Inhibition of serotonergic signaling induces higher consumption of both sucrose solution and toxic baits in carpenter ants

Biogenic amines play an important role in the regulation of appetitive responses in insects. Among them, serotonin (5-HT) regulates feeding-related processes in numerous insect species. In carpenter ants, 5-HT administration has been shown to depress feeding behavior, thus opening the possibility of using 5-HT modulation in control strategies against those species considered as pest. Here we studied if administration of a 5-HT antagonist, ketanserin, promotes feeding of a sucrose solution and a toxic bait in carpenter ants Camponotus mus. We found that 3 h after a single oral administration of ketanserin, the mass of sucrose solution consumed by carpenter ants increased significantly. A similar effect was found after a chronic administration that lasted 5 days. Yet, ketanserin did neither affect the intake rates nor the activity of the pharyngeal pump that mediates feeding dynamics. In addition, ketanserin promoted the consumption of a toxic bait based on boric acid. Our results thus show that feeding motivation and consumption of both sucrose solution and a toxic bait can be enhanced via prior administration of ketanserin. We discuss the possible mechanisms underlying these effects and conclude that understanding basic physiological and neural principles that underlie feeding motivation allows establishing more efficient control strategies for pest insects.

Neuropeptide Y Reduces Social Fear in Male Mice: Involvement of Y1 and Y2 Receptors in the Dorsolateral Septum and Central Amygdala

Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We previously showed that intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC) and localized these effects to the dorsolateral septum (DLS) and central amygdala (CeA). In the present study, we aimed to identify the receptor subtypes that mediate these local effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduced the expression of SFC-induced social fear in a brain region- and receptor-specific manner in male mice. In the DLS, NPY reduced the expression of social fear by acting on Y2 receptors but not on Y1 receptors. As such, prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 μL/side) but not the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 μL/side) blocked the effects of NPY in the DLS. In the CeA, however, BIBO3304 trifluoroacetate but not BIIE0246 blocked the effects of NPY, suggesting that NPY reduced the expression of social fear by acting on Y1 receptors but not Y2 receptors within the CeA. This study suggests that at least two distinct receptor subtypes are differentially recruited in the DLS and CeA to mediate the effects of NPY on the expression of social fear.

Does prior administration of rtPA influence acute ischemic stroke clot composition? Findings from the analysis of clots retrieved with mechanical thrombectomy from the RESTORE registry

Background and purpose There is still much debate whether bridging-therapy [intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT)] might be beneficial compared to MT alone. We investigated the effect of IVT on size and histological composition of the clots retrieved from patients undergoing bridging-therapy or MT alone. Methods We collected mechanically extracted thrombi from 1000 acute ischemic stroke (AIS) patients included in RESTORE registry. Patients were grouped according to the administration (or not) of IVT before thrombectomy. Gross photos of each clot were taken and Extracted Clot Area (ECA) was measured using ImageJ software. Martius Scarlett Blue stain was used to characterize the main histological clot components [red blood cells (RBCs), fibrin (FIB), platelets/other (PTL)] and Orbit Image Analysis was used for quantification. Additionally, we calculated the area of each main component by multiplying the component percent by ECA. Chi-squared and Kruskal–Wallis tests were used for statistical analysis. Results 451 patients (45%) were treated with bridging-therapy while 549 (55%) underwent MT alone. When considering only percent histological composition, we did not find any difference in RBC% (P = 0.895), FIB% (P = 0.458) and PTL% (P = 0.905). However, bridging-therapy clots were significantly smaller than MT-alone clots [32.7 (14.8–64.9) versus 36.8 (20.1–79.8) mm2, N = 1000, H1 = 7.679, P = 0.006*]. A further analysis expressing components per clot area showed that clots retrieved from bridging-therapy cases contained less RBCs [13.25 (4.29–32.06) versus 14.97 (4.93–39.80) mm2, H1 = 3.637, P = 0.056] and significantly less fibrin [9.10 (4.62–17.98) versus 10.54 (5.57–22.48) mm2, H1 = 7.920, P = 0.005*] and platelets/other [5.04 (2.26–11.32) versus 6.54 (2.94–13.79) mm2, H1 = 9.380, P = 0.002*] than MT-alone clots. Conclusions Our results suggest that previous IVT administration significantly reduces thrombus size, proportionally releasing all the main histological components.

Systemic Administration of Tempol Attenuates the Cardiorespiratory Depressant Effects of Fentanyl

Fentanyl is a high-potency opioid receptor agonist that elicits profound analgesia and suppression of breathing in humans and animals. To date, there is limited evidence as to whether changes in oxidant stress are important factors in any of the actions of acutely administered fentanyl. This study determined whether the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), or a potent antioxidant, N-acetyl-L-cysteine methyl ester (L-NACme), modify the cardiorespiratory and analgesic actions of fentanyl. We examined whether the prior systemic injection of Tempol or L-NACme affects the cardiorespiratory and/or analgesic responses elicited by the subsequent injection of fentanyl in isoflurane-anesthetized and/or freely moving male Sprague-Dawley rats. Bolus injections of Tempol (25, 50 or 100 mg/kg, IV) elicited minor increases in frequency of breathing, tidal volume and minute ventilation. The ventilatory-depressant effects of fentanyl (5 μg/kg, IV) given 15 min later were dose-dependently inhibited by prior injections of Tempol. Tempol elicited dose-dependent and transient hypotension that had (except for the highest dose) resolved when fentanyl was injected. The hypotensive responses elicited by fentanyl were markedly blunted after Tempol pretreatment. The analgesic actions of fentanyl (25 μg/kg, IV) were not affected by Tempol (100 mg/kg, IV). L-NACme did not modify any of the effects of fentanyl. We conclude that prior administration of Tempol attenuates the cardiorespiratory actions of fentanyl without affecting the analgesic effects of this potent opioid. As such, Tempol may not directly affect opioid-receptors that elicit the effects of fentanyl. Whether, the effects of Tempol are solely due to alterations in oxidative stress is in doubt since the powerful antioxidant, L-NACme, did not affect fentanyl-induced suppression of breathing.

Signaling in Rat Brainstem via Gpr160 is Required for the Anorexigenic and Antidipsogenic Actions of Cocaine- and Amphetamine-Regulated Transcript Peptide

Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp's ability to reduce food and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacologic dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food and water intakes. Blockade of Gpr160 in the 4V, independent of pharmacologic CART treatment, caused an increase in both overnight food and water intakes. The decrease in food, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a GLP-1 receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and non-neuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection, and extend these findings to water drinking. Gpr160ir was observed in both neuronal and non-neuronal cell types in regions known to be important in the multiple pharmacologic effects of CARTp, identifying those areas as targets for future compromise of function studies.

Recovery of COVID-19 acute respiratory distress syndrome with tocilizumab: successful outcome in two critically ill patients

Background: Severe pneumonia and acute respiratory distress syndrome (ARDS) due to COVID-19 is a challenge for nowadays medical practice. Although there is no clarity in the principal mechanism of lung damage and ARDS development, it has been suggested that one of the main reasons of this pathology is the hyperactivation of the immune system, better known as cytokine storm syndrome. Tocilizumab has been proposed to treat COVID-19 severe cases associated to ARDS. Results & methodology: Here we present two successful cases of tocilizumab administration in two COVID-19 patients with prior administration of antiviral therapy (hydroxychloroquine, azithromycin, lopinavir and ritonavir) with adequate response and resolution of ARDS, septic shock and severe pneumonia within the first 72 h. Discussion & conclusion: This case supports the usage of tocilizumab as an effective therapy in COVID-19 associated cytokine storm syndrome. Further studies should be done in order to assess its effectiveness and security.

The Challenges of Melanoma during COVID-19 Pandemic

Diagnosis, tratament and follow-up of patients with melanoma during COVID-19 pandemic is quite challenging. These patients are often immunocompromised, but, on the other hand, management of this malignant skin cancer should not be delayed. It is necessary to diagnose and stage the melanoma as soon as possible, in an attempt to provide a better prognosis. There are few data regarding the treatament of melanoma during COVID-19 pandemia. However, the general recommandations suggest testing all cancer patients prior administration of the therapy. The European Society for Medical Oncology (ESMO) provided guidelines regarding therapy of this skin cancer during COVID-19 pandemic. Every patient is different, and it is always important to evaluate the risks and benefi ts.

Injection ranitidine induced death

Ranitidine is a histamine-2-receptor antagonist. It was a commonly used drug. It holds excellent safety record. Anaphylactic reactions to ranitidine is uncommonly encountered. Death due to ranitidine is extremely a rare event and very few cases are reported world-wide. Clinical history, Lab investigations and histological data of a 43-Years old woman with negative history of allergic events, who died suddenly after the intra-venous administration of 50mg of intravenous ranitidine which was prescribed as a routine pre medication prior hysterectomy is presented below. Though the incidence of anaphylactic reactions is less with ranitidine, precautions to be taken prior administration of the drug and when such an event is encountered it should be promptly managed.

Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER (JCOG1804E)

One of the standard treatments of resectable esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemotherapy followed by surgery. Nivolumab showed efficacy for metastatic ESCC. However, the safety and efficacy of neoadjuvant nivolumab with chemotherapy for ESCC is unknown. Therefore, we will conduct FRONTiER to evaluate the safety and efficacy of nivolumab adding to neoadjuvant chemotherapy. FRONTiER comprises four experimental cohorts: (A) including nivolumab plus 5-FU+CDDP (cisplatin and 5-fluorouracil [CF]); (B) including one prior administration of nivolumab and the cohort A regimen; (C) including nivolumab plus docetaxel+ CF; (D) including one prior administration of nivolumab and the cohort C regimen; an expanded cohort. The primary end point is the incidence of dose-limiting toxicities from the initial dose to the 30th postoperative day. Clinical Trial Identifier: NCT03914443