC administration of heme-lysinate promoted an increase on time spent in the light compartment of the box. The intracerebroventricular microinjection of guanylate cyclase, an sGC inhibitor followed by the intra-LC microinjection of the heme-lysinate blocked the anxiolytic-like reaction on the EPM test and LDB test. It can therefore be concluded that CO in the LC produced by the HO pathway and acting via cGMP plays an anxiolytic-like role in the LC of rats.

Tuberculosis in renal transplant patients: The experience of a single center in Medellín-Colombia, 2005-2013 / Tuberculose em pacientes transplantados renais: experiência de um único centro em Medellín-Colômbia, 2005-2013

Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .

Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .

protective effect of vitamin E on locus coeruleus in early model of parkinsons disease in rat: immunoreactivity evidence

Free radical formation and oxidative stress might play an important role in the pathogenesis of Parkinson's disease [PD]. In vitro data indicate that neuromelanin [NM] pigment is formed the excess cytosolic catecholamine that is not accumulated into synaptic vesicles via the vesicular monoamine transporter 2 [VMAT2]. We designed this study to investigate the neuroprotective effects of vitamin E in the early model of PD. Male rats [n = 40] with unbiased rotational behavior were randomly divided into five groups: sham operated group [SH, n = 8], vehicle-treated SH group [SH + V, n = 8], vitamin E-treated SH group [SH + E, n = 8], vehicle-treated lesion group [L + V, n = 8] and vitamin E-treated lesion group [L + E, n = 8]. Unilateral intrastriatal 6-hydroxydopamine [12.5 micro l] lesioned rats were treated intramuscularly with alpha-tocopherol acid succinate [24 I.U/kg, intramuscular [i.m.]] 1 h before surgery and three times per week for 2 month post-surgery. To evaluate the vitamin E pretreatment efficacy, tyrosine hydroxylase [TH] immunoreactivity and immunostaining intensity [ISI] for monoamine transporter 2 were used. TH immunohistochemical analyses showed a reduction of 20% in locus coeruleus [LC] cell number of vitamin E pretreated lesioned group but the cell number dropped to 60% in the lesioned group. The ISI of the cells was measured for VMAT2 in LC. Lesioned groups: 1] had the lowest VMAT2 ISI of all neurons; 2] There was an inverse relationship between VMAT2 ISI and NM pigment in the locus and 3] Neurons with the highest VMAT2 ISI also had high TH ISI. The data support the hypothesis that repeated i.m. administration of vitamin E exerts a protective effect on the LC neurons in the early model of PD

[Effects of Matricaria chamomilla extract injection into paragigantocellularis nucleus on morphine withdrawal signs in rats]

Reports suggest that co-administration of Matricaria Chamomilla [MC] extract with morphine greatly attenuates the dependence on morphine and its injection prior to naloxan inhibits the withdrawal syndrome. Locus Ceruleus [LC] and paragigantocellularis [PGi] nuclei play a key role in appearance of withdrawal syndrome. Thus, this study was conducted to determine the effects of MC extract injection into pGi nucleus on morphine withdrawal in rats. 30 rats [Weighing 250-300gr] were divided into two groups of control [receiving saline] and morphine-treated. Following surgical implantation of cannula, morphine-treated group received morphine twice daily for 7 days. This group was classified into 4 sub-groups.The first sub-group received only morphine while the three remaining sub-groups were administed with Matricaria Chamomilla on day 7, five minutes prior to 1 microliter naloxan injection, with 10, 25, and 50 micro gr/lit, respectively. In all groups 5 mg/kg naloxan was injected 3 hours after the final injection of morphine and withdrawal behavior [jumping and climbing] was investigated for 30 minutes. The results showed that injection of all three high doses of MC extract particulary 25 microgr/microlit into PGi nuclens could significantly decline the symptoms of withdrawal syndrome. It seems that injection of MC extract into PGi nucleus could be beneficial to the treatment of morphine withdrawal syndrome in rats

Electroencephalographic study of the effect of neurotoxin DSP-4 in iron model of chronic focal epilepsy.

The effect of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on electroencephalographic activity (EEG) was studied in the model of chronic focal epilepsy induced by intracortical injection of FeCl3 in the rat. EEG activity was recorded from the epileptogenic focus (ipsilateral and contralateral) in chronic experiments before and after DSP-4 treatment. In some experiments EEG activity was also simultaneously recorded from the cortical epileptogenic focus and locus coeruleus before and after DSP-4 treatment to study the effect of iron-induced seizure activity and of DSP-4 on the locus coeruleus electrical activity. The results showed that DSP-4 aggravated the iron-induced epileptiform activity as well as the locus-coeruleus electrical activity. The data also showed that, induction of epilepsy by FeCl3 is accompanied by enhancement of the locus coeruleus electrical activity. Our study demonstrates that DSP-4 intensifies and modifies the epileptic activity in the iron-induced chronic epilepsy model and that the effects of toxin persist for a longer duration.

Distúrbio de pânico e comorbidade clínica / Panic disorder and clinical comorbidity

Os autores abordam o distúrbio do pânico considerando nao só as manifestaçoes psiquiátricas mas também as possibilidades biológicas bem como as várias patologias que podem cursar com sintomatologia semelhante às crises de pânico.