Effect of the Mediterranean diet in combination with exercise on metabolic syndrome parameters: 1-year randomized controlled trial.

This work aimed to evaluate and compare the benefits of the energy restricted Mediterranean diet (MD) and Standard hypolipemic diet (SHD) accompanied by exercise on metabolic syndrome parameters. A 12-month, randomized, single-blinded, diet-controlled study was conducted on 124 obese participants in the University Hospital Dubrava. Participants were assigned to the MD (n = 63) or the SHD (n = 61) and received the same amount of nutritional education and guidance on physical activity. The completion rate was 67.7 %. Both diets produced significant beneficial changes in body weight and waist circumference (P < 0.001 for MD and SHD). Compared with the SHD, HDL cholesterol increased (P = 0.031) and systolic blood pressure (SBP) decreased (P = 0.020) in the MD group. Fasting plasma glucose decreased significantly in both diet groups (P < 0.001 for MD; P = 0.026 for SHD). Although both diets accompanied by physical activity yielded similar weight reduction results, adherence to the MD was associated with more prominent reduction of the MetS components, namely HDL level elevation and SBP reduction.

Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study.

AIM: Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile. METHODS: The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A-half an hour before breakfast; timing regimen B-an hour before the main meal of the day; timing regimen C-at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study. RESULTS: Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = -0.017 95% C.I. (-0.400-0.192); baseline vs. B = -0.325 95% C.I. (-0.562-0.023); baseline vs. C = -0.260 95% C.I. (-0.475-0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline. CONCLUSION: The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.

High absolute basophil count is a powerful independent predictor of inferior overall survival in patients with primary myelofibrosis.

OBJECTIVES: To investigate the clinical and prognostic significance of absolute basophil count (ABC) in patients with primary myelofibrosis (PMF). METHODS: We retrospectively investigated 58 patients with PMF treated in our institution in the period from 2006 to 2017. ABC was obtained in addition to other hematological and clinical parameters. Patients were separated into high and low ABC groups using the Receiver operating characteristic curve analysis. RESULTS: ABC was higher in PMF patients than in healthy controls (P < 0.001). Patients with high ABC had higher white blood cells (P < 0.001), higher red cell distribution width (P = 0.035), higher lactate dehydrogenase (P < 0.001), more frequently had circulatory blasts (P < 0.001), constitutional symptoms (P = 0.030) and massive splenomegaly (P = 0.014). ABC was also positively correlated with absolute monocyte count (AMC) (P < 0.001) and other components of differential blood count. There was no difference in ABC regarding driver mutations or degree of bone marrow fibrosis. Univariately, high ABC was significantly associated with inferior overall survival (hazard ratio (HR) 4.79, P < 0.001). This effect remained statistically significant (HR 4.27, P = 0.009) in a multivariate Cox regression model adjusted for age, gender, Dynamic International Prognostic Scoring System (HR 2.6, P = 0.001) and AMC (HR 8.45, P = 0.002). DISCUSSION: High ABC reflects higher disease activity and stronger proliferative potential of disease. ABC and AMC independently predict survival and therefore seem to reflect different underlying pathophysiologic processes. Hence, both have a potential for improvement of current prognostic scores. CONCLUSION: Basophils represent a part of malignant clone in PMF and are associated with unfavorable disease features and poor prognosis which is independent of currently established prognostic scoring system and monocytosis.

Increased mean platelet volume (MPV) is an independent predictor of inferior survival in patients with primary and secondary myelofibrosis.

Neoplastic megakaryopoiesis is a dominant feature of Philadelphia-chromosome-negative myeloproliferative neoplasms (Ph- MPNs), and elevated mean-platelet-volume (MPV) is a common finding in these diseases. The clinical and prognostic significances of MPV in patients with primary (PMF) and secondary myelofibrosis (SMF) have not been reported. We retrospectively analyzed 87 patients with myelofibrosis (66 with PMF, 21 with SMF) treated at our institution. MPV was recorded in addition to other hematological and clinical parameters. MPV was elevated in both PMF and SMF patients in comparison to controls, whereas there was no statistically significant difference between PMF and SMF. Elevated MPV was associated with lower platelets (P = 0.016), higher white blood cells (P = 0.015), higher percentage of circulatory blasts (P = 0.009), higher lactate dehydrogenase (P = 0.011), larger spleen size (P = 0.014) and higher Dynamic International Prognostic score category (P = 0.027), while there was no statistically significant association with driver mutations or degree of bone marrow fibrosis. Higher MPV was univariately associated with inferior overall survival in the whole cohort (HR = 3.82, P = 0.006), PMF (HR = 4.35, P = 0.007) and SMF patients (HR = 7.22, P = 0.034). These associations remained significant in multivariate analyses adjusted for DIPSS. Higher MPV is associated with more aggressive disease features and exhibits powerful independent prognostic properties in both PMF and SMF settings.

BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.

After the demonstration of its life-saving effect in severe hyperkalemia and the recovery of skeletal muscle after injury, pentadecapeptide BPC 157 has been shown to attenuate the local paralytic effect induced by succinylcholine, in addition to systemic muscle disability (and consequent muscle damage). Hyperkalemia, arrhythmias and a rise in serum enzyme values, were counteracted in rats. Assessments were made at 3 and 30min and 1, 3, 5, and 7 days after succinylcholine administration (1.0mg/kg into the right anterior tibial muscle). BPC 157 (10µg/kg, 10ng/kg) (given intraperitoneally 30min before or immediately after succinylcholine or per-orally in drinking water through 24h until succinylcholine administration) mitigated both local and systemic disturbances. BPC 157 completely eliminated hyperkalemia and arrhythmias, markedly attenuated or erradicated behavioral agitation, muscle twitches, motionless resting and completely eliminated post-succinylcholine hyperalgesia. BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and injected/non-injected anterior tibial muscles. Therefore, the depolarizing neuromuscular blocker effects of succinylcholine were successfully antagonized.

American Ginseng Extract (Panax quinquefolius L.) Is Safe in Long-Term Use in Type 2 Diabetic Patients.

Aim. The objective of the present study was to test the safety of supplementation with the American ginseng (AG) interventional material as an adjunct to conventional therapy (diet and/or medications) in type 2 diabetes, using a double-blind, randomized, placebo-controlled, parallel design. Methods. Each participant received either AG (10% ginsenosides) or placebo capsules (500 mg/meal = 3 g/day) for a period of 12 weeks. Outcomes included measures of safety including kidney function (urates and creatinine), liver function (AST and ALT), and haemostatic function (PV and INR). Results. Seventy-four participants with well-controlled type 2 diabetes (sex: 28 M and 46 F, age: 63 ± 9.5, BMI: 32 ± 5, and HbA1c: 7 ± 1.3), randomized to either intervention (n = 35) or control (n = 39) group, completed the study. There was no change in any of the measures of safety between treatments from baseline. The number or severity of adverse events did not differ between the AG intervention and placebo. Conclusion. Following 12 weeks of supplementation with AG, safety was not compromised in a high cardiovascular disease (CVD) risk population of patients with type 2 diabetes. This demonstrated that safety is noteworthy, as reviews have continuously warned of possible adverse effects of ginseng consumption.

Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Substantial pre-clinical and some clinical data are available showing that Asian ginseng (Panax ginseng C.A. Meyer) varieties or its particular ginsenosides exert a vasodilatating effect, thus may modulate vascular function. However, the clinical evidence for American ginseng (Panax quinquefolius L.) is scarce. Therefore, this study evaluates the effect of American ginseng (AG) on arterial stiffness, as measured by augmentation index (AI), and blood pressure (BP), in type 2 diabetes patients with concomitant hypertension. MATERIALS AND METHODS: Using a double-blind, placebo-controlled, parallel design, each participant was randomized to either the selected AG extract or placebo at daily dose of 3g for 12 weeks as an adjunct to their usual antihypertensive and anti-diabetic therapy (diet and/or medications). AI and BP were measured by applanation tonometry at baseline and after 12 weeks of treatment. RESULTS: A total of 64 individuals with well-controlled essential hypertension and type 2 diabetes (gender: 22 M:42 F, age:63 ± 9.3 years, BP: 145 ± 10.8/84 ± 8.0 mmHg, HbA1c: 7.0 ± 1.3%, fasting blood glucose (FBG): 8.1 ± 2.3 mmol/L) completed the study. Compared to placebo, 3g of AG significantly lowered radial AI by 5.3% (P=0.041) and systolic BP by 11.7% (P<0.001) at 12 weeks. No effect was observed with diastolic BP. CONCLUSIONS: Addition of AG extract to conventional therapy in diabetes with concomitant hypertension improved arterial stiffness and attenuated systolic BP, thus warrants further investigation on long-term endothelial parameters before recommended as an adjunct treatment.

Etiology and epidemiology of obstructive jaundice in Continental Croatia.

The etiology and epidemiology of obstructive jaundice in Continental Croatia has been studied in 174 patients. The objective of this research was also to explore the importance and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) as a non-surgical method of treatment of obstructive jaundice in the population of Continental Croatia. Obstructive jaundice is the illness of elderly population which is also confirmed by the information on the average age of our patients. The frequency of illness is higher among female population, and the most frequent cause of obstructive jaundice are gallstones (54.1% of patients). In 29.8% of patients the primary or secondary malignant disease was the cause of blockage in gall flow and subsequent jaundice, and the most frequent malignant cause of obstructive jaundice is pancreas cancer in 11.5% of patients. The mean value of serum concentrations of total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and gamma glutamiltransferase 24 hours before the biliary decompression by ERCP has been significantly above the upper referential value, and 24 hours after the ERCP it has dropped to normal with their statistically significant difference (p < 0.0001). The normal values of markers for synthetic liver function (total proteins and prothrombin time) have been noticed as well as elevated values of inflammatory markers in obstructive jaundice independently of etiology. Out of the total number of patients, 37.7% required the surgical treatment while 60.3% of patients were treated by ERCP, i.e. either the stone extraction or the implantation of endobiliary stent was performed.

Red blood cell distribution width as a prognostic marker of mortality in patients on chronic dialysis: a single center, prospective longitudinal study.

AIM: To determine if red cell distribution width (RDW) is associated with all-cause mortality in patients on chronic dialysis and to evaluate its prognostic value among validated prognostic biomarkers. METHODS: This is a single center, prospective longitudinal study. At the time of inclusion in January 2011, all patients were physically examined and a routine blood analysis was performed. A sera sample was preserved for determination of NT-pro-brain natriuretic peptide (NT-pro-BNP) and eosinophil cationic protein. Carotid intima media thickness (IMT) was also measured. Following one year, all-cause mortality was evaluated. RESULTS: Of 100 patients, 25 patients died during the follow-up period of one-year. Patients who died had significantly higher median [range] RDW levels (16.7% [14.3-19.5] vs 15.5% [13.2-19.7], P<0.001. They had significantly higher Eastern Cooperative Oncology Group (ECOG) performance status (4 [2-4] vs 2 [1-4], Plt;0.001), increased intima-media thickness (IMT) (0.71 [0.47-1.25] vs 0.63 [0.31-1.55], P=0.011), increased NT-pro-BNP levels (8300 [1108-35000] vs 4837 [413-35000], P=0.043), and increased C-reactive protein (CRP) levels (11.6 [1.3-154.2] vs 4.9 [0.4-92.9], Plt;0.001). For each 1% point increase in RDW level as a continuous variable, one-year all cause mortality risk was increased by 54% in univariate Cox proportional hazard analysis. In the final model, when RDW was entered as a categorical variable, mortality risk was significantly increased (hazard ratio, 5.15, 95% confidence interval, 2.33 to 11.36) and patients with RDW levels above 15.75% had significantly shorter survival time (Log rank Plt;0.001) than others. CONCLUSIONS: RDW could be an additive predictor for all-cause mortality in patients on chronic dialysis. Furthermore, RDW combined with sound clinical judgment improves identification of patients who are at increased risk compared to RDW alone.

Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157.

We demonstrate the full counteracting ability of stable gastric pentadecapeptide BPC 157 against KCl-overdose (intraperitoneal (i), intragastric (ii), in vitro (iii)), NO-system related. (i) We demonstrated potential (/kg) of: BPC 157 (10ng, 10µg ip, complete counteraction), l-arginine (100mg ip, attenuation) vs. L-NAME (5mg ip, deadly aggravation), given alone and/or combined, before or after intraperitoneal KCl-solution application (9mEq/kg). Therapy was confronted with promptly unrelenting hyperkalemia (>12mmol/L), arrhythmias (and muscular weakness, hypertension, low pressure in lower esophageal and pyloric sphincter) with an ultimate and a regularly inevitable lethal outcome within 30min. Previously, we established BPC 157-NO-system interaction; now, a huge life-saving potential. Given 30min before KCl, all BPC 157 regimens regained sinus rhythm, had less prolongation of QRS, and had no asystolic pause. BPC 157 therapy, given 10min after KCl-application, starts the rescue within 5-10min, completely restoring normal sinus rhythm at 1h. Likewise, other hyperkalemia-disturbances (muscular weakness, hypertension, low sphincteric pressure) were also counteracted. Accordingly with NO-system relation, deadly aggravation by L-NAME: l-arginine brings the values to the control levels while BPC 157 always completely nullified lesions, markedly below those of controls. Combined with l-arginine, BPC 157 exhibited no additive effect. (ii) Intragastric KCl-solution application (27mEq/kg) - (hyperkalemia 7mmol/L): severe stomach mucosal lesions, sphincter failure and peaked T waves were fully counteracted by intragastric BPC 157 (10ng, 10µg) application, given 30min before or 10min after KCl. (iii). In HEK293 cells, hyperkalemic conditions (18.6mM potassium concentrations), BPC 157 directly affects potassium conductance, counteracting the effect on membrane potential and depolarizations caused by hyperkalemic conditions.

Differential hepatoprotective mechanisms of rutin and quercetin in CCl(4)-intoxicated BALB/cN mice.

AIM: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl(4)-induced liver damage in mice. METHODS: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl(4) in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. RESULTS: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl(4)-intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl(4)-intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl(4)-induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-ß1 (TGF-ß1) than rutin. CONCLUSION: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and anti-inflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

Correlation of endothelin-1 concentration and angiotensin-converting enzyme activity with the staging of liver fibrosis.

Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30). SACE activity and ET-1 concentration were determined using commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to the severity of disease, the highest being in patients with liver cirrhosis. Maximal increase in SACE activity was found between minimal and medium fibrosis while maximal increase in ET-1 concentration was revealed between medium fibrosis and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve for SACE activity suggested a cut-off value to separate minimal from medium fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4 pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE activity and ET-1 concentration was registered (Spearman's ñ = 0.438, p = 0.004). Both SACE activity and ET-1 concentration were increased in all stages of liver fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a biochemical marker for the progression of fibrosis. Positive correlation between SACE activity and ET-1 concentration might indicate their interaction in the development of liver cirrhosis.

Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice.

Olives and olive products, an inevitable part of the Mediterranean diet, possess various beneficial effects, such as a decreased risk of cardiovascular disease and cancer. Oleuropein is a non-toxic secoiridoid found in the leaves and fruits of olive (Olea europaea L.). In this study, we have investigated the hepatoprotective activity of oleuropein in carbon tetrachloride (CCl(4))-induced liver injury in male BALB/cN mice. Oleuropein in doses of 100 and 200mg/kg was administered intraperitoneally (ip) once daily for 3 consecutive days, prior to CCl(4) administration (the preventive treatment), or once daily for 2 consecutive days 6h after CCl(4) intoxication (the curative treatment). CCl(4) intoxication resulted in a massive hepatic necrosis and increased plasma transaminases. Liver injury was associated with oxidative/nitrosative stress evidenced by increased nitrotyrosine formation as well as a significant decrease in superoxide dismutase activity and glutathione levels. CCl(4) administration triggered inflammatory response in mice livers by inducing expression of nuclear factor-kappaB, which coincided with the induction of tumor necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. In both treatment protocols, oleuropein significantly attenuated oxidative/nitrosative stress and inflammatory response and improved histological and plasma markers of liver damage. Additionally, in the curative regimen, oleuropein prevented tumor necrosis factor-beta1-mediated activation of hepatic stellate cells, as well as the activation of caspase-3. The hepatoprotective activity of oleuropein was, at least in part, achieved through the NF-E2-related factor 2-mediated induction of heme oxygenase-1. The present study demonstrates antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic activity of oleuropein, with more pronounced therapeutic than prophylactic effects.

Atrial fibrillation, atrioventricular blocks and bundle branch blocks in hemodialysis patients.

Atrial fibrillation is one of the most frequent arrhythmias diagnosed in clinical practice and it is also relatively common in dialysis patients. Atrioventricular and intraventricular conduction disturbances are less investigated in hemodialysis patients and data about their prevalence are insufficient. The objective of this study was to determine the prevalence of atrial fibrillation, atrioventricular blocks and bundle branch blocks in hemodialysis patients and to analyze different clinical risk factors. The study included 140 patients on long-term hemodialysis treatment. The presence of atrial fibrillation, atrioventricular blocks and bundle branch blocks was determined by electrocardiogram. Patients were divided into groups depending on the presence or absence of atrial fibrillation/bundle branch blocks and investigated variables were compared. Atrial fibrillation was present in 11 (7.9%) of the 140 patients. In multivariate analysis, age and higher concentration of uric acid were associated with atrial fibrillation. Prevalence of first-degree atrioventricular block was 2.9% (4 patients) and second- and third-degree atrioventricular blocks were not found. Prevalence of bundle branch blocks was 17.1% (24 patients): 5% of patients had a complete right bundle branch block, 6.4% had an incomplete right bundle branch block, 3.6% had a complete left bundle branch block and 2.1% of patients had an incomplete left bundle branch block. The prevalence of atrial fibrillation and bundle branch blocks in this study was relatively high in patients on hemodialysis and greater than that observed in general population. Presence of atrial fibrillation was associated with older age and higher concentration of uric acid.

The antioxidative protecting role of the Mediterranean diet.

Recent meta-analysis shows that adherence to a Mediterranean diet (MD) can significantly decrease the risk of overall mortality, mortality from cardiovascular diseases, as well as incidence of mortality from cancer, and incidence of Parkinson's and Alzheimer's disease. All of these diseases could be linked to oxidative stress (OS) as antioxidative effect of MD is getting more attention nowadays. Although a lot of research has been done in this area and it suggests antioxidative protective role of MD, the presented evidence is still inconclusive. The aim of this paper is to review studies investigating the effect of MD on OS, as well as to identify the areas for further research.

Effect of American ginseng (Panax quinquefolius L.) on glycemic control in type 2 diabetes.

Since diabetes tends to progressively worsen over time, glycemic control often deteriorates in spite of taking regular therapy. Therefore, numerous research studies are by and large focused on finding more efficient therapy, both new medicines for treating type 2 diabetes mellitus, as well as supplements that could serve as an addition to conventional treatment modalities. A variety of herbal preparations have been shown to have modest short-term beneficial effects on glycemia, but of these, the best studied is American ginseng (AG). AG has been shown to be effective in improving glycemic control in type 2 diabetes through increasing post-prandial insulin levels and decreasing postprandial glycemic response. However, high variability in ginsenosides may result in just as high variability in antidiabetic efficacy of over-the-counter ginseng products. Therefore, the availability of standardized extracts of AG could assist greatly in advancing our knowledge on the role of this traditionally used herb and result in a wider application of ginseng product in diabetes management. The aim of this review is to outline the efficacy and safety of American ginseng for AG preparations on glycemic control in patients with type 2 diabetes as well as to increase awareness of the evidence supporting the use of these therapies in diabetes care.

Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats.

Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) evidenced a series of pathologies, not previously reported in ibuprofen-dosed rats, namely hepatic encephalopathy, gastric lesions, hepatomegaly, increased AST and ALT serum values with prolonged sedation/unconsciousness, and weight loss. In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but was also present although to a lesser extent in the hippocampus, dentate nucleus and Purkinje cells. An anti-ulcer peptide shown to have no toxicity, the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, 10 µg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 µg, 0.16 ng/ml). Counteracted were all adverse effects, such as hepatic encephalopathy, the gastric lesions, hepatomegaly, increased liver serum values. In addition, BPC 157 treated rats showed no behavioral disturbances and maintained normal weight gain. Thus, apart from efficacy in inflammatory bowel disease and various wound treatments, BPC 157 was also effective when given after ibuprofen.

Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.

AIMS: We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype). MAIN METHODS: Herein, we used the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), an anti-ulcer peptide shown to be efficient in inflammatory bowel disease clinical trials (PL 14736) and various wound treatments with no toxicity reported. This peptide was given to antagonize combined gastrointestinal, liver, and brain toxicity induced by diclofenac (12.5mg/kg intraperitoneally, once daily for 3 days) in rats. KEY FINDINGS: Already considered a drug that can reverse the toxic side effects of NSAIDs, BPC 157 (10 µg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 µg/mL, 0.16 ng/mL). Without BPC 157 treatment, at 3h following the last diclofenac challenge, we encountered a complex deleterious circuit of diclofenac toxicity characterized by severe gastric, intestinal and liver lesions, increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally hepatic encephalopathy (brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly in the hippocampal neurons). SIGNIFICANCE: The very extensive antagonization of diclofenac toxicity achieved with BPC 157 (µg-/ng-regimen, intraperitoneally, per-orally) may encourage its further use as a therapy to counteract diclofenac- and other NSAID-induced toxicity.

Anti-cyclic citrullinated peptide and rheumatoid factor in HIV positive patients.

The aim of this study was to determine the difference of anti-CCP and RF between HIV positive patients and a healthy control group. The rheumatological complications in HIV positive patients are rather common and are recognized as a serious problem that requires more attention. Anti-CCP and RF are the only laboratory tools for rheumatoid disorder diagnostics and predictors of the course of the disease. We determined anti-CCP and RF in sera of 35 healthy volunteers and 45 HIV positive patients. Data were compared using chi-square test, Mann-Whitney test and ROC curve statistics. Both parameters were significantly higher in HIV positive patients, and significant differences between areas under the anti-CCP and RF curves were observed. Median value for anti-CCP in HIV positive patients was higher than the reference interval, and RF values were, in the reference interval, suggested by the manufacturer. Both anti-CCP and RF are significantly higher in HIV positive patients. ROC analysis showed that anti-CCP distinguishes the two groups better than RF. Because of that, it would be of a great interest to investigate the HIV positive patients after the detailed rheumatological examination.

Oxidative stress markers in patients with post-traumatic stress disorder.

Recent study data support the role of oxidative stress in diverse psychiatric disorders. Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. There are numerous studies that indicate that free radicals (FRs) damage neurons, and then play an important role in the pathophysiology of schizophrenia and depression. Active oxygen can cause considerable damage and disrupt the important physiological functions of proteins, lipids, enzymes and DNA. The aim of our study was to investigate the possible differences in the concentration of tromboxane B2, 8-OHdG and protein carbonyls, as significant markers of oxidative damage, and urate, albumin and total protein concentrations as antioxidative molecules in PTSD patients in comparison to the healthy control group. The study included 74 male participants who were active soldiers in the Croatian armed forces from 1991 to 1995. 46 subjects with chronic and current PTSD were recruited from the Department of Psychiatry of Dubrava University Hospital during 2010, 28 healthy subjects were recruited in the same period during the regular medical examination at the Dubrava University Hospital. Study results have shown that there is no statistically significant difference in urinary concentrations of 8-OHdG, serum thromboxane B2, and serum urates between two studied groups. Statistically significant difference of the protein carbonyl concentrations was examined. Concentrations were significantly lower in the PTSD group than in the control group. The clinical significance of these results was examined using ROC analysis. The obtained ROC curves did not separate the groups in a satisfactory manner.