Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Echinocandin Treatment of Pneumocystis Pneumonia in Rodent Models Depletes Cysts Leaving Trophic Burdens That Cannot Transmit the Infection

Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express β -1,3-D-glucan synthetase and contain abundant β -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of β -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased β -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens

The ‘True’ Splenic Wanderer

Wandering spleen is an unusual entity and remains an elusive clinical diagnosis. Among the modern imaging modalities including computed tomography, magnetic resonance imaging, nuclear scans and ultrasonography, the latter appears to be the least invasive and the most effective in reaching a definitive diagnosis. A patient with ‘true’ wandering spleen who presented with chronic, intermittent abdominal pain, weight loss and a right lower quadrant mass that was interpreted as a pelvic lymphoma or a primary pelvic malignancy on computed abdominal tomography (CAT) scan is presented. Abdominal ultrasonography conducted a few weeks before the CAT scan showed a normal splenic shadow in the left upper abdomen

Nuclear expression of E-cadherin in solid pseudopapillary tumors of the pancreas.

CONTEXT: Solid pseudopapillary tumors of the pancreas are rare and have recently been shown to harbor mutations of the beta-catenin gene with resultant nuclear localization of beta-catenin protein to the nucleus. Moreover, there is a close relationship between beta-catenin and E-cadherin. OBJECTIVE: To explore the protein expression of E-cadherin in a series of solid pseudopapillary tumors of the pancreas. PARTICIPANTS: Eighteen cases of solid pseudopapillary tumors of the pancreas. DESIGN: The cases were studied using a tissue microarray that was constructed as follows: for each case, 4 to 14 cores measuring 1.0 mm each were drilled from the blocks. Tissue cores from normal pancreas were used as controls and for orientation purposes. MAIN OUTCOME MEASURES: The slides were stained with the following commercially available antibodies: CD10, CD56, vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, neuron-specific enolase, chromogranin, synaptophysin, beta-catenin and E-cadherin. RESULTS: All the tumors were CD10, vimentin, alpha-1-antitrypsin and alpha-1-antichymotrypsin diffusely positive (50% or more of the tumor cells staining) and CD56 showed focal positivity in all cases with 5-10% of tumor cells displaying immunolabeling. All cases were negative for chromogranin and synaptophysin. All 18 cases displayed cytoplasmic and nuclear localization of beta-catenin protein. Similarly, E-cadherin protein was localized to the nucleus in all 18 cases, with loss of the characteristic membranous decoration of cells. CONCLUSION: This study is the first demonstration of aberrant nuclear localization of E-cadherin protein in solid pseudopapillary tumors of the pancreas. Whilst the exact mechanism is not know and nuclear E-cadherin is not related to tumor aggression, this staining pattern may be of diagnostic value in concert with beta-catenin staining