The anti-nausea effects of CB1 agonists are mediated by an action at the visceral insular cortex

BACKGROUND AND PURPOSE

Conditioned gaping reactions reflect nausea-induced behaviour in rats. Cannabinoid 1 receptor (CB₁) agonists interfere with the establishment of nausea-induced conditioned gaping; however, it is not known if their effects are mediated by an action at peripheral or central CB₁ receptors.

EXPERIMENTAL APPROACH

We utilized the conditioned gaping model of nausea to evaluate the effect of peripheral and central administration of the peripherally restricted CB₁ agonist, CB13, on the establishment of LiCl-induced gaping in rats. We further evaluated the ability of HU-210 administered to the gustatory insular cortex (GIC) or visceral insular cortex (VIC) to interfere with LiCl-induced conditioned gaping and determined if this effect was mediated by CB₁ receptors.

KEY RESULTS

Central, but not peripheral, CB13 suppressed LiCl-induced conditioned gaping. Central administration of the potent CB₁ agonist, HU-210, delivered to the VIC, but not the GIC, suppressed the establishment of LiCl-induced gaping reactions, but not LiCl-induced suppression of hedonic reactions or conditioned taste avoidance. This pattern of results suggests that HU-210 delivered to the VIC prevented LiCl-induced nausea, but not learning per se. The suppression of LiCl-induced conditioned gaping by HU-210 was mediated by CB₁ receptors because it was prevented by co-administration of CB₁ antagonist/inverse agonist, AM-251, into the VIC. A high dose of AM-251 (20 µg) administered alone into the VIC did not produce conditioned gaping reactions.

CONCLUSIONS AND IMPLICATIONS

The nausea-relieving effects of CB₁ agonists, but not the nausea-inducing effects of CB₁ inverse agonists, are mediated, at least in part, by their action at the VIC in rats.     

Safety and Efficacy of Subcutaneous Parenteral Nutrition in Older Patients: A Prospective Randomized Multicenter Clinical Trial

Background: Many patients who cannot tolerate adequate enteral nutrition could benefit from parenteral nutrition support but fail to receive it due to difficult intravenous (IV) access. The objective of this study was to compare the safety and efficacy of subcutaneous (SC) administration of parenteral nutrition with the peripheral IV route. Materials and Methods: This was a prospective randomized multicenter study of 121 older hospitalized patients. The primary outcome was the composite end point of major local side effects, defined as local edema, blistering, erythema, phlebitis, cellulitis, unbearable pain, or route failure requiring a switch in route. Secondary outcomes were nutrition parameters, biochemical parameters, clinical outcomes, and safety. Results: The SC route (n = 59) was noninferior to the IV route (n = 61) for major local side effects. Major local side effects trended higher in the IV group (P = .059). Local edema was more common in the SC group (P < .05), while route failure was more common in the IV group (P < .001). Nutrition and biochemical parameters, safety, and clinical outcomes were similar between groups. Conclusions: The SC route of nutrient administration was better tolerated than the peripheral IV route. SC administration of parenteral nutrition represents a safe alternative to IV nutrition.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

Pain after barium enema: effect of CO2 and air on double-contrast study

One hundred fifty-one consecutive patients scheduled for double-contrast barium enema studies were assigned randomly to insufflation with either air or carbon dioxide (CO2) in a double-blind, prospective trial. Within 24 hours after the enema study, the patients were contacted by telephone by an interviewer, who completed a standard questionnaire. Radiographs from the enema studies were assessed for quality by two radiologists. Pain experienced after the procedure was graded from 0 (none) to 4 (severe). Clinically relevant (grades 2-4) pain was experienced by 30% of patients after insufflation with room air, compared with 11% of patients in whom CO2 was used for insufflation (P = .005). The mean pain score for CO2 was 0.4, and for room air, 1.2 (P less than .005). Although five patients experienced grade 4 pain after insufflation with air, no patient reported severe pain after CO2 insufflation. Post-evacuation films confirmed there was significantly less residual gas in the CO2 group. The quality of radiographs was equal in the two groups. CO2 has advantages for use in the double-contrast barium enema examination.     

Eugenol and its association with levodopa in 6‐hydroxydopamine‐induced hemiparkinsonian rats: Behavioural and neurochemical alterations

Parkinson's disease is a neurodegenerative disorder that affects the central nervous system and is mainly characterized by the loss of dopaminergic neurons and pro‐oxidant mechanisms. Eugenol has been widely studied due to its anti‐inflammatory and antioxidant activities, making it a promising neuroprotective agent. This study aimed to investigate the effects of eugenol and its combined action with levodopa in the 6‐hydroxydopamine‐induced Parkinson's disease model. Wistar rats were subjected to intrastriatal injection of 6‐hydroxydopamine (21 μg) and then treated with eugenol (0.1, 1, or 10 mg/kg), levodopa (25 mg/kg) or their combination (eugenol 10 mg/kg + levodopa 12.5 mg/kg) orally for 14 days. On the 14th day, the animals were subjected to behavioural tests, and after euthanization and dissection of the brain areas, neurochemical analyses were performed. The results showed that eugenol reduced the oxidative stress and behavioural disturbances induced by 6‐hydroxydopamine. The eugenol and levodopa combination was more effective in some behavioural parameters and body‐weight gain in addition to promoting an increase in reduced glutathione levels compared to levodopa alone. Thus, the neuroprotective activity of eugenol was observed against motor and neurochemical disorders. Additionally, the eugenol and levodopa combination was promising when compared to conventional treatment.     

Effect of Coffea canephora aqueous extract on microbial counts in ex vivo oral biofilms: a case study

In the present study, the ex vivo antimicrobial effect of brewed coffee was tested on oral biofilms. For this, unsweetened and sweetened (10 % sucrose) brewed light-roasted Coffea canephora at 20 % was used in biofilms formed by non-stimulated saliva from three volunteers. After 30 min contact with unsweetened and sweetened brews, the average microorganism count in the biofilms reduced by 15.2 % and 12.4 %, respectively, with no statistical difference among them. We also observed a drop of microorganisms in the biofilms after treatment with sucrose solution at 5 % compared to control (saline) and to sucrose at 1 % and 3 %. In conclusion, Coffea canephora extract reduces the microbial count in oral biofilm, and our data suggest that sucrose concentration in coffee brew can influence its antimicrobial property against the referred biofilm.     

Control of mother-to-child transmission of infectious diseases in Brazil: progress in HIV/AIDS and failure in congenital syphilis

In Brazil, syphilis and HIV infection are considered serious public health problems. However, in practice, epidemiological surveillance, prevention measures, and prenatal care seem to be more effective in the control of mother-to-child transmission of the HIV than in the control of transmission of the Treponema pallidum. Here we discuss the differences in surveillance, prenatal care, and care of the newborn. Important differences were identified. It is concluded that there is an urgent need to establish prevention of mother-to-child transmission of syphilis as a public health priority, using an integrated approach including women's health, children's health, primary health care, and STD/AIDS programs on all governmental levels. These issues also need to be discussed with all stakeholders involved. Important aspects related to the problem are the training of public health professionals, as well as the participation of the community. The elimination of congenital syphilis does not require expensive drugs, and diagnostic tools, but a long-term sustainable approach.     

Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.

PURPOSE: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. PATIENTS AND METHODS: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. RESULTS: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. CONCLUSION: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.