Increased levels of tissue corticosteroids are associated with important protective responses of critically ill patients. Critical illness and its treatment interfere with the normal corticosteroid response to illness and induce tissue corticosteroid insufficiency. Therefore, corticosteroid is commonly used in critically ill patients. In intensive care units, the main reasons for using steroids are critical illness-related corticosteroid insufficiency (CIRCI), septic shock, acute respiratory distress syndrome (ARDS), airway edema, etc. CIRCI may be suspected due to symptoms or signs such as unconsciousness, hemodynamic instability, fever, or electrolyte imbalance. An adrenocorticotropic hormone stimulation test or measurement of a random plasma cortisol level is necessary to diagnose CIRCI. Corticosteroid administration can be helpful when CIRCI is confirmed. Similar to CIRCI, corticosteroid can be used in septic shock. However, corticosteroid administration is not recommended for patients with sepsis without shock. The use of corticosteroid in patients with ARDS is still controversial. Although steroids are commonly used for critically ill patients, there are controversies related to the use of steroids in the intensive care unit. In this article, we review the physiology of the corticosteroid response to critical illness and practical issues relating to the diagnosis and treatment of corticosteroid insufficiency in critically ill patients.
Adrenal Cortex Hormones ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Critical Illness ; Diagnosis ; Edema ; Fever ; Hemodynamics ; Humans ; Hydrocortisone ; Intensive Care Units ; Physiology ; Plasma ; Respiratory Distress Syndrome, Adult ; Sepsis ; Shock ; Shock, Septic ; Steroids ; Unconsciousness

With the technological advances of mass spectrometry (MS)-based platforms, clinical proteomics is one of the most rapidly growing areas in biomedical research. Urine proteomics has become a popular subdiscipline of clinical proteomics because it is an ideal source for the discovery of noninvasive disease biomarkers. The urine proteome offers a comprehensive view of the local and systemic physiology since the proteome is primarily composed of proteins/peptides from the kidneys and plasma. The emergence of MS-based proteomic platforms as prominent bioanalytical tools in clinical applications has enhanced the identification of protein-based urinary biomarkers. This review highlights the characteristics of urine that make it an attractive biofluid for biomarker discovery and the impact of MS-based technologies on the clinical assessment of urinary protein biomarkers.
Biomarkers ; Kidney ; Mass Spectrometry* ; Physiology ; Plasma ; Proteome ; Proteomics*

This study was conducted to identify the effectiveness of platelet-rich plasma (PRP) and efficacy of intralesional injection as a method of application to acute cutaneous wounds in dogs. Healthy adult beagles (n = 3) were used in this study. Autologous PRP was separated from anticoagulant treated whole blood in three dogs. Cutaneous wounds were created and then treated by intralesional injection of PRP in the experimental group, while they were treated with saline in the control group on days 0, 2 and 4. The healing process was evaluated by gross examination throughout the experimental period and histologic examination on day 7, 14 and 21. In PRP treated wounds, the mean diameter was smaller and the wound closure rate was higher than in the control. Histological study revealed that PRP treated wounds showed more granulation formation and angiogenesis on day 7, and faster epithelialization, more granulation formation and collagen deposition were observed on day 14 than in control wounds. On day 21, collagen deposition and epithelialization were enhanced in PRP treated groups. Overall, PRP application showed beneficial effects in wound healing, and intralesional injection was useful for application of PRP and could be a good therapeutic option for wound management in dogs.
Animals ; Collagen/metabolism ; Dermis/cytology/injuries/physiology ; Dogs ; Epidermis/cytology/injuries/*physiology ; Female ; Granulation Tissue/cytology ; Injections, Intralesional/veterinary ; Male ; Neovascularization, Physiologic ; *Platelet-Rich Plasma ; Regeneration ; Treatment Outcome ; *Wound Healing ; Wounds and Injuries/therapy/*veterinary

OBJECTIVETo investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production.

METHODSThe microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured.

RESULTSCTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate.

CONCLUSIONSThe PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

Adenosine ; pharmacology ; Anticoagulants ; pharmacology ; Blood Platelets ; drug effects ; physiology ; Citrates ; pharmacology ; Citric Acid ; pharmacology ; Dipyridamole ; pharmacology ; Drug Combinations ; Glucose ; analogs & derivatives ; pharmacology ; Heparin ; pharmacology ; Platelet Activation ; drug effects ; Platelet-Rich Plasma ; Theophylline ; pharmacology ; Transforming Growth Factor beta1 ; metabolism

IgG4-related disease (IgG4-RD) is characterized by a systemic involvement of tumor-like lesions with IgG4-positive plasmacytes. We experienced a case of IgG4-RD developed in a patient with bronchial asthma (BA) and chronic rhinosinusitis (CRS). A 55-yr-old female patient with BA and CRS complained of both eyes and neck swelling as well as a recurrent upper respiratory infection in recent 1 yr. The serum levels of IgG4, creatinine, and pancreatic enzymes were elevated. A biopsy of the submandibular gland showed an abundant infiltration of IgG4-positive plasmacytes. Her symptoms remarkably improved after the treatment of a systemic steroid that has been maintained without recurrence. We report a rare case of IgG4-RD developed in a patient with BA and CRS.
Asthma/complications/*diagnosis ; Chronic Disease ; Creatinine/blood ; Female ; Humans ; Immunoglobulin G/*blood ; Middle Aged ; Pancreas/enzymology ; Plasma Cells/physiology ; Prednisolone/therapeutic use ; Republic of Korea ; Rhinitis/complications/*diagnosis/drug therapy ; Sinusitis/complications/*diagnosis/drug therapy ; Submandibular Gland/pathology ; Tomography, X-Ray Computed

Normal wound healing is a well-orchestrated process of inflammatory response, cell proliferation, and tissue remodeling. However, this orderly and precise process is impaired in chronic wounds. A series of complicated pathogenic factors, including enhanced inflammatory response, poor cell proliferation, restrained angiogenesis, restricted collagen deposition, and infection, contribute to the failure of healing of chronic wound. The application of platelet-rich plasma (PRP) has been explored as a treatment for chronic wounds as it can balance wound microenvironment for promoting wound healing. PRP can modulate the inflammatory mediators, growth factors, and cytokines, etc. to correct abnormal biological events and disorderly molecular environment of cell migration and proliferation, and thus promote wound healing appropriately. Yet, the mechanism of PRP in promoting healing of chronic wound is still not elaborated, and the clinical application of PRP needs to be standardized as soon as possible.
Cell Movement ; Cell Proliferation ; Chronic Disease ; Collagen ; Humans ; Platelet-Rich Plasma ; Severity of Illness Index ; Skin Ulcer ; metabolism ; pathology ; therapy ; Wound Healing ; physiology

Retinol-binding protein 4 (RBP4) is adipocyte-derived secreted adipokines and elevated RBP4 expression level was closely related to insulin resistance and type II diabetes mellitus. However, the exact mechanisms are unknown. To clarify the mechanism, RBP4 lentivirus particles were packaged to infect porcine preadipocytes. Then porcine preadipocytes were activated by insulin or induced model of insulin resistance. RBP4 interference efficiency and the gene expression of each treatment groups in PI3K/Akt pathways were examined by QRT-PCR and Western blotting. The result shows that RBP4 mRNA and protein expressions were suppressed more than 60% (P < 0.01). Furthermore, no matter under insulin stimulation or insulin resistance, RBP4 knockdown significantly increased the mRNA expressions of AKT2, PI3K, GLUT4 and IRS1 compared with the control. The protein phosphorylate levels of AKT2, PI3K, IRS1 arised, meanwhile enhanced the AKT2, PI3K, GLUT4 total protein expressions. Collectively, knockdown of RBP4 increased the insulin sensitivity through upregulated PI3K/Akt pathways related factors' expression and phosphorylation in porcine adipocytes. This research will provide a new idea to treat insulin resistance related diseases.
Adipocytes ; metabolism ; Animals ; Gene Knockdown Techniques ; Insulin Resistance ; physiology ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Retinol-Binding Proteins, Plasma ; genetics ; pharmacology ; Signal Transduction ; Swine

BACKGROUNDWhether plasma can transfer the protective effect(s) of remote ischemic preconditioning (RIPC) between animals remains unresolved. We therefore investigated the effects of plasma collected 48 hours after transient limb ischemia on blood pressure recovery during myocardial ischemia reperfusion (IR) in homogenic rats.

METHODSPlasma was collected from Lewis rats, and the donor rats were randomly assigned to 2 groups: transient limb ischemia and control (n = 8 each). Transient limb ischemia was achieved by four cycles of 5-minute ischemia and 5-minute reperfusion by noninvasive ligation and deligation of the both legs using elastic rubber bands after anesthesia. In the control group, no ligation was performed. Forty-eight hours later, whole blood was collected, and the plasma spun off. Study Lewis rats underwent 30-minute left anterior descending coronary artery occlusion followed by 180-minute reperfusion, and were randomly assigned to 2 groups (group A and group B, n = 24 each), each further subdivided into 3 subgroups (n = 8 each). The subgroups of group A received normal saline (group A1) , plasma of control rats (group A2), plasma of transient limb ischemia rats (group A3) respectively at 1 hour before IR; the subgroups of group B received normal saline (group B1), plasma of control rats (group B2), plasma of transient limb ischemia rats (group B3) respectively at 24 hours before IR. BIOPAC systems were used to measure hemodynamics of rats during myocardial ischemiareperfusion.

RESULTSSystolic blood pressure (SBP) after IR in group B3 was different from that in groups B1 and B2 (B3 vs. B1, P = 0.007; B3 vs. B2, P = 0.039) at the beginning of reperfusion and 30 minutes after reperfusion. SBP was higher in group B3 than in groups B1 and B2 at the beginning of perfusion (B3 vs. B1, P = 0.010; B3 vs. B2, P = 0.002) and 30 minutes after reperfusion (B3 vs. B1, P = 0.001; B3 vs. B2, P = 0.001). SBP did not differ among subgroups A1, A2 and A3. Diastolic blood pressure and heart rate did not change in group A or group B.

CONCLUSIONSThe transfusion of plasma collected 48 hours after transient limb ischemia into homogenic rats 24 hours before IR can improve the SBP recovery during reperfusion. This may suggest that cardioprotective effect of late phase of RIPC is transferable via plasma.

Animals ; Blood Pressure ; physiology ; Extremities ; blood supply ; Ischemia ; Ischemic Preconditioning ; Male ; Plasma ; Rats ; Rats, Inbred Lew ; Time Factors

PURPOSE: To overcome the potential disadvantages of the use of foreign materials and autologous fat or collagen, we introduce here an autologous plasma gel for injection laryngoplasty. The purpose of this study was to present a new injection material, a plasma gel, and to discuss its clinical effectiveness. MATERIALS AND METHODS: From 2 mL of blood, the platelet poor serum layer was collected and heated at 100degrees C for 12 min to form a plasma gel. The plasma gel was then injected into a targeted site; the safety and efficacy thereof were evaluated in 30 rats. We also conducted a phase I/II clinical study of plasma gel injection laryngoplasty in 11 unilateral vocal fold paralysis patients. RESULTS: The plasma gel was semi-solid and an easily injectable material. Of note, plasma gel maintains the same consistency for up to 1 year in a sealed bottle. However, exposure to room air causes the plasma gel to disappear within 1 month. In our animal study, the autologous plasma gel remained in situ for 6 months in animals with minimal inflammation. Clinical study showed that vocal cord palsy was well compensated for with the plasma gel in all patients at two months after injection with no significant complications. Jitter, shimmer, maximum, maximum phonation time (MPT) and mean voice handicap index (VHI) also improved significantly after plasma gel injection. However, because the injected plasma gel was gradually absorbed, 6 patients needed another injection, while the gel remained in place in 2 patients. CONCLUSION: Injection laryngoplasty with autologous plasma gel may be a useful and safe treatment option for temporary vocal cord palsy.
Adult ; Aged ; Aged, 80 and over ; Animals ; *Blood Platelets ; Female ; Humans ; Laryngoplasty/*methods ; Male ; Middle Aged ; Plasma/*physiology ; Rats

BACKGROUNDNeuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.

METHODSWe used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting.

RESULTSSNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.

CONCLUSIONSSNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1.

Amino Acid Transport System X-AG ; genetics ; metabolism ; Animals ; Disease Models, Animal ; GABA Plasma Membrane Transport Proteins ; Male ; Neuralgia ; genetics ; metabolism ; Neuroglia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Synaptic Transmission ; genetics ; physiology ; Synaptosomal-Associated Protein 25 ; genetics ; metabolism