The progression of pulmonary fibrosis (PF) entails a complex network of interactions between multiple classes of molecules and cells, which are closely related to the vagus nerve. Stimulation of the vagus nerve increases fibrogenic cytokines in humans, therefore, activation of the nerve may promote PF. The hypothesis was tested by comparing the extent and severity of fibrosis in lungs with and without vagal innervation in unilaterally vagotomized mice. The results show that in vagotomized lungs, there were less collagen staining, less severe fibrotic foci (subpleural, peri-vascular and peri-bronchiolar lesions) and destruction of alveolar architecture; decreased collagen deposition (denervated vs intact: COL1α1, 19.1 ± 2.2 vs 22.0 ± 2.6 ng/mg protein; COL1α2, 4.5 ± 0.3 vs 5.7 ± 0.5 ng/mg protein; p < 0.01, n = 21) and protein levels of transforming growth factor beta and interleukin 4; and fewer myofibroblast infiltration (denervated vs intact: 1.2 ± 0.2 vs 3.2 ± 0.6 cells/visual field; p < 0.05, n = 6) and M2 macrophages [though the infiltration of macrophages was increased (denervated vs intact: 112 ± 8 vs 76 ± 9 cells/visual field; p < 0.01, n = 6), the percentage of M2 macrophages was decreased (denervated vs intact: 31 ± 4 vs 57 ± 9%; p < 0.05, n = 5)]. It indicated that the vagus nerve may influence PF by enhancing fibrogenic factors and fibrogenic cells.
Hurt RT, Matheson PJ, Smith JW, Zakaria ER, Shaheen SP, McClain CJ, Garrison RN. Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol 303: G1144 -G1152, 2012. First published September 17, 2012 doi:10.1152/ajpgi.00278.2011.-Conventional resuscitation (CR) from hemorrhagic shock (HS) results in gut and liver hypoperfusion, organ and cellular edema, and vital organ injury. Adjunct direct peritoneal resuscitation (DPR) with dialysate prevents gut vasoconstriction, hypoperfusion, and injury. We hypothesized that DPR might also improve hepatocellular edema, inflammation, and injury. Anesthetized male SD rats were assigned to groups (n ϭ 8/group): 1) sham (no HS); 2) HS (40% MAP/60 min) ϩ intravenous fluid conventional resuscitation [CR; shed blood ϩ 2 vol saline (SAL)/30 min]; 3) HSϩCRϩDPR (30 ml ip 2.5% glucose dialysate); or 4) HSϩCRϩSAL (30 ml ip saline). Histopathology showed lung and liver injury in HSϩCR and HSϩCRϩSAL up to 24-h postresuscitation (post-RES) that was not in shams and which was prevented by adjunct DPR. Wet-to-dry weight ratios in HSϩCR revealed organ edema formation that was prevented by adjunct DPR. HSϩCR and HSϩCRϩSAL had 34% mortality by 24-h post-RES, which was absent with DPR (0%). Liver IFN-␥ and IL-6 levels were elevated in CR compared with DPR or shams. TNF-␣ mRNA was upregulated in CR/sham and DPR/sham. IL-17 was downregulated in DPR/sham. CXCL10 mRNA was upregulated in CR/sham but downregulated in DPR/sham. Despite restored central hemodynamic performance after CR of HS, liver blood flow was compromised up to 24 h post-RES, and the addition of DPR restores and maintains liver perfusion at 24-h post-RES. DPR prevented liver injury, histological damage, and edema formation compared with CR alone. DPR provided a mitigating anti-inflammatory dampening of the systemic inflammatory response. In all, these effects likely account for improved survivorship in the DPR-treated group. hemorrhagic shock; liver blood flow; liver injury DESPITE ADVANCES IN TREATMENT and therapies, hemorrhagic shock (HS) remains a major cause of morbidity and mortality following trauma in the United States (18). The clinical role the liver plays during HS and in subsequent multiple organ failure (MOF) is unclear. The largest and most recent clinical study followed 1,962 trauma patients with injury severity score Ͼ 14 (ISS Ͼ14) during a 3-year period (17). Of the patients who met the study's inclusion criteria, 154 (7.9%) exhibited signs of liver dysfunction during their hospital course. In general, these patients with liver dysfunction were older and had higher injury severity scores and lower prehospital blood pressure (17). Patients who developed high serum levels of bilirubin, a serum marker of liver injury, had longer stays in the intensive care unit and higher mortality (16.2% vs. 2.5%) compared with patients with normal or slightly elevated bilirubin. While these observational...
The immunosecretory disorders are a diverse group of diseases associated with proliferation of an abnormal clone of immunoglobulin (Ig)-synthesizing, terminally differentiated B cells. These disorders include multiple myeloma (MM) and its variants, plasmacytoma, Waldenstrom macroglobulinemia, monoclonal gammopathy of undetermined significance, and monoclonal Ig deposition diseases, the latter including primary amyloidosis and nonamyloidotic types. These disorders are histologically composed of plasma cells, or plasmacytoid cells which produce Ig that is synthesized and usually secreted and can be deposited in some diseases. The Ig can be complete or can be composed of either heavy or light chains and is termed M-(monoclonal) protein. In MM, this proliferation overwhelms the normal cellular counterparts that synthesize and secrete appropriate levels of Ig. Immunosecretory disorders have been classified in multiple schemes, mostly morphologic, to such a degree that the classification of these entities has become a challenge to pathologists. The World Health Organization classification in 2001 was helpful because it provided specific clinicopathologic criteria for diagnosis. However, terms such as "progressive" disease were not well defined. In 2003, the International Myeloma Group defined MM as a disease with related organ and tissue injury, serving to better explain progressive in terms of deterioration of organ (renal, bone, and bone marrow) function over time. Therefore, modern classification of immunosecretory diseases is based on integration of clinical, morphologic, laboratory, radiographic, and biologic (including molecular) parameters, which we review here.
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