RESUMO
RATIONALE: Serotonin (5-HT) is a monoamine neuromodulator that plays a key role in the organization of the central nervous system. 5-HT alterations may be associated to the emergence of social deficits and psychiatric disorders, including anxiety, depression, and substance abuse disorders. Notably, disruption of the 5-HT system during sensitive periods of development seems to exert long-term consequences, including altered anxiety responses and problematic use of alcohol. OBJECTIVE: We analyzed, in mice, the effects of transient 5-HT depletion at gestation (a developmental stage when medial prefrontal cortex (mPFC) 5-HT levels depend exclusively on placental 5-HT availability) on 5-HT central synthesis and reuptake at weaning. We also explored if 5-HT disruption at the embryonic stage influences behavioral outcomes that may serve as a proxy for autistic- or anxiety-like phenotypes. METHODS: C57/BL6 male and female mice, born from dams treated with a 5-HT synthesis inhibitor (PCPA; 4-Chloro-DL-phenylalanine methyl ester hydrochloride) at gestational days (G)13.5-16.5, were subjected to a behavioral battery that assesses social preference and novelty, compulsive behavior, stereotypies, and ethanol's anti-anxiety effects, at postnatal days (P) 21-28. Afterwards, expression of the genes that encode for 5-HT synthesis (Tph2) and SERT (5-HT transporter) were analyzed in mPFC via real-time RT-PCR. Dopamine 2 receptor (D2R) expression was also analyzed via RT-PCR to further explore possible effects of PCPA on dopaminergic transmission. RESULTS: Transient 5-HT disruption at G13.5-16.5 reduced Tph2 expression of both male and female mice in mPFC at P23. Notably, female mice also exhibited higher SERT expression and reduced D2R expression in mPFC. Mice derived from 5-HT depleted dams displayed heightened compulsive behavior at P21, when compared to control mice. Alcohol anti-anxiety effects at early adolescence (P28) were exhibited by mice derived from 5-HT depleted dams, but not by control counterparts. No social deficits or stereotyped behaviors were observed. CONCLUSION: Transient 5-HT inhibition at gestation resulted in altered expression of genes involved in 5-HT synthesis and reuptake in mPFC at weaning, a period in which the 5-HT system is still developing. These alterations may exert lingering effects, which translate to significant compulsivity and heightened sensitivity to the anxiolytic effects of alcohol at early adolescence.
Assuntos
Ansiolíticos , Serotonina , Animais , Ansiolíticos/farmacologia , Comportamento Animal , Dopamina/metabolismo , Etanol/farmacologia , Feminino , Fenclonina/farmacologia , Humanos , Masculino , Camundongos , Placenta/metabolismo , Gravidez , Piridinolcarbamato , Serotonina/metabolismo , DesmameRESUMO
BACKGROUND: Chemotherapy-associated liver injury (CALI) is a matter of concern for hepatobiliary surgeons as it can entail postoperative liver failure after an extensive hepatectomy. Recent studies have taken special interest in liver function parameters which can correlate with CALI to decrease this adverse event. Therefore, the current study investigates the usefulness of splenic volume as a biomarker of CALI through a portal hypertension mechanism, in patients with colorectal liver metastases (CRLM). STUDY DESIGN: We carried out a study in patients with CRLM operated on between 2009 and 2014 in our center. All samples of healthy liver were graded for non-alcoholic fatty liver disease (NAFLD) and sinusoidal obstructive syndrome. Computarized tomography scans for spleen volumetry were analyzed for each patient at CRLM diagnosis, after neoadjuvant chemotherapy, 1 and 6 months after resection. RESULTS: A group of 65 consecutive patients with CRLM of large bowel adenocarcinoma submitted to liver resection were included. Patients receiving neoadjuvant chemotherapy had a greater spleen volume increase than those who did not receive treatment (p = 0.053), finding a statistically significant spleen growth in patients with NAFLD (p = 0.036). There was no correlation between spleen enlargement and postoperative complications or average stay. However, survival was decreased in patients with spleen growth and CALI. CONCLUSIONS: Patients who receive neoadjuvant chemotherapy for liver metastasis surgery have a greater splenic volume increase, which correlates with NAFLD and a lower survival.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Neoplasias Colorretais/patologia , Hepatectomia , Hepatopatia Veno-Oclusiva/patologia , Neoplasias Hepáticas/terapia , Hepatopatia Gordurosa não Alcoólica/patologia , Baço/diagnóstico por imagem , Adenocarcinoma/secundário , Antineoplásicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Hepatopatia Veno-Oclusiva/induzido quimicamente , Humanos , Neoplasias Hepáticas/secundário , Metastasectomia , Terapia Neoadjuvante , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Tamanho do Órgão , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Complicações Pós-Operatórias , Baço/patologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
In a nonblinded, therapeutic trial conducted in Colombia, 1.25-1.5 grams of mefloquine base given as a single oral dose or as 250 mg a day for 5-6 consecutive days was not efficacious in the treatment of New World cutaneous leishmaniasis. The drug had cured only 30.8 % of patients with leishmaniasis skin lesions by the 10th week after start of therapy as compared with a 27.9% complete cicatrization rate in historical controls treated with placebo tablets and an 86.3% cicatrization rate in historical controls who received meglumine antimoniate, 20 mg/ kg/day intramuscularly for 20 days, with no upper limit to daily dose. It is concluded that a single course treatment with mefloquine is not indicated as monotherapy in the treatment of Colombian cutaneous leishmaniasis primarily due to L. panamensis.
Assuntos
Antimaláricos/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Mefloquina/uso terapêutico , Adolescente , Adulto , Feminino , Humanos , Masculino , Mefloquina/efeitos adversos , Pessoa de Meia-IdadeRESUMO
An eco-epidemiological study was carried out in the region of the Alpujarras (southern Spain, Granada province). Nine villages were chosen at random in 5 bioclimatic zones. A study of leishmaniasis in the canine and human populations, was carried out concentrating especially upon schoolchildren. A total of 615 dogs were screened, which represents almost 100% of the canine census. Of the screened dogs, 33 showed an antibody titer > or = 1/160 when tested by IFA (seroprevalence of 5.3%). Age, sex, activity, and clinical symptoms of each dog were taken into account. Among the human population, infection from Leishmania was studied using the Leishmanin skin test (LST). Of 1286 people who were tested, 568 (44.16%) were positive. Most of the subjects were schoolchildren (878; practically 100% of the pupils), of whom 288 (32.8%) tested positive. A close relation was seen to exist between the percentage of positive LST's and age. Finally, a close relationship was also observed between canine seroprevalence and percentage of schoolchildren who tested positive in the LST, in the 5 bioclimatic zones under consideration.