Dendritic morphology of neurons in prefrontal cortex and ventral hippocampus of rats with neonatal amygdala lesion

Neonatal basolateral amygdala (nBLA) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Recently, we reported that nBLA lesions result in significant decreases in the dendritic spine number of layer 3 prefrontal cortex (PFC) pyramidal cells and medium spiny neurons of the nucleus accumbens (NAcc), which all changes after puberty. At present, we aimed to evaluate the effect of this lesion in pyramidal neurons of CA1 of the ventral hippocampus (VH) and layer 5 of the PFC. In order to assess the effects of nBLA lesions on the dendritic morphology of the PFC and VH neurons, we carried out nBLA lesions in rats on postnatal day (PD) 7, and then we studied the dendritic morphology of these two limbic subregions at prepubertal (PD35) and postpubertal (PD60) ages. Dendritic characteristics were measured by Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of nBLA lesions on the prepulse inhibition (PPI) and acoustic startle responses. The nBLA lesion induced a significant increase in dendritic length of layer 5 pyramidal neurons of the PFC at both ages, with a decrease in the dendritic spines density after puberty. The spine density of CA1 VH pyramidal neurons showed significant decreases at both ages. PPI was decreased in adulthood in the animals with an nBLA lesion. These results show that an nBLA lesion alters the dendritic morphology at the level of the PFC and VH in distinct ways before puberty, suggesting a disconnection between these limbic structures at an early age, and increasing our understanding of the implications of the VH in early amygdala dysfunction in schizophrenia.     

Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles

The incorporation of nanoparticles (NPs) in industrial and biomedical applications has increased significantly in recent years, yet their hazardous and toxic effects have not been studied extensively. Here, we studied the effects of 24 nm silver NPs (AgNPs) on a panel of bacteria isolated from medical devices used in a hospital intensive care unit. The cytotoxic effects were evaluated in macrophages and the expression of the inflammatory cytokines IL-6, IL-10 and TNF-α were quantified. The effects of NPs on coagulation were tested in vitro in plasma-based assays. We demonstrated that 24 nm AgNPs were effective in suppressing the growth of clinically relevant bacteria with moderate to high levels of antibiotic resistance. The NPs had a moderate inhibitory effect when coagulation was initiated through the intrinsic pathway. However, these NPs are cytotoxic to macrophages and are able to elicit an inflammatory response. Thus, beneficial and potential harmful effects of 24 nm AgNPs on biomedical devices must be weighed in further studies in vivo. From the Clinical Editor: The authors of this study demonstrate that gallic acid reduced 24 nm Ag NPs are effective in suppressing growth of clinically relevant antibiotic resistant bacteria. However, these NPs also exhibit cytotoxic properties to macrophages and may trigger an inflammatory response. Thus, the balance of beneficial and potential harmful effects must be weighed carefully in further studies.     

How Do I Empathize With You? Let Me Count the Ways: Relations Between Facets of Pain-Related Empathy

This study examined the extent to which components of empathy (ie, empathic accuracy, empathic tendencies, and empathic responses) were correlated within the context of chronic pain couples. Additionally, the interrelationships between these empathy variables and spouse responses to pain were investigated. Participants were 57 couples in which at least 1 spouse reported chronic musculoskeletal pain. Each couple participated in a videotaped interaction about the impact of pain in their lives together, after which they completed an empathic accuracy procedure. The interactions were coded for the spouse's use of empathic responses. Couples also completed surveys about pain severity, pain interference, empathic tendencies, marital satisfaction, and perceived spousal responses (ie, solicitous and punishing responses) to pain. Spousal empathic responses and empathic accuracy were not related to one another nor were they related to spousal empathic tendencies, or solicitous spouse responses. Spousal punishing responses were negatively related to empathic responses. The association between solicitousness and empathic responses was moderated by spousal marital satisfaction. The findings suggest that there are not clear associations among these empathy variables. The results also indicate that the climate in which solicitousness is provided may influence the extent to which spouses display empathic responses. PERSPECTIVE: The findings have implications for models of pain empathy and suggest that future research is needed to understand relations between aspects of empathy. Moreover, interventions aimed at addressing the empathic climate in which support is delivered may help spouses more empathically and effectively communicate with and assist partners with pain management.     

Clinical challenges in a patient with dabigatran-induced fatal hemorrhage

ObjectiveTo report clinical challenges in managing dabigatran-induced bleeding.MethodsA 78-year-old woman came to the hospital with severe coagulopathy, respiratory failure, hypotension, and bleeding secondary to dabigatran therapy. At admission, creatinine clearance was 15 mL/min; prothrombin time, 147.5 seconds; activated partial thromboplastin time, >200 seconds; and international normalized ratio, 12.42. Medications taken at home included dabigatran, 150 mg BID. During the hospitalization, multiple blood product transfusions were given, vitamin K and prothrombin complex concentrate were administered, and dialysis was initiated in an attempt to achieve hemostasis. Despite multiple interventions, coagulopathy persisted (prothrombin time, 70.8 seconds; activated partial thromboplastin time, >200 seconds; and international normalized ratio, 6.05), with continued bleeding. On hospital day 5, the patient died.ConclusionsAccording to the Naranjo probability scale, bleeding associated with dabigatran revealed a probable relationship. This fatal case illustrates our concern about the usefulness of currently recommended anticoagulation laboratory tests and of the efficacy of blood transfusion, dialysis, and prothrombin complex concentrate in managing life-threatening bleeding secondary to dabigatran. In addition, clinicians should be cognizant of the renal recommendations for the newer oral anticoagulant agents to prevent potentially catastrophic results.     

Role of ghrelin in the pathophysiology of eating disorders: implications for pharmacotherapy

Ghrelin is the only known circulating orexigenic hormone. It increases food intake by interacting with hypothalamic and brainstem circuits involved in energy balance, as well as reward-related brain areas. A heightened gut-brain ghrelin axis is an emerging feature of certain eating disorders such as anorexia nervosa and Prader-Willi syndrome. In common obesity, ghrelin levels are lowered, whereas post-meal ghrelin levels remain higher than in lean individuals. Agents that interfere with ghrelin signalling have therapeutic potential for eating disorders, including obesity. However, most of these drugs are only in the preclinical phase of development. Data obtained so far suggest that ghrelin agonists may have potential in the treatment of anorexia nervosa, while ghrelin antagonists seem promising for other eating disorders such as obesity and Prader-Willi syndrome. However, large clinical trials are needed to evaluate the efficacy and safety of these drugs.     

Advanced glycation endproduct changes to Bruch's membrane promotes lipoprotein retention by lipoprotein lipase

Lipoprotein particles accumulate in Bruch's membrane before the development of basal deposits and drusen, two histopathologic lesions that define age-related macular degeneration (AMD). We therefore, sought to determine which molecules could participate in lipoprotein retention. Wild-type or lipoprotein lipase-deficient mice were injected with low-dose D-galactose or PBS subcutaneously for 8 weeks to induce advanced glycation endproduct (AGE) formation. Some mice were also injected with the AGE breaker phenacylphiazolium bromide and D-galactose. Rhodamine-labeled low-density lipoproteins were injected into mice, and the fluorescence was measured up to 72 hours later. AGEs, proteoglycans, and other lipid-retaining molecules were evaluated by IHC. Lipoprotein lipase distribution was assessed in AMD samples by IHC. D-galactose-treated mice retained lipoproteins in the retinal pigment epithelial and Bruch's membrane to a greater extent than either PBS- or phenacylphiazolium bromide/D-galactose-treated mice at 24 and 72 hours after injection (P ≤ 0.04). Immunolabeling for carboxymethyllysine, biglycan, and lipoprotein lipase was found in D-galactose-treated mice only. Mice deficient for lipoprotein lipase treated with D-galactose did not retain lipoproteins to any measureable extent. Human AMD samples had lipoprotein lipase labeling within drusen, basal deposits, and the choroid. Mice treated with D-galactose to induce AGE formation in Bruch's membrane retain intravenously injected lipoproteins. Our results suggest that lipoprotein retention in Bruch's membrane is mediated by lipoprotein lipase.     

Effect of aging and oxidative stress on elongation factor-2 in hypothalamus and hypophysis

The hypothalamic-hypophysis system (HHS) secretes peptide hormones whose synthesis requires the integrity of the translation machinery. As the organisms age, a considerable diminution of the protein synthesis takes place in several tissues. Among the possible causes of the decline of translation in old animals are the modifications of elongation factor-2 (eEF-2). We studied whether the level of this protein was affected in the HHS in old animals. The effects of aging are compared to those of an oxidant compound (cumene hydroperoxide) administered to young rats. The results indicate that oxidative stress could be involved in the alterations of eEF-2, which forms adducts with malondialdehyde (MDA) and 4-hydroxynonenal (HNE). The alterations of eEF-2 levels, secondary to lipid peroxidation and adduct formation with these aldehydes could contribute to the suboptimal hormone production from these tissues during aging. Besides eEF-2, proteomic analysis shows that several other proteins are affected.     

Evaluation of three automated systems for susceptibility testing of enterobacteria containing qnrB, qnrS, and/or aac(6')-Ib-cr

The accuracy of the MicroScan WalkAway, BD Phoenix, and Vitek-2 systems for susceptibility testing of quinolones and aminoglycosides against 68 enterobacteria containing qnrB, qnrS, and/or aac(6 ')-Ib-cr was evaluated using reference microdilution. Overall, one very major error (0.09%), 6 major errors (0.52%), and 45 minor errors (3.89%) were noted.     

Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases in Spain: microbiological and clinical features

Extended-spectrum β-lactamases (ESBL) of the CTX-M, SHV, and TEM families were recognized in 76 (67%), 31 (27%), and 6 (5%) isolates, respectively, among 162 ESBL-producing Klebsiella pneumoniae (ESBL-Kp) strains obtained in a multicenter study in Spain. Predisposing factors for ESBL-Kp acquisition included invasive procedures, mechanical ventilation, and previous antimicrobial use.