Preanalytic Error Rates for the Central Laboratory of a Large-scale Public Hospital in Turkey

Abstract： The pre and post analytical phase in a testing cycle contributes up to 93% of total laboratory errors. However, pre-analytical phase is primarily responsible for errors. Hence, it is of precise importance for the laboratory to study error occurrence rates during the testing cycle and implement a quality improvement plan to release an accurate result. The present study was conducted during the period Jan-Nov 2014 in the Central Clinical Lab in Osmaniye State Hospital, Turkey. During period of 11 months, 626897 samples were monitored for major preanalytical problems at the receiving counter of the Central Clinical Laboratory. Among all preanalytic laboratory errors, 35.4% of the errors were associated with clotted sample, 25.5% errors with inadequate sample, and 25.3% errors with hemolysed sample in the laboratory. Assessment considering the departments showed that emergency unit had the highest error rates （hemolysis： 52.5%, lipemic： 42.9%, damaged： 34.6%, clotted： 34.2%, inadequate： 26.8%, wrong material： 17.6%, wrong barcode： 16.7%）. There was significant difference among the departments in terms of preanalytic errors （p 〈 0.001）. Based on these observations, major preanalytic errors are of great concern and needs corrective approach via proper educational programs to related personals. If this area is ignored, that can lead to negative patient outcome. However, a better specimen quality and patient satisfaction are achieved with the high quality personal-based education regarding pre-analytical errors.

Standardization in laboratory medicine: Adoption of common reference intervals to the Croatian population

Considering the fact that the results of laboratory tests provide useful information about the state of health of patients, determination of reference value is considered an intrinsic part in the development of laboratory medi-cine. There are still huge differences in the analytical methods used as well as in the associated reference intervals which could consequently significantly affect the proper assessment of patient health. In a constant effort to increase the quality of patients' care, there are numerous international initiatives for standardiza-tion and/or harmonization of laboratory diagnostics in order to achieve maximum comparability of laboratory test results and improve patient safety. Through the standardization and harmonization processes of analytical methods the ability to create unique reference intervals is achieved. Such reference intervals could be applied globally in all laboratories using methods traceable to the same reference measuring system and analysing the biological samples from the populations with similar socio-demographic and ethnic characteristics. In this review we outlined the results of the harmonization processes in Croatia in the field of population based reference intervals for clinically relevant blood and serum constituents which are in accordance with ongoing activity for worldwide standardization and harmonization based on traceability in laboratory medicine.

Atherogenic Indices and HDL Particle Size as Laboratory Parameters to Evaluate Cardiovascular Risk in the Presence of Dyslipidemia

Dyslipidemia may influence enzymes and transfer proteins needed to the lipoprotein particle remodeling. Calculated indices and evaluation of lipoprotein particle size have widely been used to predict cardiovascular risk. The aim of this study was to evaluate HDL particle size and LDL particle size estimate based on TG/HDL-C as well as apoB/apoA-I ratio as possible marker and atherogenic indices, respectively, of cardiovascular disease risk in the presence of dyslipidemia. We evaluated 100 individuals of both gender, without treatment with lipid-lowering drugs, 27 normolipidemic and 73 dyslipidemic, such as isolated hypercholesterolemia (n = 16), isolated hypertriglyceridemia (n = 17), low HDL-C (n = 26) and mixed dyslipidemia (n = 14). The HDL particle size did not differ between groups. The TG/HDL-C ratio was higher in groups with isolated hypertriglyceridemia (4.2 ± 1.5), low HDL-C (5.2 ± 3.1) and mixed dyslipidemia (5.3 ± 1.6). The apoB/apoA-I ratio was increased in all groups of dyslipidemia (apoB/apoA-I > 0.5) when compared to normolipidemic (apoB/apoA-I = 0.5, p < 0.001). There was a positive linear correlation between the TG/HDL-C ratio and the apoB/apoA-I ratio in low HDL-C group (r = 0.507, p = 0.008, Spearman). The results suggest that the evaluations of lipoproteins particles remodeling markers and the use of calculated indices may contribute to the evaluation of cardiovascular disease risk when dyslipidemia take place.

Corrigendum to“Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review”[J.Pharm.Anal.14(2024)100919]

Original statement in the Section 2:2.Literature search Our primary screening of 180 articles yielded the relevant data for this study.2.1.Study selection A total of 180 articles spanning from 1960 to the present day,including original research,reviews,case reports and studies reporting nitrosamine impurities above the no-observed-adverse-effect levels(NOAEL)established by regulatory agencies,were initially screened.During the primary screening,we considered factors such as relevance,publication date,access to the full article text,and content.

Processing Effects on Selected Antioxidant Activities and Metabolizing Enzyme Inhibition of M. Koneigii (Curry Leaves) Extracts

Curry leaves, scientifically termed Murraya koenigii, are renowned in South Asian cuisine for their flavor enhancement and potential health benefits, including antioxidative, anti-inflammatory, and antidiabetic properties. This study aimed to evaluate the impact of thermal processing methods on curry leaves by analysing Total Phenolic Content (TPC), Total Flavonoid Content (TFC), antioxidant activity, and metabolizing enzyme inhibition. Fresh curry leaves were subjected to thermal treatments: Oven-dried at 60˚C and Air-dried at 25˚C for 2 weeks. Extracts were prepared using Ethanol and water solvents. Results indicated that Air-dried leaves exhibited significantly higher TPC (5132.65 mg GAE/100 g) and TFC (243.13 mg CE/100 g) compared to Fresh and Oven-dried leaves. Antioxidant assays show that oven-dried curry leaves at 60˚C displayed higher results in NORS, FRAP, and TEAC assays compared to Fresh and Air-dried leaves. Ethanol extracts showed better extraction of bioactive compounds than aqueous extracts. Moreover, Lipase inhibition activity was notably high, indicating potential health benefits. This study provides valuable insights into the effects of processing methods on curry leaf extracts, emphasizing the importance of solvent selection for optimal extraction of bioactive compounds.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Hyperhomocysteinemia and Associated Biological Markers in a Congolese Population of Type 2 Diabetes Mellitus in Brazzaville

The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerative complications in type 2 diabetics. The aim of this work was to study hyperhomocysteinemia and other biochemical markers associated with T2D in the Congolese population. This was an analytical case-control study carried out between October 2022 and October 2023. The study population consisted of 150 subjects including 100 T2D patients and 50 control subjects. The main clinical data were collected on a pre-established form. Homocysteine determination was carried out by the sandwich ELISA method. The other biochemical markers were measured by colorimetric enzymatic methods. Hyperhomocysteinemia was present in 27.3% (41/150) of the entire study population. Type 2 diabetics had a frequency of hyperhomocysteinemia of 36% (36/100) and control 10% (5/50) (p = 0.001). The mean hyperhomocysteinemia concentration was 31.9 μmol/l with extremes ranging from 18 to 103 μmol/l. Means of biological markers between diabetics and controls showed a statistically significant difference (p = 0.01). The risk factors associated with this HHcy were: sex (OR = 3.5), age (OR = 9.4), sedentary lifestyle (OR = 3.4) and glycosylated hemoglobin (OR = 12) with a p-value <0.05 respectively. Our results suggest that hyperhomocysteinemia can be considered as a predictive biomarker in the bioclinic of Congolese type 2 diabetic patients.

Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease

Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.

Retinol-binding protein, acute phase reactants and Helicobacter pylori infection in patients with gastric adenocarcinoma

AIM： To determine the serum levels of c-reactive protein （CRP）, transferrin （TRF）, a2-macroglobulin （A2M）, ceruloplasmin （CER）, al-acid glycoprotein （AAG）, prealbumin （P-ALB） and retinol-binding protein （RBP） in gastric carcinoma patients and to explore their possible correlation with underlying Helicobacter pylori （H pylon） infection. METHODS： We measured the serum levels of CRP, TRF, A2M, CER, AAG, P-ALB, and RBP in 153 preoperative patients （93 males; mean age： 63.1±11.3 years） with non-cardia gastric adenocarcinoma and 19 healthy subjects. RESULTS： The levels of CRP, CER, RBP, and AAG in cancer patients were significantly higher than those in healthy controls （P〈0.0001）, while no difference was found regarding the TRF, P-ALB, and A2M levels. Cancer patients with H py/ori infection had significantly lower RBP values compared to non-infected ones （P〈0.0001） and also higher values of CRP and AAG （P = 0.09 andP = 0.08, respectively）. CONCLUSION： High serum levels of CRP, CER and AAG in cancer patients do not seem to be related to H pylori infection. Retinol-binding protein seems to discriminate between infected and non-infected patients with gastric carcinoma. Further studies are needed to explore if it is directly involved in the pathogenesis of the disease or is merely an epiphenomenon.

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

AIM： To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS： Fifty SD rats were divided into control group （n=20） and model group （n=30）. Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole （1 000：250：3）. Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid （HA）, type IV collagen （COW） and laminin （LN） were determined by radioimmunoassay. Liver tissue was fixed in formalin （10%） and 6-μm thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polydonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS： The diameter （2.207 ± 0.096 vs 1.528±0.054 mm, P〈0.01） and pressure （11.014±0.395 vs 8.533±0.274 mmHg, P〈0.01） of portal vein were significantly higher in model group than those in the control group. Plasma HA （129.97±16.10 vs 73.09±2.38 ng/mL, P〈0.01）, ColⅣ （210.49±4.36 vs 89.65±4.42 ng/mL, P〈0.01） and LN （105.00±7.29 vs 55.70±4.32 ng/mL, P〈0.01） were upregulated in model group. Abundant collagen deposited around the central vein of Iobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ. Immunohistochemical staining showed that ColⅣ protein level （0.130±0.007 vs 0.032±0.004, P〈0.01） and LN protein level （0.152±0.005 vs 0.029±0.005, P〈0.01） were up-regulated remarkably in model group. MMP-2 protein expression （2.306±1.089 vs 0.612±0.081, P〈0.01） and TIMP-1 protein expression （3.015±1.364 vs 0.446±0.009, P〈0.01） in freshly isolated hepatic nonparenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression （2.669±0.170 vs 1.695±0.008, P〈0.05）. CONCLUSION： Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcoholinduced portal hypertension in rats,

L-theanine: A potential multifaceted natural bioactive amide as health supplement

Natural bioactive compounds from plants are of great importance in modern therapeutics,which are used to prepare antibiotics, growth supplements or some other therapeutics. Ltheanine is such a bioactive amide amino acid presented in different plants and fungi,especially in tea. Theanine has influential effects on lifestyle associated diseases, such as diabetes, cardiovascular disorders, hypertension, stress relief, tumor suppression,menstruation and liver injury. This amino acid can maintain normal sleep and improve memory function and nullify effect of the neurotoxins. The rate of bioavailability and its medium of ingestion in the body is one of the great concerns for its additional antioxidant properties. Pharmacokinetics of the bioactive compound and its mode of action are described herewith. The biosynthesis and industrial synthesis are also reviewed to promote accelerated production of this bioactive compound in the pharmaceutical industries.

Neutrophil-lymphocyte ratio is useful for the prognosis of patients with hepatocellular carcinoma

There is increasing evidence that neutrophil-lymphocyte ratio (NLR) may play a role in predicting recurrence in patients with hepatitis B virus-related hepatocellular carcinoma (HCC) after liver transplantation. In the original study by Yan et al, it was aimed to determine whether an elevated NLR is associated with tumor recurrence. Total tumor size (&#x0003e; 9 cm) and macro-vascular invasion were found to be more significant than NLR according to the multivariate logistic regression analysis. Therefore, substantive significance should be emphasized rather than NLR because total tumor size and macro-vascular invasion are easier and more expressive than NLR in assessing HCC recurrence. NLR and platelet-lymphocyte ratio (PLR) are markers which are easy to obtain and can be used as inflammation indicators. Moreover, assessment of both NLR and PLR may add some value as a good predictor of risk for post-liver transplantation HCC recurrence. However, while the study was constructed on whole blood analysis, further details about the features and performance characteristics of the whole-blood analyzer, and preanalytical/analytical variables should also be mentioned.

Update on biomarkers of glycemic control

Attaining and maintaining good glycemic control is a cornerstone of diabetes care. The monitoring of glycemic control is currently based on the self-monitoring of blood glucose(SMBG) and laboratory testing for hemoglobin A1 c(HbA1 c),which is a surrogate biochemical marker of the average glycemia level over the previous 2-3 mo period. Although hyperglycemia is a key biochemical feature of diabetes, both the level of and exposure to high glucose, as well as glycemic variability, contribute to the pathogenesis of diabetic complications and follow different patterns in type 1 and type 2 diabetes. HbA1 c provides a valuable,standardized and evidence-based parameter that is relevant for clinical decision making, but several biological and analytical confounders limit its accuracy in reflecting true glycemia. It has become apparent in recent years that other glycated proteins such as fructosamine, glycated albumin, and the nutritional monosaccharide 1,5-anhydroglucitol, as well as integrated measures from direct glucose testing by an SMBG/continuous glucose monitoring system, may provide valuable complementary data, particularly in circumstances when HbA1 c results may be unreliable or are insufficient to assess the risk of adverse outcomes. Long-term associations of these alternative biomarkers of glycemia with the risk of complications need to be investigated in order to provide clinically relevant cut-off values and to validate their utility in diverse populations of diabetes patients.

Golgi localization and dynamics of hyaluronan binding protein 1 (HABP1/p32/C1QBP) during the cell cycle

Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.

Morphological Changes and Antioxidant Activity of <i>Stevia rebaudiana</i>under Water Stress

Stevia rebaudiana, a herbaceous perennial shrub contains steviol glycosides, as an alternative source of sugar for diabetic patients. Water being an integral part plays a vital role in the maintenance of plant life. Availability of water is one of the limiting factors determining plant distribution and survival in natural ecosystem. The objective of this study was to investigate the ability of tolerance of Stevia plants to water stress. Potted plants of Stevia were subjected to different levels of water regimes (100 ml, 200 ml, 300 ml) per day, whereas control plants were watered daily with about 400 ml water. Plant height, leaf area, electrolyte leakage and antioxidant enzyme activity (peroxidase and catalase) were assayed during the experimental period. All these parameters were severely affected under water stress condition. Stress treatment caused an increase in electrolyte leakage compared to control. Plant height decreased under severe stress condition whereas a sharp increase in antioxidant enzyme activity was observed in stressed plants as compared to untreated control plants. Our experiment emphasizes the importance of proper watering schedule for the cultivation of Stevia as an agricultural crop to meet the challenges for sugar and energy crisis.

Aqueous extract of Ocimum tenuiflorum decreases levels of blood glucose in induced hyperglycemic tilapia(Oreochromis niloticus)

Objective:To evaluate,in hyperglycemic tilapia[Oreochromis niloticus(O.niloticus)].the effect of this aqueous extract on blood glucose levels.Methods:The hyperglycemia in O.niloticus was induced by adding glucose to fish pond water.An aqueous extract of Ocimum tenuiflorum (O.tenuiflorum) was prepared by boiling fresh leaves and the doses of 0,40,80,200 and 400 mg per liter of pond water were tested.Results:The blood sugar concentration for tilapia with hyperglycemic induced was an average of 50%higher than the control group.The blood glucose levels in tilapia after the induction of hyperglycemia were higher than the control group for 90 min after the treatment.The treatment with the aqueous extract of O.tenuiflorum dropped the serum glucose level of hyperglycemic tilapia until it was similar to that of the control group and was dose dependent.Conclusions:The results indicated that O.tenuiflorum was endowed with anti-hyperglycemic activity.To our knowledge,this is the first report on the use of fish as a diabetes model to test natural extracts from plants.

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value.METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals.RESULTS: The mean value of HVPG was 16.18 &#x000b1; 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P &#x0003c; 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 &#x000b1; 2.6 years. The probability of cumulative survival was 39% for patients with HVPG &#x0003e; 10 mmHg and 65% for those with HVPG &#x02264; 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin &#x02264; 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68).CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Temporal changes in physiological and performance responses across game-specific simulated basketball activity

Purpose: The aims of this study were to:(1) provide a comprehensive physiological profile of simulated basketball activity and(2) identify temporal changes in player responses in controlled settings.Methods: State-level male basketball players(n = 10) completed 4 × 10 min simulated quarters of basketball activity using a reliable and valid courtbased test. A range of physiological(ratings of perceived exertion, blood lactate concentration([BLa~—]), blood glucose concentration([BGlu]), heart rate(HR), and hydration) and physical(performance and fatigue indicators for sprint, circuit, and jump activity) measures were collected across testing.Results: Significantly reduced [BLa~—](6.19 ± 2.30 vs. 4.57 ± 2.33 mmol/L; p = 0.016) and [BGlu](6.91 ± 1.57 vs. 5.25 ± 0.81 mmol/L;p = 0.009) were evident in the second half. A mean HR of 180.1 ± 5.7 beats/min(90.8% ± 4.0% HR max) was observed, with a significant increase in vigorous activity(77%—95% HR max)(11.31 ± 6.91 vs. 13.50 ± 6.75 min; p = 0.024) and moderate decrease in near-maximal activity(>95% HR_(max))(7.24 ± 7.45 vs. 5.01 ± 7.20 min) in the second half. Small increases in performance times accompanied by a significantly lower circuit decrement(11.67% ± 5.55% vs. 7.30% ± 2.16%; p = 0.032) were apparent in the second half.Conclusion: These data indicate basketball activity imposes higher physiological demands than previously thought and temporal changes in responses might be due to adapted pacing strategies as well as fatigue-mediated mechanisms.

Toxicity profile of ethanolic extract of Azadirachta indica stem bark in male Wistar rats

Objective:To investigate the loxic implications of ethanolic stem bark extract of Azadirachta indica(A-indica)at 50,100,200 and 300 mg/kg body weight in Wistar rats.Methods:Fifty male rats of Wistar strains were randomly grouped into five(A-F.)of ten animals each.Animals in Group A(control)were orally administered 1 mL of distilled water on daily basis for 21 days while those in Groups B-E received same volume of the extract corresponding to 50,100,200 and 300mg/kg body weight.Results:The extract did not significantly(P>0.05)alter the levels of albumin,total protein,red blood cells and factors relating to it whereas the white blood cell,platelets,serum triacylglycerol and high-density lipoprotein cholesterol decreased significantly(P<0.05).In contrast,the final body weights,absolute weights of the liver,kidney,lungs and heart as well as their organ-body weight ratios,serum globulins,total and conjugated bilirubin,serum cholesterol,low-density lipoprotein cholesterol and computed atherogenic index increased significantly.The spleen-body weight ratio,alkaline phosphatase,alanine and aspartate transaminases,sodium,potassium,calcium,feed and water intake were altered at specific doses.Conclusions:Overall,the alterations in the biochemical parameters of toxicity have consequential effects on the normal functioning of the organs of the animals.Therefore,the ethanolic extract of A.indica stem bark at the doses of 50,100,200 and 300 mg/kg body weight may not be completely safe as an oral remedy and should be taken with caution if absolutely necessary.

Is increased red cell distribution width an indicating marker of nonalcoholic steatohepatitis and fibrotic stage?

Red cell distribution width (RDW) may play an important role in predicting steatohepatitis and liver fibrosis. In the original study, it was aimed to determine whether RDW could be used for this purpose or not. There are studies indicating that higher RDW is correlated well with components of metabolic syndrome. Because nonalcoholic fatty liver disease is now recognized as the hepatic manifestation of metabolic syndrome, possible impact of the accompanying confounders on the study findings should have been detailed. There may be a patient selection bias due to use of improper cut-off values for alcohol consumption and inclusion of only subjects with normal aminotransferase levels and normal abdominal ultrasonography. Patients without hepatosteatosis on ultrasonography and with any restriction of aminotransferase levels should have been included in the control group, because isolated aminotransferase elevation is not decisive in the diagnosis of hepatosteatosis. Although iron, vitamin B12 and folic acid deficiencies were included in exclusion criteria, functional forms of these molecules like methylmalonic acid, homocysteine, ferritin levels and total iron binding capacity, which are more sensitive and specific parameters for vitamin B12 and folic acid deficiencies, were not mentioned. Consequently, RDW, an inexpensive, non-invasive, but powerful indicator overlooked on whole blood analysis, itself without other inflammatory markers may not accurately provide information about progression of nonalcoholic steatohepatitis and fibrosis.