Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases.

(1) Background: Gastrointestinal pain and fatigue are the most reported concerns of patients with inflammatory bowel disease (IBD). Commonly prescribed drugs focus on decreasing excessive inflammation. However, up to 20% of IBD patients in an "inactive" state experience abdominal pain. The medicinal herb Ojeok-san (OJS) has shown promise in the amelioration of visceral pain. However, no research on OJS has been conducted in preclinical models of IBD. The mechanism by which OJS promotes analgesia is still elusive, and it is unclear if OJS possesses addictive properties. (2) Aims: In this study, we examined the potential of OJS to promote analgesic effects and rewarding behavior. Additionally, we investigated if tumor necrosis factor alpha (TNFα) from macrophages is a primary culprit of IBD-induced nociception. (3) Methods: Multiple animal models of IBD were used to determine if OJS can reduce visceral nociception. TNFα-macrophage deficient mice were used to investigate the mechanism of action by which OJS reduces nociceptive behavior. Mechanical sensitivity and operant conditioning tests were used to determine the analgesic and rewarding effects of OJS. Body weight, colon length/weight, blood in stool, colonic inflammation, and complete blood count were assessed to determine disease progression. (4) Results: OJS reduced the evoked mechanical nociception in the dextran sulphate sodium model of colitis and IL-10 knockout (KO) mice and delayed aversion to colorectal distension in C57BL/6 mice. No rewarding behavior was observed in OJS-treated IL-10 KO and mdr1a KO mice. The analgesic effects of OJS are independent of macrophage TNFα levels and IBD progression. (5) Conclusions: OJS ameliorated elicited mechanical and visceral nociception without producing rewarding effects. The analgesic effects of OJS are not mediated by macrophage TNFα.

Site-Specific knockdown of microglia in the locus coeruleus regulates hypervigilant responses to social stress in female rats.

BACKGROUND: Women are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking. METHODS: Microglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3 µg/side, n = 5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25 µg/side, n = 13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance. RESULTS: Intra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1ß (IL-1ß). Further, the efficacy and selectivity of microinjected m-CLD was fully characterized. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1ß. Intra-central amygdala m-CLD had no effect on WS-evoked behavior. CONCLUSIONS: These studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses.

Mutations of tyrosine 467 in the human norepinephrine transporter attenuate HIV-1 Tat-induced inhibition of dopamine transport while retaining physiological function.

Dysregulation of dopaminergic transmission induced by the HIV-1 transactivator of transcription (Tat) has been implicated as a central factor in the development of HIV-1 associated neurocognitive disorders (HAND). We have demonstrated that the tyrosine470 residue of the human dopamine transporter (hDAT) plays a critical role in Tat-hDAT interaction. Based on the computational modeling predictions, the present study sought to examine the mutational effects of the tyrosine467 residue of the human norepinephrine transporter (hNET), a corresponding residue of the hDAT tyrosine470, on Tat-induced inhibition of reuptake of dopamine through the hNET. Mutations of the hNET tyrosine467 to a histidine (Y467H) or a phenylalanine (Y467F) displayed similar kinetic properties of reuptake of [3H]dopamine and [3H]norepinephrine in PC12 cells expressing wild-type hNET and its mutants. Compared to wild-type hNET, neither of Y467H or Y467F altered Bmax and Kd values of [3H]WIN35,428 binding, whereas Y467H but not Y467F decreased the Bmax of [3H]nisoxetine binding without changes in Kd. Y467H also increased the affinity of nisoxetine for inhibiting [3H]dopamine uptake relative to wild-type hNET. Recombinant Tat1-86 (140 nM) induced a significant reduction of [3H]dopamine uptake in wild-type hNET, which was attenuated in both Y467H and Y467F. Compared to wild-type hNET, neither Y467H or Y467F altered [3H]dopamine efflux in CHO cells expressing WT hNET and mutants, whereas Y467F but not Y467H decreased [3H]MPP+ efflux. These results demonstrate tyrosine467 as a functional recognition residue in the hNET for Tat-induced inhibition of dopamine transport and provide a novel insight into the molecular basis for developing selective compounds that target Tat-NET interactions in the context of HAND.

Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer.

Cancer patients can develop visceral, somatic, and neuropathic pain, largely due to the malignancy itself and its treatments. Often cancer patients and survivors turn to the use of complementary and alternative medicine (CAM) to alleviate pain and fatigue. Thus, it is necessary to investigate how CAM therapies work as novel analgesics to treat cancer pain. Ojeok-san (OJS) is an herbal formula consisting of seventeen herbs. This herbal formula has been shown to possess anti-inflammatory, immunoregulatory, and analgesic properties. In this study, we examined the potential beneficial effects and mechanism of action of OJS in a preclinical model of colitis-associated colorectal cancer. Male and female C57BL/6J mice were exposed to the carcinogen, azoxymethane (AOM, 10 mg/kg) and a chemical inflammatory driver, dextran sulfate sodium (DSS1-2%), to promote tumorigenesis in the colorectum. OJS was given orally (500, 1000, and 2000 mg/kg) to determine its influence on disease activity, tumor burden, nociception, sedation, Erk signaling, and behavioral and metabolic outcomes. In addition, in vitro studies were performed to assess CT-26 cell viability, dorsal root ganglia (DRG) activation, and bone-marrow-derived macrophage (BMDM) inflammatory response to lipopolysaccharide stimulation after OJS treatment. We found that administration of 2000 mg/kg of OJS was able to mitigate mechanical somatic and visceral nociception via Erk signaling without affecting symptom score and polyp number. Moreover, we discovered that OJS has sedative properties and elicits prolonged total sleeping time in AOM/DSS mice. Our in vitro experiments showed that OJS has the capacity to reduce TNFα gene expression in LPS-stimulated BMDM, but no changes were observed in DRG spike number and CT-26 cell proliferation. Taken together, these data suggest that OJS ameliorates nociception in mice and warrants further examination as a potential CAM therapy to promote analgesia.

Chemically enhanced primary treatment of dairy wastewater using chitosan obtained from shrimp wastes: optimization using a Doehlert matrix design.

Dairy operations generate large volumes of polluted wastewater that require treatment prior to discharge. Chemically enhanced primary treatment (CEPT) is a widely utilized wastewater treatment strategy; but it requires the use of non-biodegradable coagulants that can lead to toxic-byproducts. In this study, chitin from shrimp shell waste is extracted and converted into chitosan. Chitosan was demonstrated to be a natural, low-cost alternative coagulant compatible with the CEPT. Following treatment, dissolved air flotation allowed for the removal of turbidity, COD, and UV254 from the synthetic dairy effluent (SDE). Doehlert matrix was used to optimize the chitosan dosage and pH of the CEPT; as well as to model the process. The mechanisms behind the coagulation-flocculation were revealed using zeta potential analysis. FTIR spectroscopy was utilized to confirm the functional groups present on the chitosan. Chitosan with a degree of deacetylation equal to 81% was obtained. A chitosan dose of 73.34 mg/L at pH 5.00 was found to be optimal for the removal of pollutants. Removals of COD, turbidity and UV254 were 77.5%, 97.6%, and 88.8%, respectively. The amount of dry sludge generated to treat 1 m³ of SDE was 0.041 kg. Coagulation-flocculation mechanisms involved in chitosan-mediated treatment of SDE involve the neutralization of electrostatic charges carried on the amine groups present in cationic chitosan at pH 5.00. Doehlert matrix proved to be a useful tool in optimizing parameters throughout the coagulation-flocculation process. Chitosan from shrimp waste is a low-cost, eco-friendly coagulant alternative for the removal pollutants from dairy effluent using the CEPT.

Mudanças de hábitos e saúde dos estudantes após ingresso na universidade / Changes in students daily habits and health after they start college

INTRODUÇÃO: O aumento de publicações sobre a vida do estudante do Ensino Superior demonstra o interesse crescente da comunidade científica sobre o tema. Tais estudos apontam para alterações na saúde dessa população após ingresso nesse nível de ensino. OBJETIVO: Investigar mudanças nos hábitos de vida dos estudantes que ingressam na universidade e o impacto em sua saúde física e mental. MÉTODOS: Foi adotada uma pesquisa qualitativa, com o uso de entrevista semiestruturada, aplicada em oito estudantes. Os dados foram analisados mediante análise de conteúdo, o que resultou em três categorias temáticas: Mudanças nos hábitos (alimentação, sono, atividades físicas, lazer e descanso); Impactos (físicos e mentais); Determinantes envolvidos na formação de novos hábitos (socioeconômicos, acadêmicos, familiares e afetivos e outros). RESULTADOS: A alimentação foi uma das dimensões que mais apresentou alterações, assim como o sono. Quanto aos impactos físicos, foram apontadas dores musculares, cefaleias tensionais, enxaquecas e agravamento de distúrbios, como gastrite. Nos impactos mentais, registrou-se os sintomas de estresse, cansaço, desmotivação e sentimentos de solidão, impotência, isolamento, desejo de desistir e agravamento de sofrimentos psíquicos já existentes, como depressão e ansiedade. Os determinantes mais frequentes foram os sociais, que abrangem as condições socioeconômicas dos estudantes, seguido dos educacionais, que abrangem o ambiente acadêmico. CONCLUSÃO: A experiência no Ensino Superior, neste caso, na universidade, provoca mudanças nos hábitos dos estudantes após ingresso, o que resulta em impactos em sua saúde e sugere a necessidade de se repensar as formas de seu funcionamento.

INTRODUCTION: The increasing number of publications about university students' lives reveals the growing interest that the scientific community holds in this theme. Such studies point to changes in the health of this population after entering this level of education. OBJECTIVE: The present study investigates changes in these students' daily habits after they start college and their impact on their physical and mental health. METHODS: A qualitative research was adopted, and semistructured interviews were applied to eight students. Data was verified using a content analysis technique, which resulted in three thematic categories: Habits variations (feeding, sleeping, physical activities practice, resting and leisure); life impacts (physical and mental); Determinants involved in these new habits acquisition (socioeconomic, academic, family and affective and others). RESULTS: Feeding and sleeping were dimensions that presented most transitions. The most common physical impacts were headache, migraine, muscle ache, and worsening of previous conditions such as gastritis. Regarding mental impacts, the following symptoms were registered: tiredness, stress, demotivation, loneliness, helplessness feelings, isolation, thoughts about giving up, and aggravation in previous psyche suffering as depression and anxiety. The noun determinants related to these changes were the social, which include the students' socioeconomic conditions, followed by the educational elements that comprehend the academic environment. CONCLUSION: A university's academic daily life generates multiple routine changes in their students, compromising their health. Therefore, restructuring universities organizations is needed.

Sex Differences in the Inflammatory Consequences of Stress: Implications for Pharmacotherapy.

Women are at significantly greater risk of developing stress-related disorders such as depression. The increased risk begins during puberty and continues throughout life until menopause, suggesting a role for ovarian hormones in this increased susceptibility. Importantly, inflammation has been gaining momentum in its role in the pathogenesis of depression. Herein, clinical and preclinical studies have been reviewed to better understand how sex differences within the immune system may contribute to exaggerated risk of depression in females. First, studies that investigate the ability of psychologic stress episodes to engage the inflammatory systems both in the brain and periphery are reviewed with a special focus on sex-specific effects. Moreover, studies are discussed that identify whether imbalanced inflammatory milieu contributes to the development of depression in males versus females and whether these effects are regulated by estradiol. Importantly, we propose a locus coeruleus-norepinephrine-cytokine circuit as a conduit through which stress could increase stress susceptibly in females. Finally, the anti-inflammatory capacity of traditional and nontraditional antidepressants is investigated, with the goal of providing a better understanding of pharmacotherapeutics to enhance strategies to personalize antidepressant treatments between the sexes. The studies reviewed herein strongly support the need for further studies to elucidate whether females are especially sensitive to anti-inflammatory compounds as adjuvants to traditional therapies. SIGNIFICANCE STATEMENT: Women have hve an increased risk of developing stress-related disorders such as depression. In this review, literature from clinical and preclinical studies are integrated to define sex differences in stress-induced inflammatory responses as a potential source for the etiology of sex differences in depressive disorders. Moreover, the anti-inflammatory capacity of traditional and nontraditional antidepressants is reviewed to inform on potential pharmacotherapeutic strategies to personalize antidepressant therapy in a sex-dependent manner.

Assessment and optimization of the use of a novel natural coagulant (Guazuma ulmifolia) for dairy wastewater treatment.

A feasible, novel, and natural coagulant extracted from G. ulmifolia stem bark was characterized and used in experiments of coagulation/dissolved air flotation (C/DAF) to treat synthetic dairy wastewater (SDW). The performance of G. ulmifolia to remove turbidity, chemical oxygen demand (COD), and UV254 was evaluated by using response surface methodology (Doehlert matrix). G. ulmifolia dosage and pH were evaluated and optimized in the C/DAF process and its characterization was performed by Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), and also zeta potential. Results showed that G. ulmifolia stem bark is composed of large quantities of condensed tannins represented by the groups C=C-C and CO of pyran (flavonoid C-rings), which serve as bridges during coagulation. Moreover, the presence of porous cavities in surface of G. ulmifolia, shown by SEM, indicated capacity for adsorption. G. ulmifolia dosage and pH were significant (p ≤ 0.05) for pollutant removal from the SDW. Jar test results revealed that 95.8% of turbidity, 76.0% of COD, 81.2% of BOD, and 85.6% of UV254 were removed from SDW by using G. ulmifolia stem bark at a dose of 775.8 mg L-1 and pH 5.00. Finally, our results showed promising use of G. ulmifolia as a coagulating agent due to its novelty, efficiency, low-cost, and eco-friendly properties as an alternative for the treatment of dairy wastewaters.

Predictive model for chloroform during disinfection of water for consumption, city of Montevideo.

The objective of this study was to predict chloroform formation resulting from the process of disinfecting water, particularly trihalomethane which is most frequently produced. A statistical model was used which included repeated measurements of water parameters used for monitoring water quality at 51 sites covering the municipal water system of Montevideo. Samples were taken considering different seasons from June 2009 to July 2011 in Montevideo. Total samples (n = 330) were analytically studied using the headspace-gas chromatography method coupled with mass spectrometry. Chloroform was the dependent variable and the covariables were pH, temperature, free chlorine, and total chlorine. A Tobit analysis with an unstructured correlation matrix was performed, and a significant interaction was found between pH and free chlorine for the prediction of chloroform formation. We concluded that parameters for the continuous control of water quality for consumption can be used to predict the levels of chloroform that may be present. Given the large measurement to variability found in the repeated measurements, the use of averages that include more than one season is not recommended to determine the degree of compliance with acceptable levels established by norms.

Anatomía de la arteria hepática: aspectos de interés en el trasplante hepático / Anatomy of hepatic artery: aspects of interest for hepatic transplant

Se disecaron 86 arterias hepáticas de cadáveres adultos valorando aquellos aspectos de su anatomía de interés en la cirugía del trasplante hepático. Los datos consignados fueron el número, origen, trayecto, topografía y terminación del o los pedículos arteriales del hígado, así como el calibre y la distancia al hilio hepático de cada uno de los potenciales sitios anastomóticos utilizados en el implante. Se comprobaron variaciones de la disposición normal de la arteria en 37 casos (36 por ciento) dentro de las cuales se destaca la presencia de una arteria hepática derecha accesoria en 12 casos (74 por ciento), una hepática izquierda en 6 casos (7 por ciento), ausencia de hepática propia en 11 casos (13 por ciento) y topografía retroportal en 1 caso (1,2 por ciento). Promedialmente se halló un calibre de 5 mm. a nivel de la hepática común y los sitios anastomóticos se situaron en un radio de 70 mm. a partir del hilio hepático. De la discusión de estos resultados se extraen conclusiones de aplicación práctica en los tiempos de ablación e implante del órgano.

¿Existe urgencia en quiste hidático de pulmón? / Should lung hydatid cyst be considered an urgency?

La ruptura del quiste hidático (QH) pulmonar puede provocar una hidatidosis secundaria (local, siembra bronquial, pleural secundaria). Es por ello que clásicamente se consideraba que un QH en sufrimiento era una urgencia quirúrgica. La experiencia ha demostrado que más peligroso que la ruptura, es operar un paciente con una neumonitis periquística. En el acto operatorio no se podrá realizar la broncorrafia desgarrando el parenquima pulmonar friable. Ello llevará a una aerostasis defectuosa, sangrado, reexpansión pulmonar incompleta, con el consiguiente peligro de complicaciones postoperatorias. Un enérgico tratamiento preoperatorio de la neumonitis es obligatorio no importando el estado de sufrimiento del quiste. La TAC no documentará el estado del pulmón. El objetivo de este trabajo es mostrar dos pacientes operados con una preparación correcta, donde se logró evitar complicaciones y un postoperatorio de pocos días. Por lo que concluimos que no se justifica una cirugía de urgencia, sin una preparación adecuada del parenquima pulmonar, con el fin de evitar la ruptura de un QH de pulmón