A Comparative Study on Platelet-Rich Plasma From Elderly Individuals and Young Adults to Treat Pressure Ulcers in Mice.

OBJECTIVE: The aim of the present study was to compare the therapeutic effects of activated platelet-rich plasma (PRP) prepared from elderly individuals and young adults to treat pressure ulcers (PUs), and to accumulate a theoretical basis for allogeneic PRP treatment of PUs in elderly patients. MATERIALS AND METHODS: Whole blood was extracted from elderly individuals aged >65 y and young adult volunteers for PRP preparation, and platelet concentrations in whole blood and PRP were compared. Growth factors released from activated PRP were assayed using the enzyme-linked immunosorbent assay. C57BL/6 mice were divided into three groups: the control saline, elderly-PRP (Group A), and young adult-PRP (Group B). Ischemia-reperfusion injury-induced PUs were established on the backs of mice. PUs were photographed on days 0, 5, and 10 to assess their sizes. Specimens were collected on day 10 and subjected to hematoxylin and eosin and Masson's staining. Immunohistochemical staining for CD31 was conducted to evaluate vascular formation, and cell invasion was assessed using a Transwell assay. The action of PRP on transforming growth factor-beta (TGF-ß)-dependent fibroblast activity and epithelial-mesenchymal transition was analyzed using immunofluorescence and Western blotting in vitro. RESULTS: The platelet concentrations in whole blood and PRP of young adults were significantly higher than that in elderly individuals. The two PRP treatment groups had similar platelet enrichment coefficients of PRP. After activation, PRP from young adults produced significantly higher levels of platelet-derived growth factor, TGF-ß, and vascular endothelial growth factor than PRP from elderly individuals (P < 0.05). The concentrations of platelet-derived growth factor, TGF-ß, and vascular endothelial growth factor were positively correlated with the platelet concentrations in whole blood and PRP. The effects of PRP in regulating the expressions of TGF-ß, α-smooth muscle actin, vimentin, and E-cadherin were observed in vivo and in vitro. The two PRP treatment groups exhibited better wound healing than the control group, as evidenced by more re-epithelialization, higher collagen content, skin fibrosis, and more blood vessel formation over time. Group B exhibited better wound healing than Group A (P < 0.05). CONCLUSION: PRP exhibits potent wound healing ability in PU therapy, and PRP from young adults is seemingly superior to that from elderly individuals because of a higher concentration of platelets and increased production of growth factors.

Systemic Loss of C-terminal Src Kinase Expression Elicits Spontaneous Suppurative Inflammation in Conditional Knockout Mice.

C-terminal Src kinase (Csk) is one of the critical negative regulators of the Src family of kinases. The Src family of kinases are nonreceptor tyrosine kinases that regulate inflammation, cell proliferation, motility, and adhesion. To investigate potential histologic lesions associated with systemic loss of Csk gene activity in adult mice, conditional Csk-knockout mice were examined. Cre-mediated systemic excision of Csk induced by tamoxifen treatment resulted in multiorgan inflammation. Specifically, induction of Csk gene excision with three days of tamoxifen treatment resulted in greater than 90% gene excision. Strikingly, these mice developed enteritis that ranged from minimal and suppurative to severe, fibrinonecrosuppurative and hemorrhagic. Other inflammatory lesions included suppurative pneumonia, gastritis, and myocarditis, and increased numbers of inflammatory cells within the hepatic parenchyma. When tamoxifen treatment was reduced from three days to one day in an effort to lower the level of Csk gene excision and limit lesion development, the mice developed severe suppurative to pyogranulomatous pneumonia and minimal to mild suppurative enteritis. Lesions observed secondary to Csk gene excision suggest important roles for Csk in downregulating the proinflammatory activity of the Src family of kinases and limiting neutrophil-mediated inflammation.

[DETERMINATION OF A FATTY ACIDS CONTENT IN BILIARY LIPIDS AS A PROGNOSTIC FACTOR FOR THE COMPLICATIONS OCCURRENCE IN PATIENTS AFTER OPERATIONS FOR AN ACUTE CHOLECYSTITIS IN A HIGH OPERATIVE­ANESTHESIOLOGICAL RISK].

Investigation was conducted with objective to establish a prognostic significance of the fatty acids content in biliary lipids for the complications occurrence in patients, operated on for an acute cholecystitis, while presence of high operative­anesthesiological risk. A fatty acids content in biliary lipids was analyzed in 64 patients in presence of moderate (grade ІІ) and severe (grade ІІІ) course of the disease. Coefficients К1 and К2 for prognostication of postoperative purulent­inflammatory complications occurrence were elaborated, their threshold level (К1=0.59, К2=1.8) was established. There was established, that excess of the threshold meaning of К1 and К2 in a bile of patients, suffering an acute cholecystitis while presence of high operative­anesthesiological risk, constitutes a prognostic criterion for the postoperative purulent­inflammatory complications occurrence

[Features of coagulative blood potential disorder in acute constitutional inflammatory response of septic tubo-ovarian formations].

BACKGROUND: There are no any systemized studies of relationship between the coagulative haemostasis' disorders and metabolic and cytokine status in patients with septic tuboovarial formations. OBJECTIVE: The aim of the present work was to study the mechanisms of blood coagulation disorders and their relationships with changes of cytokine status and acute phase of inflammatory response in septic tubo-ovarian formations in women. METHODS: 32 patients with purulent tubovarial formations and 30 healthy women were examined. RESULTS: Shortening of activated partial thromboplastin, prothrombin and thrombin clotting time, increasing the duration of XIIa-kallikrehin-dependent fibrinolysis, as well as the elevation of paracoagulation products in blood plasma were observed. IL-1ß (p =0.000023), TNF-α (p <0.001), C-reactive protein (p <0.001), haptoglobin (p <0.001) and fibrinogen (p <0.001) levels were higher in peripheral blood of patients in comparison with healthy women. Accumulation of lipid hydroperoxides (p <0. 001) and malonic dialdehyde (p <0.001) occurred in the blood plasma of patients. Serum albumin (p <0.001) and transferring (p <0.001) levels were lesser in patients with purulent tubo ovarial formations in comparison with healthy women. CONCLUSION: The obtained results showing an initiating role of cytokine and oxidative metabolic status changes in blood coagulation potential's and fibrinolysis activity's disorders developing. This biochemical signs may be used as objective criteria which may serve to determine the risk of thrombosis in case of acute inflammatory response in women with purulent inflammation.

Abscess penetration of cefpirome: concentrations and simulated pharmacokinetic profiles in pus.

PURPOSE: Abscess patients frequently receive antibiotic therapy when incision cannot be performed or in addition to incision. However, antibiotic concentrations in human abscesses are widely unknown. METHODS: Pharmacokinetics of cefpirome in 12 human abscesses located in different body regions was studied. Cefpirome (2 g) was administered as an intravenous short infusion, and concentrations were measured in plasma over an 8-h period and in abscesses at incision. A pharmacokinetic two-stage model was applied. RESULTS: At abscess incision performed 158 ± 112 min after the start of the infusion, the cefpirome concentrations in the abscess fluid varied markedly, ranging from ≤0.1 (limit of quantification) to 47 (mean 8.4 ± 14.1 ) mg/L. Cefpirome was detectable in nine of 12 abscesses. Maximum concentrations were calculated to be 183 ± 106 mg/L in plasma and 12 ± 16 mg/L in the abscess. A cefpirome concentration of 2 mg/L, which is the minimum concentration inhibiting growth of 90% of the most relevant bacterial pathogens, was exceeded spontaneously in six of 12 abscesses after a single dose. Cefpirome concentrations in the abscess did not correlate with either the pH or the ratio of surface area to volume of the abscesses, nor with plasma pharmacokinetics. CONCLUSIONS: Cefpirome may be useful to treat abscess patients because it was detectable in most abscesses after a single dose. However, the penetration of cefpirome into abscesses is extremely variable and cannot be predicted by measuring other available covariates.

[Structural changes in heart at experimental widespread purulent peritonitis].

Structural changes in the heart are studied at an experimental widespread purulent peritonitis. It was established that in 6 hours after initiation of peritonitis in a myocardium the severe disorders of blood circulation, interstitial edema, the phenomena of kariopyknosis, development of systemic toxic damages specifying in high speed at this disease were observed. One of the mechanism of their development is a energy deficiency. The proof of this is destructive changes of cardiomyocytes mitochondria. The comparative analysis of use of metabolic preparations "Citoflavin", containing amber acid, and "Neoton", containing phosphocreatine, for the purpose of pharmacological support of cardiac activity at an experimental widespread purulent peritonitis has revealed high efficiency of the preparation "Citoflavin". It caused more intensive decrease of inflammatory changes in a myocardium, preventing of cardiomyocytes necrobiosis, contribution to preservation of normal structure and growth of quantity of mitochondria.

[The role of interleukin 1-beta in pathogenesis and treatment of recurrent suppurative rhinosinusitis].

The objective of the present work was to study specific immunogenetic characteristics of 1-beta interleukin (IL 1-beta) production and estimate the possibility of using recombinant IL 1-beta for the treatment of recurrent suppurative rhinosinusitis. It was shown that the low production of IL 1-beta attributable to the combination of genotypes +3953>T *C/*C and -511C>T *C/*TAND *t/*t is associated with a relapse of suppurative rhinosinusitis. The patients presenting with this disorder are in need of dispensary examination and repeated administration of recombinant IL 1 beta (betaleukin) during the period of exacerbation of suppurative rhinosinusitis.

[Metabolic correction of the lipid-transport system in experimental diffuse purulent peritonitis].

The research was performed in 55 male chinchilla rabbits. For the first time the effect of metabolic preparations "citoflavin" and "neoton" of the protein-lipid spectrum of blood was studied in experimental diffuse purulent peritonitis. The development of diffuse purulent peritonitis caused negative changes in blood lipid-transport system which resulted in a decreased blood protein level and high density lipoproteins (HDL) and growth of triglycerides. In the HDL phospholipid spectrum the pathological changes are characterized by an increased lisophosphotide content and compensatory growth of the level of poliglycerophosphatides. A comparative analysis has shown that both preparations possess unidirectional action which is more pronounced in "citoflavin" than in "neoton".

Primary Ciliary Body Marginal Zone Lymphoma Presenting as Hemorrhagic Hypopyon.

PURPOSE: Our purpose is to report a patient with primary unilateral ciliary body marginal zone lymphoma who initially presented with hemorrhagic hypopyon. METHODS: Retrospective review of the clinical, imaging, and immunohistopathological features of the case was performed. RESULTS: A 59-year-old man was referred with right anterior uveitis of unknown etiology which was unresponsive to systemic treatment. Slit-lamp biomicroscopy showed normotensive hemorrhagic hypopyon in that eye. Anterior segment ultrasound biomicroscopy revealed an iridociliary mass lesion. Because an anterior chamber paracentesis was noncontributory, a diagnostic cyclectomy was performed. Histopathological evaluation showed that the neoplastic cells were positive for CD20, lambda light chain, and BCL 2. BCL 6, CD10, CD5, SOX11, kappa, and Cyclin D1 stains were negative. The final diagnosis was extranodal marginal zone lymphoma of the ciliary body. CONCLUSIONS: Although rare, ciliary lymphoma may be a cause of intractable anterior uveitis. Repeat biopsies could be carried out when there is a high level of clinical suspicion.

Pleural fluid interleukin-8 and C-reactive protein for discriminating complicated non-purulent from uncomplicated parapneumonic effusions.

BACKGROUND AND OBJECTIVE: This study was designed to test the hypothesis that measurement of IL-8 and CRP in pleural fluid could improve the identification of patients with non-purulent parapneumonic effusions that ultimately require chest tube drainage. METHODS: We assessed IL-8, CRP and three classical parameters (pH, glucose and LDH) in the pleural fluid of 100 patients with parapneumonic effusions. Forty-nine of these patients had non-purulent complicated effusions (complicated parapneumonic pleural effusion, CPPE), and 51 had uncomplicated parapneumonic pleural effusions (UPPE). Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid biochemical parameters for differentiating among the two patient groups. IL-8 production was determined using a commercially available ELISA kit, and CRP was measured by immunoassay. RESULTS: At a cutoff value of 1000 pg/mL, IL-8 differentiated CPPE from UPPE with a sensitivity of 84% and a specificity of 82%. Likewise, CRP levels were higher in CPPE than in UPPE, and showed 72% sensitivity and 71% specificity at a cutoff value of 80 mg/L. We found that all five pleural fluid tests showed similar diagnostic accuracies when evaluated by receiver-operating characteristic analysis. However, multivariate analysis indicated that the size of the effusion, as well as pleural fluid pH and IL-8 concentration, were the best discriminatory parameters, with likelihood ratios of 6.4, 4.4 and 3.9, respectively. CONCLUSIONS: Pleural fluid IL-8 is an accurate marker for the identification of non-purulent CPPE.