Yavuz Beyazit

Assessment of neutrophil-lymphocyte ratio in ulcerative colitis: A promising marker in predicting disease severity

BACKGROUND AND AIM In order to diagnosis and monitor the disease activity of ulcerative colitis (UC), serum biomarkers are generally used, but none of them are specific for intestinal inflammation. It is therefore desirable in clinical practice to be able to assess disease activity with simple, inexpensive and objective tools. The objective of the present study was to assess whether the neutrophil-lymphocyte ratio (NLR) would be useful in predicting disease severity in UC patients who had not received corticosteroid or immunosuppressive drugs within a defined period of time. Additionally, a possible relationship of NLR with other inflammatory markers in UC patients was also investigated. METHODS We designed a retrospective study examining the utility of NLR in estimating disease severity in UC patients admitted to our hospital between 2008 and 2011. In total, 119 patients with active UC and 77 patients with inactive UC were enrolled in the study group, and 59 age and gender matched healthy subjects were included as the control group. Disease activity was assessed using Truelove and Witts criteria. RESULTS In the active UC group, NLR values were found to be elevated compared to inactive UC patients and controls (3.22 ± 1.29, 1.84 ± 0.69 and 2.01 ± 0.64, respectively). Using ROC statistics, a cut-off value of 2.16 indicated the presence of active disease with a sensitivity of 81.8% and a specificity of 80.5% (positive predictive value [PPV] 86.8%, negative predictive value [NPV] 73.8%). NLR values were found to be correlated with WBC and ESR levels. CONCLUSIONS The present study revealed that NLR is increased in active UC. Peripheral blood NLR can reflect disease activity and can be used as an additional marker for estimating intestinal inflammation.

Mean platelet volume as an indicator of disease severity in patients with acute pancreatitis.

AIM Acute pancreatitis (AP) constitutes a systemic inflammatory process which is often accompanied by thrombosis and bleeding disorders. The role of platelets in the pathophysiology of the disease has not been elucidated yet. Mean platelet volume (MPV) is an index of platelet activation and reported to be influenced by inflammation. The objective of the present study is to assess whether platelet volume would be useful in predicting disease severity in AP. Additionally possible relationship of MPV with clinical and radiologic parameters in conjunction with other inflammatory markers during AP was also investigated. PATIENTS AND METHODS A total of 144 AP patients (male/female: 87/57), and 40 healthy subjects (male/female: 23/17) were enrolled in this study. Mean platelet volume and inflammatory parameters were measured for all study participants. Modified Glasgow Prognostic Score (mGPS) and the computerized tomography severity index (CTSI) were used as to predict the disease severity in AP patients. RESULTS A statistically significant decrease in MPV levels was observed in AP patients (8.06 ± 0.71 fL) compared with healthy controls (8.63 ± 0.62 fL) (P<0.001). According to the mGPS, overall accuracy of MPV in determining severe AP was 72.7% with a sensitivity, specificity, NPV and PPV of 70.6%, 73.9%, 81.9%, and 60 respectively (AUC: 0.762). Overall accuracy of MPV in predicting disease severity according to CTSI was not superior compared with other inflammation markers. CONCLUSION The present study demonstrated that MPV is decreased in AP. Assessment of MPV with other inflammatory markers may provide additional information about disease severity in AP.

Pathobiological aspects of the local bone marrow renin–angiotensin system: a review

The local haematopoietic bone marrow (BM) renin—angiotensin system (RAS) mediates pathobiological alterations of haematopoiesis in an autocrine/paracrine/intracrine fashion. Recent data further indicated the existence of angiotensin-converting enzyme (ACE) in human primitive lympho-haematopoietic cells, embryonic, foetal and adult haematopoietic tissues. Human umbilical cord blood cells also express renin, angiotensinogen, and ACE mRNAs. As ACE and other angiotensin peptides function in human haematopoietic stem cells (HSCs) throughout haematopoietic ontogeny and adulthood, local RAS could also have a function in HSC plasticity, and the development of haematological neoplastic disorders. The presence of ACE on leukaemic blast cells within leukaemic BM, on erythroleukaemic cells, ACE-expressing macrophages in lymph nodes of Hodgkin disease, renin activity in leukaemic blasts, angiotensin II as an autocrine growth factor for AML, increased renin gene activity during NUP98-HOXA9 enhanced blast formation, higher levels of BB9/ACE (+) AML isoforms, and altered JAK-STAT pathway as a link between RAS and leukaemia indicated the wide pathobiological aspects of local BM RAS. The comparable biological actions of local RASs throughout the human body (including myocardium, pancreas, pituitary gland, ovary and kidney) represent the true basis for the search of their prominence in tissue functions. Recent data and perspectives of the local BM RAS in health and disease are reviewed in this paper.

Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis.

BACKGROUND AND AIMS Liver biopsy is the gold standard procedure for documenting liver damage in chronic hepatitis C (CHC), as for many other chronic liver diseases. Mean platelet volume (MPV) is a laboratory marker obtained from complete blood count (CBC) analysers in routine clinical practice. The goal of the present study was to evaluate whether MPV would be useful in predicting liver histologic severity in CHC. PATIENTS AND METHODS A total of 59 patients with CHC and 25 control subjects were recruited into the present study. There were 26 men and 33 women in the CHC group and 12 men and 13 women in the control group. MPV was recorded at the time of admission. The clinical characteristics of CHC patients, including demographics, laboratory and liver biopsy findings, were reviewed. RESULTS A statistically significant increase in MPV values was observed in CHC patients (8.54 ± 0.63 fL) compared to healthy controls (7.65 ± 0.42 fL) (P < 0.001). Moreover, MPV values were significantly higher among patients with advanced fibrosis as compared to those with mild fibrosis (8.99 ± 0.57 fL vs. 8.19 ± 0.50 fL P < 0.001). Receiver operator characteristic (ROC) curve analysis suggested that the optimum cut-off point for MPV value in advanced fibrosis was 8.75 fL. (Sensitivity: 80.8%, specificity: 81.8%, positive predictive value [PPV] 77.8%, negative predictive value [NPV] 84.4%, accuracy 81.3%, AUC: 0.98 P < 0.001) CONCLUSION The current study showed that MPV is increased in CHC with advanced fibrosis. Calculation of MPV along with the use of other markers may give further information about liver fibrosis severity in CHC.

Pleiotropic cellular, hemostatic, and biological actions of Ankaferd hemostat

Sustaining hemostasis in clinical hemorrhages is a challenging task and requires extensive effort to stabilize medically hard-to-treat traumatic injuries. Several hemostatic agents are preferred to control external and internal bleedings, yet commercially available products are not sufficiently effective or fast-acting to achieve hemostasis in extreme cases. Ankaferd Blood Stopper (ABS) is a herbal extract traditionally used as a hemostatic agent. Recent studies have shown that ABS could be utilized successfully as a hemostatic agent for the management of clinical hemorrhages when conventional methods were ineffective. This review serves as a basis to provide recent findings on several applications of ABS, specifically preclinical, biological, and clinical studies both in vitro and in vivo. Another section focuses on the ultrastructural morphology and protein network formation of ABS in an effort to understand the hemostatic mechanisms of this unique agent at tissue level.

Over-expression of angiotensin-converting enzyme (CD 143) on leukemic blasts as a clue for the activated local bone marrow RAS in AML

Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting hematopoiesis. Angiotensin II type 1a (AT1a) receptors are present on the CD34+ hematopoietic stem cells. Angiotensin II stimulates the proliferation of bone marrow and umbilical cord blood hematopoietic progenitors. There are preliminary data that local RAS might also be involved in leukemogenesis. ACE hyper-function may lead to the acceleration of negative hematopoietic regulator peptide, AcSDKP, metabolism, which in turn lowers its level in the bone marrow micro-environment, finally removing the anti-proliferative effect of AcSDKP on the hematopoietic cells and blasts. Renin expression could have a role on the leukemia development and angiotensin may act as an autocrine growth factor for acute myeloid leukemia (AML) cells. The aim of this study is to search ACE (CD 143) surface antigen by flow-cytometric analyses on the leukemic blast cells taken from the bone marrow of the patients with AML. Bone marrow aspiration materials and peripheral blood samples were obtained from 11 patients with AML (eight males, three females; aged 46 (range 26–67) years) and six patients with non-malignant hematological disorders (four males, two females; aged 56 (range 22–71) years). ACE (CD 143) surface antigen was shown to be over-expressed in leukemic myeloid blast cells. ACE is positively correlated with bone marrow blast count. Elucidation of the pathological activity of the local RAS-mediated regulation of the leukemogenesis is both pathobiologically and clinically important, since the angiotensin peptides represent a molecular target in the disease management.

Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

Abstract Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients. Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin. Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 ± 0.96 fL versus 7.93 ± 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 ± 0.6 fL versus 8.9 ± 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation of gluten-free diet was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001). Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.

Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis

The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.

The role of mean platelet volume in the diagnosis of hepatocellular carcinoma in patients with chronic liver disease.

BACKGROUND/AIMS Hepatocellular carcinoma (HCC) has poor long-term prognosis so we need new diagnostic techniques and markers to detect HCC in the early phases. The aim of this study was to analyze the levels of serum mean platelet volume in HCC. METHODOLOGY The clinical data of 230 subjects with normal, chronic hepatitis, cirrhosis and HCC were retrospectively analyzed at our hospital between January 2009 and December 2009. The levels of MPV were determined in patients with liver disease and compared between patient groups and with healthy persons. RESULTS Serum MPV levels were significantly increased compared to the patients with chronic hepatitis, cirrhosis, and the control group (p<0.01). The cut-off value for MPV for the detection of HCC in cirrhotic patients was calculated as ≥9.2fl using ROC analysis [Sensitivity: 68.3%, specificity: 62.1%, AUC: 0.676 (0.580-0.773), p<0.001]. Additionally, serum MPV levels show higher sensitivity for diagnosis of HCC than AFP. An AFP of more than 7.4IU/mL and an MPV of ≥9.2fl, both put together, had a specificity of 95.2%, while when used separately, they have a sensitivity of 87.5%. CONCLUSIONS MPV may be a potential or adjunctive marker of HCC in patients with chronic liver disease.

The evaluation of bone mineral density in patients with nonalcoholic fatty liver disease

Background and aimNonalcoholic fatty liver diseases (NAFLD) are a clinical spectrum of disorders, of which nonalcoholic steatohepatitis (NASH) is the most strongly associated with inflammation. Inflammation is a known risk factor for low bone mass in the body. The primary goal of the present study was to evaluate the association between bone mineral density and liver function in patients with NASH.Materials and methodsConsenting patients with a diagnosis of NAFLD were included in the study. Extent of fatty change was graded based on ultrasonographic appearance (Grade 1, mild; Grade 2, moderate; Grade 3, severe). Bone mineral density was measured using the dual-energy x-ray absorptiometry method. ALT and hs-CRP were considered as noninvasive marker of NASH. According to ALT levels, patients were divided into two subgroups.ResultsA total of 102 patients with NAFLD and 54 healthy controls participated in the study. None of the patients with NAFLD had an abnormal bone mineral density. Furthermore, there was no difference between groups with regard to serum vitamin D levels. A subgroup analysis revealed that female patients with elevated serum ALT level had significantly lower bone mineral densities and higher hsCRP levels than female patients with normal ALT levels. The difference in vitamin D levels and body mass indices between the same subgroups was statistically insignificant.ConclusionsSimple steatosis of the liver does not affect bone mineral density. However, in a subgroup of patients with NAFLD, the presence of elevated serum ALT and hs-CRP levels, which are suggestive of NASH, was associated with lower bone mineral densities. Better understanding of the biological basis and the complex interactions between NAFLD and bone mass may help guide the clinical management of bone diseases associated with inflammation of the liver.ZusammenfassungHintergrund und ZielVom klinischen Spektrum der nicht-alkoholischen Fettlebererkrankungen (NAFLD) ist die nicht-alkoholische Steaotohepatitis (NASH) am meisten mit einer Entzündung assoziiert. Entzündung ist ein bekannter Risikofaktor für Abnahme der Knochenmasse des Körpers. Das primäre Ziel unserer Studie war es, bei Patienten mit NASH den Zusammenhang zwischen der Mineraldichte des Knochens und der Leberfunktion zu evaluieren.Material und MethodenNach Zustimmung zur Teilnahme wurden Patienten mit der Diagnose einer NAFLD in die Studie aufgenommen. Das Ausmass der Verfettung der Leber basierte auf dem sonographischen Befund (Grad 1: mild, Grad 2: mäßig, Grad 3: schwer). Die Knochendichte wurde mittels der Dualen-Energie Röntgen Absorptiomerie Methode erhoben. Die ALT und das hoch-sensitivive (hs) CRP dienten als nicht-invasive Marker der NASH: je nach ALT Werten wurden die Patienten in 2 Untergruppen eingeteilt.ErgebnisseInsgesamt nahmen 102 Patienten mit NAFLD und 54 Kontrollen an der Studie teil. Keiner der Patienten mit NAFLD hatte eine abnormale Knochendichte. Es bestand auch kein Unterschied bezüglich der Vitamin D Spiegel. Die Analyse der Subgruppen ergab, dass Frauen mit erhöhter ALT signifikant niedrigere Knochendichte und höhere hsCRP Spiegel im Vergleich zu weiblichen Patienten mit normalen ALT Spiegeln aufwiesen. Es bestand in diesen Untergruppen kein signifikanter Unterschied in den Vitamin D Spiegeln und den Body Mass Indices.SchlußfolgerungenDie Steatose der Leber allein hat keine Auswirkung auf die Mineraldichte des Knochens. In einer Untergruppe der Patienten mit NAFLD wurde jedoch bei jenen mit erhöhter ALT und hsCRP (was als Hinweis auf eine NASH gilt) eine relativ verminderte Knochendichte beobachtet. Ein besseres Verständnis der biologischen Grundlagen und der komplizierten Interaktionen zwischen den NAFLD und der Knochendichte könnten im klinischen Management von mit Entzündung der Leber assoziierten Knochenerkrankungen helfen.