Oxidative Stress and Inflammation Biomarkers in Postoperative Pain Modulation in Surgically Treated Patients with Laryngeal Cancer-Pilot Study.

(1) Background: Surgical treatment of laryngeal carcinoma includes different types of laryngectomies with neck dissection. Surgical tissue damage triggers an inflammatory response, leading to the release of pro-inflammatory molecules. This increases reactive oxygen species production and decreases antioxidant defense mechanisms, leading to postoperative oxidative stress. The aim of this study was to assess the correlation between oxidative stress (malondialdehyde, MDA; glutathione peroxidase, GPX; superoxide dismutase, SOD) and inflammation (interleukin 1, IL-1; interleukin-6, IL-6; C-reactive protein, CRP) parameters and postoperative pain management in patients surgically treated with laryngeal cancer. (2) Methods: This prospective study included 28 patients with surgically treated laryngeal cancer. Blood samples were taken for the analysis of oxidative stress and inflammation parameters before the operative treatment and after the operative treatment (1st postoperative day and 7th postoperative day). The concentrations of MDA, SOD, GPX, IL-1, IL-6, and CRP in the serum were determined by coated enzyme-linked immunosorbent assay (ELISA). The visual analog scale (VAS) was used for pain assessment. (3) Results and conclusion: There was a correlation between oxidative stress and inflammation biomarkers and postoperative pain modulation in surgically treated patients with laryngeal cancer. Age, more extensive surgery, CRP values, and use of tramadol were predictors for oxidative stress parameters.

Ketamine, an Old-New Drug: Uses and Abuses.

Ketamine as an old-new drug has a variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine in standard doses is principally utilized for the induction and maintenance of surgical procedures. Besides its use in anesthesia and analgesia, recent studies have shown that ketamine has found a place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Ketamine primarily functions as a noncompetitive antagonist targeting the N-methyl-D-aspartate (NMDA) receptor, but its mechanism of action is complex. It is generally regarded as safe, with low doses and short-term use typically not leading to significant adverse effects. Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drugs.

Correlation of Ionized Magnesium with the Parameters of Oxidative Stress as Potential Biomarkers in Patients with Anxiety and Depression: A Pilot Study.

Background: Magnesium (Mg) is the second most abundant intracellular cation. Ionized Mg is the only active form of Mg. The concentration of ionized Mg could be a potentially novel biomarker for anxiety and depression. Aim: The aim of this study was to assess the serum concentration of ionized Mg and its correlation with biomarkers of oxidative stress and inflammation in patients with anxiety and depression. Methods: In this study included 93 respondents were divided into 3 groups: C (control group-18 respondents); A (patients with anxiety disorder, dissociative/conversion disorders and somatoform disorders-36 patients); D (patients with depression-39 patients). Clinical diagnosis was based on ICD-10 criteria. Blood samples were used for standard laboratory analysis, ionized Mg analysis, oxidative stress, and inflammatory parameters. Results: Statistical significance was recorded between healthy volunteers and patients (anxiety/depression) in ionized Mg values. In anxious patients, malondialdehyde (MDA) had a positive correlation between the parameters of oxidative stress with ionized Mg. In depressive patients, MDA had a positive correlation, and glutathione peroxidase 1 (GPX1) a negative correlation with the concentration of ionized Mg. Conclusion: Ionized Mg and its correlation with parameters of oxidative stress could be potential biomarkers in anxious and depressive patients.

Immune Cell and Biochemical Biomarkers in Advanced Laryngeal Cancer.

Objective: The aim of this study was to evaluate cell and biochemical biomarkers and establish their prognostic value in patients with advanced laryngeal cancer. Material and Methods: A prospective study included 52 patients with advanced laryngeal carcinoma surgically treated at the tertiary referral center. Tumor tissue was immunohistochemically stained for T-cell markers (CD4 and CD8), and levels of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood samples. Results: Overall 3-year survival (OS) of patients included in the study was 69.2% and the disease specific survival (DSS) 72.5%. Higher expression of CD4+ and CD8+ were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. Levels of IL-8 were a significant predictor of 3-year OS and DSS survival in patients with advanced laryngeal cancer but not levels of IL-6 and CRP values. Conclusion: Though high expression of CD4 and CD8 were demonstrated in the tumor tissue, but their prognostic role was not established. Higher values of IL-8 proved to be significant negative predictor of DSS. This could further collaborate the inclusion of combination of biomarkers in assessment of favorable treatment choice in patients with advanced laryngeal carcinoma.

Treatment of Peripartum Depression with Antidepressants and Other Psychotropic Medications: A Synthesis of Clinical Practice Guidelines in Europe.

This study examined (1) the availability and content of national CPGs for treatment of peripartum depression, including comorbid anxiety, with antidepressants and other psychotropics across Europe and (2) antidepressant and other psychotropic utilization data as an indicator of prescribers' compliance to the guidelines. We conducted a search using Medline and the Guidelines International Network database, combined with direct e-mail contact with national Riseup-PPD COST ACTION members and researchers within psychiatry. Of the 48 European countries examined, we screened 41 records and included 14 of them for full-text evaluation. After exclusion of ineligible and duplicate records, we included 12 CPGs. Multiple CPGs recommend antidepressant initiation or continuation based on maternal disease severity, non-response to first-line non-pharmacological interventions, and after risk-benefit assessment. Advice on treatment of comorbid anxiety is largely missing or unspecific. Antidepressant dispensing data suggest general prescribers' compliance with the preferred substances of the CPG, although country-specific differences were noted. To conclude, there is an urgent need for harmonized, up-to-date CPGs for pharmacological management of peripartum depression and comorbid anxiety in Europe. The recommendations need to be informed by the latest available evidence so that healthcare providers and women can make informed, evidence-based decisions about treatment choices.

Interactions between Ketamine and Magnesium for the Treatment of Pain: Current State of the Art.

BACKGROUND: Over the past three decades, NMDA-receptor antagonists have been shown to be efficient drugs for treating pain, particularly pain resistant to conventional analgesics. Emphasis will be on the old-new drugs, ketamine and magnesium, and their combination as a novel approach for treating chronic pain. METHODS: The MEDLINE database was searched via PubMed for articles that were published up to March 1, 2020, with the keywords 'ketamine', 'magnesium', and 'pain' (in the title/abstract). RESULTS: Studies in animals, as well as humans, have shown that interactions of ketamine and magnesium can be additive, antagonistic, and synergistic. These discrepancies might be due to differences in magnesium and ketamine dosage, administration times, and the chronological order of drug administration. Different kinds of pain can also be the source of divergent results. CONCLUSION: This review explains why studies performed with a combination of ketamine and magnesium have given inconsistent results. Because of the lack of efficacy of drugs available for pain, ketamine and magnesium in combination provide a novel therapeutic approach that needs to be standardized with a suitable dosing regimen, including the chronological order of drug administration.

Lithium - Pharmacological and Toxicological Aspects: The Current State of the Art.

Lithium is the smallest monovalent cation with many different biological effects. Although lithium is present in the pharmacotherapy of psychiatric illnesses for decades, its precise mechanism of action is still not clarified. Today lithium represents first-line therapy for bipolar disorders (because it possesses both antimanic and antidepressant properties) and the adjunctive treatment for major depression (due to its antisuicidal effects). Beside, lithium showed some protective effects in neurological diseases including acute neural injury, chronic degenerative conditions, Alzheimer's disease as well as in treating leucopenia, hepatitis and some renal diseases. Recent evidence suggested that lithium also possesses some anticancer properties due to its inhibition of Glycogen Synthase Kinase 3 beta (GSK3ß) which is included in the regulation of a lot of important cellular processes such as: glycogen metabolism, inflammation, immunomodulation, apoptosis, tissue injury, regeneration etc. Although recent evidence suggested a potential utility of lithium in different conditions, its broader use in clinical practice still trails. The reason for this is a narrow therapeutic index of lithium, numerous toxic effects in various organ systems and some clinically relevant interactions with other drugs. Additionally, it is necessary to perform more preclinical as well as clinical studies in order to a precise therapeutic range of lithium, as well as its detailed mechanism of action. The aim of this review is to summarize the current knowledge concerning the pharmacological and toxicological effects of lithium.

Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats.

Gentamicin, belonging to the aminoglycosides, possesses the greatest nephrotoxic effect of all other antibiotics from this group. On the other hand, pioglitazone, which represents peroxisome proliferator-activated receptor γ (PPARγ) agonist recently showed antiinflamatory, antioxidative effects, amelioration of endothelial dysfunction etc. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. These effects were observed by following values of biochemical (serum urea and creatinine) parametars, total histological kidney score, urine level of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as well as parametars of oxidative stress (malondialdehyde, superoxide dismutase, catalase, total oxidant status, total antioxidant status, oxidative stress index and advanced oxidation protein products). It seems that pioglitazone protects the injured rat kidney in a U-shaped manner. Medium dose of pioglitazone (1 mg/kg, i.p.) was protective regarding biochemical (serum urea and creatinine), total histological score and the values of kidney injury molecule-1 (KIM-1) (P < 0.05 vs. control group, i.e. rats injected with gentamicin only). This finding could be of great importance for the wider use of aminoglycosides, with therapy that would reduce the occurrence of serious adverse effects, such as nephrotoxicity and acute renal failure.

Involvement of serotonergic and opioidergic systems in the antinociceptive effect of ketamine-magnesium sulphate combination in formalin test in rats.

BACKGROUND: Ketamine and magnesium sulphate showed synergic interaction in the tail-immersion test and additive interaction in the rat formalin test. Aim of study was to evaluate the influence of serotonergic and opioidergic system of this combination in the formalin test in rats. METHODS: Antinociceptive activity was assessed by the formalin test in male Wistar rats (200-250 g). Antagonists (naloxone and methysergide) were administrated 5 min before and magnesium sulphate 5 min after ketamine injection. Formalin (2.5%, 100 µL) was injected into the right hind paw surface (intraplantar) of rats 5 min after ketamine/magnesium combination. Data were recorded as the total time spent in pain related behavior after the injection of formalin or vehicle (0.9% NaCl). RESULTS: In the intermediate phase of the formalin test, methysergide at a dose of 0.2 mg/kg did not have any effect, but at doses of 0.5 and 1 mg/kg it had a pronociceptive effect. Methysergide (0.2, 0.5 and 1 mg/kg) inhibited the antinociceptive effect of ketamine-magnesium sulphate combination. In the intermediate phase, naloxone at a dose of 0.2 mg/kg did not have any effect, but at a dose of 3 mg/kg it produced a pronociceptive effect. Naloxone (0.2 and 3 mg/kg) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulphate (5 mg/kg) combination. CONCLUSION: The results of the present study suggest that serotonergic and opioidergic systems are involved, at least in part, in the antinociceptive effect of the ketamine-magnesium sulphate combination in the model of inflammatory pain in rats.

Pain Management After Surgical Tonsillectomy: Is There a Favorable Analgesic?

The aim of this study was to examine how ibuprofen and paracetamol prevent pain after cold-steel extracapsular tonsillectomy in children. Also, we examined the relation between age, gender, nausea, postoperative bleeding, antibiotic use, type of diet, and postoperative pain intensity and the type of administered analgesic. A prospective study was conducted on 147 children (95 males and 52 females, aged 7-17 years) who underwent tonsillectomy in the Clinical-Hospital Center "Dragisa Misovic" from January 1 to June 30, 2016. The degree of pain was measured using a visual analog scale (VAS). We did not observe any significant differences in postoperative nausea, hospitalization rate postoperative bleeding, and antibiotic use between the paracetamol and ibuprofen groups. A test of within-patient effects showed that VAS scores changed significantly during the postoperative follow-up period (P = .00), but there were no significant differences between the groups (P = .778). After 12 hours, 29.3% of the patients on paracetamol and 21.8% on ibuprofen were transferred to a soft diet; after 24 hours, 84.8% of the paracetamol group and 85.5% of the ibuprofen group were on a soft diet (χ2 test, P < .05). There was a statistically significant correlation between VAS scores measured 4 hours after the surgery and the time of transference to the soft diet (Spearman ρ test, P < .001). The transfer to soft and normal diets was not significantly different between the 2 groups as assessed by the VAS scores (Pearson χ2 test, P = .565).There is still no consensus on the most effective postoperative pain-control regiment after tonsillectomy. This study showed that satisfactory pain management was achieved equally with both paracetamol and ibuprofen.

Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity.

A toxicity evaluation of two Keggin-type heteropolytungstates, K7[Ti2PW10O40]·6H2O and K6H[SiV3W9O40]·3H2O, with different inhibitory potencies toward acetylcholinesterase activity (IC50 values of 1.04×10-6 and 4.80×10-4mol/L, respectively) was performed. Wistar albino rats were orally treated with single doses (5 and 50mg/kg) of both investigated compounds. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined after 24h and 14days. A histopathological analysis of liver tissue was carried out 14days after the polyoxotungstate administration. Both applied doses of the investigated compounds did not induce statistically significant alterations of the renal function markers. However, the polyoxotungstate treatment caused an increase in the activities of serum alanine transaminase and aspartate aminotransferase in a time- and concentration-dependent manner, although statistically significant changes in bilirubin concentrations were not observed. Furthermore, the detected hepatotoxic effect was confirmed by histhopathological analysis that suggested some reversible liver tissue damage two weeks after the treatment, especially in the case of K6H[SiV3W9O40]·3H2O. Accordingly, the toxicity of these two polyoxotungstates with anti-acetylcholinesterase effect cannot be considered as a severe one, but their potential clinical application would require a more complex toxicological study.

Additive and antagonistic antinociceptive interactions between magnesium sulfate and ketamine in the rat formalin test.

Because ketamine and magnesium block NMDA receptor activation by distinct mechanisms of action, we hypothesized that in a model of inflammatory pain in rats the combination of ketamine and magnesium might be more effective than ketamine alone. Antinociceptive activity was assessed by the formalin test in male Wistar rats (200-250 g). Animals were injected with 100 µL of 2.5% formalin to the plantar surface of the right hind paw. Data were recorded as the total time spent in pain-related behavior after the injection of formalin or vehicle (0.9% NaCl). Ketamine and magnesium sulfate given separately reduced nocifensive behavior in the second phase of the formalin test in rats. When ketamine was applied after magnesium sulfate, the log dose-response curves for the effects of ketamine and the magnesium sulfate-ketamine combination revealed antagonistic interaction, and about 1.6 (CL 1.2-2.4) fold increment in ketamine dosage. A low dose of magnesium sulfate (5 mg/kg, subcutaneously) administered after ketamine increased the antinociceptive effect of ketamine by a factor of only 1.2 (CL 0.95-1.38), indicating an additive interaction. There was a 1.8-fold reduction in dosage of ketamine when ketamine was administered before rather than after the magnesium sulfate. The present study revealed that both ketamine and magnesium reduced pain-related behavior in the second phase of the formalin test in rats. Ketamine, when administered before or after the magnesium, provided additive or antagonistic antinociceptive interactions, respectively. Whether there will be an additive or antagonistic antinociceptive interaction between ketamine and magnesium depends on the order of drug administration.

The Efficacy and Safety of Antipsychotic Medications in the Treatment of Psychosis in Patients with Parkinson's Disease.

Psychotic symptoms are present in up to 50% of patients with Parkinson's disease. These symptoms have detrimental effects on patients' and caregivers' quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson's disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson's disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson's disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson's disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug's long-term safety and efficacy.

Pharmacotherapy of Pain in the Older Population: The Place of Opioids.

Pain is a common symptom in older people. It is possible that pain is underreported in older persons due to an incorrect belief that it is an inevitable part of aging. Opioid analgesics are potent medications, with confirmed efficacy for the treatment of moderate to severe pain. These drugs are commonly used in older persons. However, there is insufficient evidence regarding safety of opioids in older patients. One of the reasons for this is the lack of randomized, controlled clinical trials. People of advanced age often have comorbidites and use other prescription drugs, as well as over-the-counter (OTC) compounds, thus making them more suceptible to the risk of interactions with opioids. Significant pharmacokinetic and pharmacodynamic changes that occur with advancing age increase the risk of adverse effects of opioids. There are also some discrepancies between guidelines, which recommend the use of lower doses of opioids in older patients, and the findings in the literature which suggest that pain is often undertreated in this age group. It seems that there are significant variations in the tolerability of different opioid analgesics in older people. Morphine, fentanyl, oxycodone, and buprenorphine are still the preferred evidence-based choices for add-on opioid therapy for these patients. However, the safety and efficacy of other opioids in older patients, especially if comorbidities and polypharmacy are present, is still questionable. This review addresses the most important aspects of the use of opioids in older persons, focusing on pharmacokinetics, pharmacodynamics, adverse effects, and interactions.

Evaluation of Novel Biomarkers of Acute Kidney Injury: The Possibilities and Limitations.

Despite the recent findings concerning pathogenesis and novel therapeutic strategies, the mortality rate in patients with acute kidney injury (AKI) remains very high. Early detection of patients with impaired renal function may help to ensure more aggresive treatment and to improve clinical outcome. Serum creatinine is still gold standard of kidney injury, although it is well known as an insensitive and unreliable biomarker (for example, its concentration does not increase significantly until about half of the kidney function is lost). Considering these data, researches and clinicians are making great efforts in the past decade in order to discover and validate novel AKI biomarkers. Kidney injury molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), Interleukin-18 (IL-18), Cystatin C (Cys-C) are some of new, promising markers of kidney damage which are currently in the focus of preclinical and clinical studies. Recent data suggest that some of these new biomarkers represent important parametars of acute tubular necrosis (ATN) and reliable predictors of development and prognosis of AKI. Beside that, monitoring of these markers could have significant importance for early diagnosis and clinical course, not only in patients with various forms of AKI and other renal diseases, but also in patients with cardiorenal syndrome, heart failure, cardiopulmonary bypass, cardiothoracical surgical interventions, in the pediatric emergency setting etc. The aim of this review is to summarize the literature data concerning some new biomarkers, evaluate their role as well as their limitations in the early diagnosis and predict clinical outcome of some renal diseases.

Prevention of Renal Complications Induced by Non- Steroidal Anti-Inflammatory Drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain, inflamation and fever. They are usually well tolerated in healthy persons, but in patients with risk factors (advanced age, renal impairment, heart failure, liver disease, concurrent medications with antihypertensive drugs), NSAIDs can induce serious renal adverse effects. They include sodium and water retention with edema, worsening of heart failure, hypertension, hyponatremia, hyperkalemia, acute kidney injury, chronic kidney disease, renal papillary necrosis and acute interstitial nephritis. The majority of these adverse effects are due to the inhibition of prostaglandins synthesis and they are dose and duration-dependent. Acute forms of kidney injuries are transient and often reversible upon drug withdrawal. Chronic use of NSAIDs in some patients may result in chronic kidney disease. It is recommended that patients at risk should have preventative strategies in place, including the use of the "lowest effective dose" of NSAID for the "shortest possible time" and monitoring renal function, fluid retention and electrolyte abnormalities. Patients who are taking antihypertensive medications should be monitored for high blood pressure and the doses of antihypertensive medications should be adjusted if needed. In general, the combination of NSAIDs and angiotensin inhibitors should be avoided. Some other preventive measures are dietary salt restriction, use of topical NSAIDs/non-pharmacological therapies and use of calcium channel blockers for treating hypertension.

Molecular Dissection of Renal Ischemia-Reperfusion: Oxidative Stress and Cellular Events.

Ischemic reperfusion kidney injury (IRKI) is a complex pathophysiological event, which is the most common cause of the acute kidney injury. The key characteristic of IRKI is a reduction in glomerular filtration rate, which implies an underlying impairment in hemodynamic regulation. In recent decades, convincing evidence illuminated the molecular and pathological events in the acute kidney injury, revealing the role of ischemia/reperfusion, oxidative stress, apoptosis, inflammation, fibrosis and changes in gene expression which activate different signaling pathways. The cascade of inflammation events is a key mediator of IRKI, which includes the inflammation process, complement activation and mobilization of innate immunity. Oxidative stress represents the increased presence of various free radicals that cannot be buffered by the antioxidant capacity which comprises of enzymatic and non-enzymatic components. Renal tissue injury during ischemia/reperfusion comes as a result of membrane lipids peroxidation, oxidative damage of proteins and DNA and results in apoptosis and necrosis. It is evident from many studies that augmentation of the antioxidant defense mechanisms has a protective role on kidney tissue. In recent years, the importance of heat-shock proteins and MicroRNAs in the pathogenesis of IRKI has been revealed and there are promising indications that in future they could serve as diagnostic biomarkers or therapeutic targets. Striking changes in global gene expression were shown, providing a great potential for fundamental understanding and clinical management of IRKI. The clinical outcome among patients with kidney transplantation will have the furthermost advance from the better understanding of the underlying molecular pathology of IRKI.

The attitudes of medical students towards rare diseases: A cross-sectional study.

Background/Aim: Rare diseases are chronic, degenerative and may lead to permanent disability. We aimed to assess knowledge and attitudes of the 3rd and 6th year medical students towards the treatment of rare diseases in Serbia. Methods. In this cross-sectional study, two samples of students were questioned for a survey: 350/446 (78.48%) students of the 3rd year, and 242/517 (46.81%) students of the 6th year. Methods: In this cross-sectional study, two samples of students were questioned for a survey: 350/446 (78.48%) students of the 3rd year, and 242/517 (46.81%) students of the 6th year. Results: Sixth year students estimated that they were more informed on the issue analyzed than the 3rd year students (median value of 4 and 3, interquartile range of 3-5, and 1-4, respectively; p < 0.05). However, a significant percentage of participants estimated incorrectly the prevalence of rare diseases according to the European Union standards (3rd year - 42.68%, 6th year - 49.55%). Core curriculum subjects were the main source of information on rare diseases (3rd year - 63.14%; 6th year - 92.14%). Our participants agreed that the most important problems are the following: high drug prices, difficult access to drugs and lack of public information. Students found, without any differences, that community access to effective drugs for rare disease should be improved (median value - 10, interquartile range 8-10 in both groups, p < 0.05). In order to improve pharmacotherapy of rare diseases in Serbia, the participants suggested establishment of a National Plan for Rare Diseases, approval of more appropriate drugs, simplified access to appropriate medicines, and more rapid diagnostics. Conclusion: It is necessary to improve the knowledge and attitudes of medical students towards pharmacotherapy of rare diseases. [Projekat Ministarstva nauke Republike Srbije, br. 175023]

Kidney Injury Molecule-1 and Cardiovascular Diseases: From Basic Science to Clinical Practice.

Despite the recent findings concerning pathogenesis and novel therapeutic strategies, cardiovascular disease (CVD) still stays the leading cause of morbidity and mortality in patients with renal dysfunction, especially acute kidney injury (AKI). Early detection of patients with impaired renal function with cardiovascular risk may help ensure more aggressive treatment and improve clinical outcome. Kidney injury molecule-1 (KIM-1) is a new, promising marker of kidney damage which is currently the focus of countless studies worldwide. Some recent animal and human studies established KIM-1 as an important marker of acute tubular necrosis (ATN) and reliable predictor of development and prognosis of AKI. Food and Drug Administration (FDA) in USA acclaimed KIM-1 as an AKI biomarker for preclinical drug development. Recent data suggest the importance of monitoring of KIM-1 for early diagnosis and clinical course not only in patients with various forms of AKI and other renal diseases but also in patients with cardiorenal syndrome, heart failure, cardiopulmonary bypass, cardiothoracic surgical interventions in the pediatric emergency setting, and so forth. The aim of this review article is to summarize the literature data concerning KIM-1 as a potential novel marker in the early diagnosis and prediction of clinical outcome of certain cardiovascular diseases.

Acute pretreatment with chloroquine attenuates renal I/R injury in rats.

BACKGROUND: Acute kidney injury (AKI) still remains an unresolved problem in pharmacotherapy and renal inflammation is a major factor in its development. Chloroquine, a well-known antimalarial drug, posses pleitropic effects as well: antiinflammatory, anticoagulant and vascular actions. The effects of chloroquine on renal function may involve significant increase in urine flow rate, glomerular filtration rate and sodium excretion, as well as stimulation of nitric oxide synthase. However, its role in experimental models of renal I/R injury is unknown. We aimed to analyze the acute effects of a single-dose intravenous chloroquine administered at three different times in the experimental model of I/R injury in rat. METHODS: Rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion with saline lasting 4 hours. Chloroquine was administered in doses of 0.3 mg/kg i.v. and 3 mg/kg i.v. 30 min before ischemia, 30 min before reperfusion and 5 min before reperfusion. Selected a hemodynamic, biochemical and morphological parameters were followed in the Sham-operated animals and rats subjected to I/R injury and pretreated with saline or chloroquine. RESULTS: Chloroquine (0.3 and 3 mg/kg, i.v.) protected the I/R injured kidney in an U-shaped manner. Both doses were protective regarding biochemical and histological markers of the I/R injury (serum urea, creatinine and fractional excretion of sodium, as well as total histological score, tubular necrosis score and KIM-1 staining score) (P<0.05 vs. corresponding controls, i.e. rats subjected to I/R injury and treated with saline only). The protective effects of the lower dose of chloroquine were more profound. Time-related differences between pretreatments were not observed (P>0.05, all). CONCLUSION: Our study shows for the first time that a single dose of chloroquine (0.3 mg/kg i.v.) could afford significant protection of the injured rat kidney.