Berberine Effects in Pre-Fibrotic Stages of Non-Alcoholic Fatty Liver Disease-Clinical and Pre-Clinical Overview and Systematic Review of the Literature.

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.

Aptamer-Based Targeting of Cancer: A Powerful Tool for Diagnostic and Therapeutic Aims.

Cancer is known as one of the most significant causes of death worldwide, and, in spite of novel therapeutic methods, continues to cause a considerable number of deaths. Targeted molecular diagnosis and therapy using aptamers with high affinity have become popular techniques for pathological angiogenesis and cancer therapy scientists. In this paper, several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently), and biosensors, which have been successfully designed for biomarkers, were critically reviewed. The results demonstrated that aptamers can potentially be incorporated with targeted delivery systems and biosensors for the detection of biomarkers expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, representing the main field of medical sciences, possess high potential for use in cancer therapy, pathological angiogenesis, and improvement of community health. The clinical use of aptamers is limited due to target impurities, inaccuracy in the systematic evolution of ligands via exponential enrichment (SELEX)stage process, and in vitro synthesis, making them unreliable and leading to lower selectivity for in vivo targets. Moreover, size, behavior, probable toxicity, low distribution, and the unpredictable behavior of nanomaterials in in vivo media make their usage in clinical assays critical. This review is helpful for the implementation of aptamer-based therapies which are effective and applicable for clinical use and the design of future studies.

Ferritin and Ferritin-to-Hemoglobin Ratio as Promising Prognostic Biomarkers of Severity in Acute Pancreatitis-A Cohort Study.

BACKGROUND: Acute pancreatitis is an inflammation of the pancreas with variable outcomes depending on its severity. Multiple systems of prediction have been proposed, each with variable specificity and sensitivity and with uneven clinical use. Ferritin is a versatile protein associated with various acute and chronic conditions. AIMS: In our study, we aimed to assess the association of serum ferritin and the ferritin-to-hemoglobin ratio (FHR) with the severity of acute pancreatitis. METHODS: A retrospective study was conducted in our hospital from January 2020 to September 2022 and included 116 patients with acute pancreatitis (graded according to the revised Atlanta classification). Serum ferritin and FHR were determined next to established laboratory parameters in the first 24 h following admission (hematological parameters, amylase, lipase, C-reactive protein, D-dimers, lactate dehydrogenase). We performed a receiver operating characteristic curve analysis for potential predictors. Also, we made correlations and conducted univariate and multivariate analyses for all potential severity biomarkers. RESULTS: The median values of serum ferritin and FHR differed significantly between patients with severe acute pancreatitis and mild cases (serum ferritin: 352.40 vs. 197.35 ng/mL, p = 0.011; FHR: 23.73 vs. 13.74, p = 0.002) and between patients with organ failure and those without organ failure (serum ferritin: 613.45 vs. 279.65 ng/mL, p = 0.000; FHR: 48.12 vs. 18.64, p = 0.000). The medians of the serum ferritin and FHR levels were significantly higher in non-survivors compared with survivors (serum ferritin: 717.71 vs. 305.67 ng/mL, p = 0.013; FHR: 52.73 vs. 19.58, p = 0.016). Serum ferritin and FHR were good predictors for organ failure and mortality, next to D-dimers and procalcitonin (AUC > 0.753 for organ failure and AUC > 0.794 for mortality). In univariate regression analysis, serum ferritin and FHR were independent variables for moderate-severe forms of acute pancreatitis. Still, adjusting the multivariate analysis, only FHR remained a significant predictor. The cut-offs for serum ferritin and FHR for predicting organ failure were 437.81 ng/mL (sensitivity, 71%; specificity, 75%) and 45.63 (sensitivity, 61%; specificity, 88%), and those for mortality during hospitalization were 516 ng/mL (sensitivity, 83%; specificity, 74%) and 51.58 (sensitivity, 66%; specificity, 86%). CONCLUSIONS: Serum ferritin and the ferritin-to-hemoglobin ratio stood out in this study as valuable and accessible predictors of disease severity in the early assessment of acute pancreatitis, next to established severity serum markers (CRP, fibrinogen, D-dimers).

Golgi Apparatus Target Proteins in Gastroenterological Cancers: A Comprehensive Review of GOLPH3 and GOLGA Proteins.

The Golgi apparatus plays a central role in protein sorting, modification and trafficking within cells; its dysregulation has been implicated in various cancers including those affecting the GI tract. This review highlights two Golgi target proteins, namely GOLPH3 and GOLGA proteins, from this apparatus as they relate to gastroenterological cancers. GOLPH3-a highly conserved protein of the trans-Golgi network-has become a key player in cancer biology. Abnormal expression of GOLPH3 has been detected in various gastrointestinal cancers including gastric, colorectal and pancreatic cancers. GOLPH3 promotes tumor cell proliferation, survival, migration and invasion via various mechanisms including activating the PI3K/Akt/mTOR signaling pathway as well as altering Golgi morphology and vesicular trafficking. GOLGA family proteins such as GOLGA1 (golgin-97) and GOLGA7 (golgin-84) have also been implicated in gastroenterological cancers. GOLGA1 plays an essential role in protein trafficking within the Golgi apparatus and has been associated with poor patient survival rates and increased invasiveness; GOLGA7 maintains Golgi structure while having been shown to affect protein glycosylation processes. GOLPH3 and GOLGA proteins play a pivotal role in gastroenterological cancer, helping researchers unlock molecular mechanisms and identify therapeutic targets. Their dysregulation affects various cellular processes including signal transduction, vesicular trafficking and protein glycosylation, all contributing to tumor aggressiveness and progression.

Concentration of heavy metals and rare earth elements in patients with brain tumours: Analysis in tumour tissue, non-tumour tissue, and blood.

Inorganic elements have been associated with brain tumours for long. The blood concentration of 47 elements was assessed by ICP-MS in 26 brain tumour patients and 21 healthy subjects from Bucharest (Romania). All 47 elements were detected in the brain tumour tissue, and 22 were detected in > 80% of samples; this implies that these elements can cross the blood-brain barrier. Median blood levels of cadmium, lead, and nickel were higher than the reference values (1.14, 53.3, and 2.53 ng/mL). Gadolinium and tantalum showed significantly higher concentrations among cases. We observed considerable differences and different profiles of the presence of inorganic elements between the tumour and non-tumour brain tissue and between tissue from the primary tumour and tissue from brain metastasis. Our data suggest that similar to heavy metals, other elements - commonly used in high tech devices and rare earth elements - can also influence brain tumour.

Serum concentration of toxic metals and rare earth elements in children and adolescent.

Biomonitoring studies are important for quantifying the body burden of pollutants and their possible effects on health. Serum concentration of 42 elements was assessed by ICP-MS in 89 children (7.2 ± 3.4 years old) from Bucharest (Romania). Levels of pollutants were compared with the clinical data obtained from routine blood tests. Clinical parameters were in the physiological range. Deficiencies of manganese, selenium, and zinc were discovered. Blood levels of elements were low. The highest levels were observed among children younger than six years. The sum of iron, selenium, barium, nickel, antimony, and cerium was positively associated with hemoglobin (Spearman rho = 0.217, P-value = 0.041), while the sum of copper, thallium, niobium, and tantalum was negatively associated (Spearman rho = -0.228, P-value = 0.032). Given the inherent sensitivity of the child population, additional studies are needed to assess the effects of these elements on their health.

Trends of Lipophilic, Antioxidant and Hematological Parameters Associated with Conventional and Electronic Smoking Habits in Middle-Age Romanians.

It is known that cigarette smoking is correlated with medical associated inquires. New electronic cigarettes are intensively advertised as an alternative to conventional smoking, but only a few studies demonstrate their harmful potential. A cross-sectional study was designed using 150 subjects from Brasov (Romania), divided into three groups: non-smokers (NS = 58), conventional cigarettes smokers (CS = 58) and electronic cigarettes users (ECS = 34). The aim of this study was to determine levels of some plasma lipophilic and hematological components, and the total antioxidant status that could be associated with the smoking status of the subjects. Serum low density lipoproteins (LDL) cholesterol increased significantly for ECS participants versus NS group (18.9% difference) (p < 0.05). Also, the CS group is characterized by an increase of serum LDL cholesterol (7.9% difference vs. NS), but with no significant statistical difference. The variation of median values of serum very low density lipoproteins (VLDL) was in order NS < ECS < CS, with statistical difference between NS and CS groups (34.6% difference; p = 0.023). When comparing the antioxidant status of the three groups, significant differences (p < 0.05) were obtained between NS vs. CS and NS vs. ECS. Similar behavior was identified for CS and ECS. Statistically significant changes (p < 0.0001) for both vitamin A and vitamin E were identified in the blood of NS vs. CS and NS vs. ECS, and also when comparing vitamin A in the blood of the CS group versus the ECS group (p < 0.05). When all groups were compared, the difference in the white blood cell (WBC) was (p = 0.008). A slight increase in the red blood cell (RBC) count was observed, but with no statistical difference between groups. These results indicated that conventional cigarette and e-cigarette usage promotes the production of excess reactive oxygen species, involving different pathways, different antioxidants and bioactive molecules.

Body burden of toxic metals and rare earth elements in non-smokers, cigarette smokers and electronic cigarette users.

Smoking is considered an important source for inorganic elements, most of them toxic for human health. During the last years, there has been a significant increase in the use of e-cigarettes, although the role of them as source of inorganic elements has not been well established. A cross-sectional study including a total of 150 subjects from Brasov (Romania), divided into three groups (non-smokers, cigarette smokers and electronic cigarettes smokers) were recruited to disclose the role of smoking on the human exposure to inorganic elements. Concentration of 42 elements, including trace elements, elements in the ATSDR's priority pollutant list and rare earth elements (REE) were measured by ICP-MS in the blood serum of participants. Cigarette smokers showed the highest levels of copper, molybdenum, zinc, antimony, and strontium. Electronic cigarette (e-cigarette) users presented the highest concentrations of selenium, silver, and vanadium. Beryllium, europium and lanthanides were detected more frequently among e-cigarette users (20.6%, 23.5%, and 14.7%) than in cigarette smokers (1.7%, 19.0%, and 12.1%, respectively); and the number of detected REE was also higher among e-cigarette users (11.8% of them showed more than 10 different elements). Serum levels of cerium and erbium increased as the duration of the use of e-cigarettes was longer. We have found that smoking is mainly a source of heavy metals while the use of e-cigarettes is a potential source of REE. However, these elements were detected at low concentrations.

Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis.

Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis.

Functional Micrococcus lysodeikticus layers deposited by laser technique for the optical sensing of lysozyme.

Whole cell optical biosensors, made by immobilizing whole algal, bacterial or mammalian cells on various supports have found applications in several fields, from ecology and ecotoxicity testing to biopharmaceutical production or medical diagnostics. We hereby report the deposition of functional bacterial layers of Micrococcus lysodeikticus (ML) via Matrix-Assisted Pulsed Laser Evaporation (MAPLE) on poly(diallyldimethylamonium) (PDDA)-coated-glass slides and their application as an optical biosensor for the detection of lysozyme in serum. Lysozyme is an enzyme upregulated in inflammatory diseases and ML is an enzymatic substrate for this enzyme. The MAPLE-deposited bacterial interfaces were characterised by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Fourier-Transformed Infrared Spectroscopy (FTIR), Raman and optical microscopy and were compared with control interfaces deposited via layer-by-layer on the same substrate. After MAPLE deposition and coating with graphene oxide (GO), ML-modified interfaces retained their functionality and sensitivity to lysozyme's lytic action. The optical biosensor detected lysozyme in undiluted serum in the clinically relevant range up to 10µgmL-1, in a fast and simple manner.

Phytomedicine in Joint Disorders.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even though many of them have been proven effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarize the available scientific information on the following joint-friendly medicinal plants, which have been tested in human studies: Arnica montana, Boswellia spp., Curcuma spp., Equisetum arvense, Harpagophytum procumbens, Salix spp., Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Whitania somnifera.

Estimating the yin-yang nature of Western herbs: a potential tool based on antioxidation-oxidation theory.

BACKGROUND: One of the biggest obstacles to progress in traditional Chinese medicine (TCM) development in Western countries is the difficulty of applying the traditional concepts to the Western medicinal plants, which are not traditionally described in ancient literature. During recent years, new advances in the field of understanding Yin/Yang aspects from a modern bioscientific point of view have led to the conclusion that antioxidationoxidation concepts might mirror a Yin-Yang relationship. METHODS: This study was intended to integrate the Yin-Yang theory of the traditional Chinese medicine with modern antioxidation-oxidation theory, and to propose a biochemical tool based on redox parameters (e.g. antioxidant capacity, chemiluminescence-CL signal inducing capacity), usable for the classification of Western medicinal plants from Yin/Yang perspective. Trolox equivalent antioxidant capacity (TEAC) of six vegetal aqueous extracts (Symphitum officinalae (radix)-SYM, Inula helenium (radix)-INU, Calendula officinalis (flores)-CAL, Angelica arhanghelica (folium)ANG(F), Angelica arhanghelica (radix)-ANG(R), Ecbalium Elaterium (fruits)-ECB) and luminol-enhanced chemiluminescence of PMNL on addition of these vegetal extracts were measured. Percentages from the maximal or minimal values obtained were calculated for each extract (TEAC%, PMNL stimulation%, PMNL inhibition%, relative speed of action% (RSA%%)), specific Yin-Yang significance was assigned to each relative parameter. In the end, an integration of all the relative values was done, in order to find a global "Yin" or a "Yang" trait of each vegetal extract. RESULTS: TEAC decreased in the following order: SYM > INU > CAL >ANG(F) > ANG(R > ECB. Three vegetal extracts (SYM > INU > ECB) decreased the luminol-enhanced chemiluminescence of PMNL, two (ANG(R) > ANG(F)) increased it, while one (CAL) had a dual effect. After the integration of the percentages, CAL was found to have a global "Yang" trait, while the rest of the plants had a global "Yin" trait. CONCLUSIONS: TEAC% and PMNL inhibition% appears to correlate with the Yin properties of herbs, while PMNL stimulation% and RSA% might correlate with Yang aspects within the formal TCM classification system, and may be useful criteria in describing the Western herbs from a TCM point of view.

A study of antioxidant activity in patients with schizophrenia taking atypical antipsychotics.

INTRODUCTION: Atypical antipsychotics have significantly improved the quality of life for schizophrenic patients. Despite their beneficial effects, these antipsychotics induce weight gain, diabetes, and dyslipidemia. The aims of this study were to investigate the antioxidative activity of paraoxonase and assess lipid profile as a cardiovascular risk factor in patients with schizophrenia under long-term clozapine or risperidone treatment. METHODS: The study included 66 patients with schizophrenia under clozapine or risperidone treatment and 19 healthy control subjects. Serum paraoxonase activities against paraoxon (PON(PO)), phenylacetate (PON(PA)), dihydrocoumarin (PON(DHC)), serum Trolox equivalent antioxidant activity (TEAC), antioxidant gap (GAP), and lipid profile were determined. RESULTS: PON(DHC) activity was reduced in both antipsychotic drug-treated groups (clozapine 43.46 ± 1.06 U/ml, p < 0.001; risperidone 50.57 ± 1.54 U/ml, p < 0.01; control 52.27 ± 1.34 U/ml). A similar pattern was observed for the PON(DHC)/HDL-cholesterol (HDLC) ratio. On the contrary, PON(PO) and PON(PA) were increased in the treated group, but the corresponding paraoxonase/HDLC ratios were not significantly different from controls, except for PON/HDLC in the clozapine group. TEAC and GAP were only decreased in the clozapine-treated group. CONCLUSIONS: In patients with schizophrenia, clozapine or risperidone treatment had different effects on various paraoxonase activities. The results of the present study suggest that patients with schizophrenia might be at increased risk for metabolic and cardiovascular disease related to reduced PON(DHC), TEAC, and GAP.

Erythrocyte membrane stability to hydrogen peroxide is decreased in Alzheimer disease.

The brain and erythrocytes have similar susceptibility toward free radicals. Therefore, erythrocyte abnormalities might indicate the progression of the oxidative damage in Alzheimer disease (AD). The aim of this study was to investigate erythrocyte membrane stability and plasma antioxidant status in AD. Fasting blood samples (from 17 patients with AD and 14 healthy controls) were obtained and erythrocyte membrane stability against hydrogen peroxide and 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH), serum Trolox equivalent antioxidant capacity (TEAC), residual antioxidant activity or gap (GAP), erythrocyte catalase activity (CAT), erythrocyte superoxide dismutase (SOD) activity, erythrocyte nonproteic thiols, and total plasma thiols were determined. A significant decrease in erythrocyte membrane stability to hydrogen peroxide was found in AD patients when compared with controls (P<0.05). On the contrary, CAT activity (P<0.0001) and total plasma thiols (P<0.05) were increased in patients with AD compared with controls. Our results indicate that the most satisfactory measurement of the oxidative stress level in the blood of patients with AD is the erythrocyte membrane stability to hydrogen peroxide. Reduced erythrocyte membrane stability may be further evaluated as a potential peripheral marker for oxidative damage in AD.

Paraoxonase lactonase activity, inflammation and antioxidant status in plasma of patients with type 1 diabetes mellitus.

OBJECTIVES: To investigate paraoxonase-1 (PON1) lactonase activity, myeloperoxidase (MPO) activity (as a marker of inflammation) and antioxidant status in plasma of patients with type 1 diabetes mellitus. METHODS: Whole blood and plasma samples were collected from patients with diabetes and healthy control subjects. PON1 lactonase and MPO activities and total antioxidant capacity (TEAC) were determined in plasma. Glycosylated haemoglobin (HbA1c) was quantified in whole blood. RESULTS: Plasma PON1 lactonase and MPO activities were significantly higher and TEAC was significantly lower in patients with diabetes (n = 18) compared with healthy control subjects (n = 20). There were significant positive correlations between PON1 lactonase activity and MPO activity and HbA1c level, and plasma MPO and HbA1c. There were significant negative correlations between PON1 lactonase activity and TEAC, and MPO activity and TEAC. CONCLUSIONS: Increased lactonase activity may inefficiently compensate for the high level of chronic inflammation and low antioxidant capacity in the plasma of patients with type 1 diabetes mellitus.

A new insight into estrogen signaling: Yin-Yang perspective.

During recent years, new advances in the field of estrogen signaling (e.g., the discovery of the second estrogen receptor named ERß) have led to the conclusion that all the major human tissues are estrogen-responsive. The impact of estrogen on human health is far more complex and stronger than scientists had previously thought. Several scientists suggested that the interplay between ERα and ERß (antagonism, synergism, etc.) simulates a Yin-Yang relationship. This article is intended to integrate the Yin-Yang theory of Traditional Chinese Medicine with modern scientific findings on estrogen signaling to offer a better understanding of the complex interactions between ERα and ERß. A different approach, such as that of Yin-Yang theory, may complete the standard scientific perspective, reveal hidden meanings of the tissue-dependent ERα-ERß predominance, and reveal new aspects of estrogen-receptor imbalance.

Chelidonium majus--an integrative review: traditional knowledge versus modern findings.

Chelidonium majus L. (family Papaveraceae), or greater celandine, is an important plant in western phytotherapy and in traditional Chinese medicine. Crude extracts of C. majus as well as purified compounds derived from it exhibit a broad spectrum of biological activities (antiinflammatory, antimicrobial, antitumoral, analgesic, hepatoprotective) that support some of the traditional uses of C. majus. However, herbal medicine also claims that this plant has several important properties which have not yet been scientifically studied: C. majus is supposed to have diuretic, antitussive and eye-regenerative effects. On the other hand, C. majus also has scientifically proven effects, e.g. anti-osteoporotic activity and radioprotection, which are not mentioned in traditional sources. Moreover, recent controversy about the hepatoprotective versus hepatotoxic effects of Chelidonium majus has renewed the interest of the medical community in this plant. This review is intended to integrate traditional ethno-medical knowledge and modern scientific findings about C. majus in order to promote understanding of its therapeutic actions as well as its toxic potential.

Protection of erythrocyte membrane against oxidative damage by geriforte in healthy human subjects.

The influence of Geriforte, an Ayurvedic natural supplement, on the antioxidant defense systems in human erythrocytes and plasma was investigated in an open human clinical study. The ability of Geriforte to inhibit the azo-bis 2-amidinopropane dihydrochloride (AAPH) dependent lysis of erythrocytes was also evaluated. Geriforte supplementation increased the activity of erythrocyte catalase (265.745 +/- 15.768 vs. 352,329 +/- 18.480 K/g Hb/mL, p < 0.01) and reduced the free radical mediated cytotoxicity induced by azo-bis 2-amidinopropane dihydrochloride (AAPH), which was measured by erythrocyte membrane stability assay (0.0439 +/- 0.0069 vs. 0.1291 +/- 0.0396 C50- AAPH (mM), p < 0.05). The intervention did not change significantly the activity of erythrocyte superoxide dismutase and the plasma levels of antioxidant agents. The results indicate that Geriforte possesses cytoprotective properties on erythrocytes against oxidative challenge and specific antioxidant activity, which involves mainly the intracellular protective systems and the membranes.

Diabetic foot patients with and without retinopathy and plasma oxidative stress.

OBJECTIVE: The first aim of this study was to evaluate some plasma oxidative stress markers in diabetic patients (type2 diabetes mellitus) with peripheral arteriopathy. Secondly, these patients were divided into two groups considering the presence or absence of retinopathy. The differences in the levels of the oxidative stress parameters could be important to select patients prone to develop multiple vascular complications, including retinopathy. PATIENTS AND METHODS: Forty hospitalized type II diabetic patients, aged between 40 and 70, with stage III or IV foot ulceration according to the Wagner classification, had an ophthalmologic evaluation for retinopathy. Among them, 23 were with retinopathy with different grades of severity and 17 were without retinopathy. Twenty healthy subjects served as a control group. Fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, total serum proteins, serum uric acid and plasma ceruloplasmin levels were determined and compared. RESULTS: Plasma levels for fasting glucose, glycosylated hemoglobin, ceruloplasmin and serum concentrations for fructosamine and uric acid were significantly increased in diabetic foot patients vs. control subjects. Comparing the two groups of patients, with and without retinopathy, the concentrations of ceruloplasmin and uric acid were significantly increased in diabetic patients with retinal disease. In diabetic patients with retinopathy, positive correlations were calculated between glycated hemoglobin and fructosamine concentrations and between glycated hemoglobin and ceruloplasmin. CONCLUSION: Diabetic foot patients with retinopathy have increased plasma levels of uric acid and ceruloplasmin. These plasma compounds could be important in the pathogenesis of retinal disease. Two aspects should be considered when these high values are analysed. First, these antioxidant compounds may become prooxidant in diabetic vascular environment. Secondly, it is not known whether these modified plasma oxidative stress parameters are cause or effect in diabetic complication development.

A comparative oxidative stress study--obesity with and without diabetes mellitus.

Oxidative stress and inflammation are involved in the initiation and progression of obesity and diabetes mellitus. The aim of our study was to find out some markers of oxidative stress in twenty obese patients with type 2 diabetes mellitus (group D) and twenty age-matched obese subjects (group O) and compare the results with the control values from twenty matched healthiy subjects (group H). Spectrophotometric methods were used. For the following plasma parameters: ceruloplasmin, d-ROM (determinable Reactive Oxygen Metabolites), alpha-dicarbonyls, the values were modified in the same way for the groups of patients versus healthy subjects. The patients had higher alpha-dicarbonyls levels than the controls (for D versus H, p<0.047 and for O versus H, p<0.043). There were not significant differences for plasma ceruloplasmin and d-ROM levels. Comparing group O versus D, all the above parameters had very close values. The antioxidant capacity (AC) was higher in group O versus group H (p<0.001) and higher in group O versus D (p<0.02). The high AC for obese patients may be due to hyperuricemia. A negative correlation between AC and d-ROM concentrations and a positive correlation between ceruloplasmin and AC levels was observed for group D. Our data underline that in type 2 diabetes mellitus and obesity, the plasma markers of oxidative stress are modified in the same way. Oxidative stress may be a "connector" between these two diseases. Probably body fat reduction (for obese individuals) diminishes oxidant formation and, in its turn, the incidence of obesity related diseases, such as diabetes mellitus.