Volume 8, Issue 4

Melatonin is a hormone produced by the pineal gland. In addition to its hormonal effect, it has strong antioxidant properties. Melatonin is probably best known for its ability to control circadian rhythm; it is sold in many countries as a supplement or drug for improving of sleep quality. However, melatonin’s effect is not limited to control of circadian rhythm:. it is involved in other effects, including cell cycle control and regulation of several important enzymes, including inhibition of inducible nitric oxide synthase. Melatonin affects immunity as well. It can modulate the immune response on disparate levels with a significant effect on inflammation. The role of melatonin in body regulatory process is not well understood; only limited conclusions can be drawn from known data. The current review attempts to summarize both basic facts about melatonin’s effects and propose research on the lesser known issues in the future.

In this review we show and describe a concept of designing autonomously moving artificial cells (chemical robots) carrying drugs and having tactic behavior based on artificial chemotaxis. Such systems could help to provide new and more efficient drug delivery applications. Chemical robot can be constructed based on the self-organization — natural “bottom-up” way — of fatty acid or lipid molecules into ordered nano- or micrometer size objects that have the ability to move and respond to environmental stimuli. The idea of using tactic carriers in drug delivery applications can be justified by the fact that cancer sites in the living body have different physiological characters (lower pH and higher resting temperature) compared to normal cells. The proposed “bottom-up” design method for self-propelled objects at small scales for targeted drug delivery applications could realize the original designation of nanoscience proposed 50 years ago by Richard Feynman.

This article reviews a population pharmacokinetics studies conducted during the past few years in Serbia. Studies have included three the most frequently used antiepileptic drugs (valproate, carbamazepine and lamotrigine) and different populations of epileptic patients: children, adults and heterogeneous population composed of both children and adults. The review compares obtained values of population pharmacokinetic models of clearance of these drugs, and factors that are significantly determined, making brief comments on the results of other authors on the same topic. Individualization of drug dosage is the basis of rational therapy, and factors of variability will always be subject of scientific research.

The acetylsalicylic acid (ASA) treatment is widespread therapeutic strategy in cardiology clinics. On the other hand, patients with heart diseases represent a significant group of cases in dental clinics. Accordingly, we studied the local hemostatic thrombus formation after dental tooth extractions (n=47) and other oral surgery treatment (n=13) in 60 patients with heart disease being on ASA therapy without drug discontinuation. In the control group free of ASA therapy it was: (n=24) and (n=6), respectively. In all studied patients, the aggregative activity of blood platelets by PFA-100 analyzer was assessed. It was found that 61.7% patients treated with ASA presented inhibition of platelets aggregation. Unexpectedly, in 35% of such patients, platelet aggregation function remained unchanged. In the control group, normal platelet aggregation was found in all subjects. It has been shown that ASA therapy has neutral effects on both thrombus formation and pain complications in patients with heart disease underwent tooth extraction and other oral surgery. Thus discontinuation of ASA therapy before surgery seems to be weakly validated.

Hemorrhagic complications are recognized when anti-platelet agents are used during or after surgical procedures. We present a 69-year-old male patient who developed hemothorax after chest tube insertion for pneumothorax as a complication of clopidogrel and aspirin following ischemic heart disease. Hemothorax associated clopidogrel has rarely been reported and this is the first academic publication of this complication type following chest tube insertion shortly after the cessation of clopidogrel. Our case demonstrates the possibility of hemothorax when chest tube insertion is indicated under such conditions.

Aims. To devise a scoring system for clinical variables related to positive findings at relaparotomy in secondary peritonitis. Methods. We have retrospectively studied 195 cases of patients after relaparotomy. According to the operation’s findings, the patients were divided into two groups: ‘relaparatomy unnecessary’ group A, ‘relaparotomy necessary’ group B. 6 factors (age, sex, leukocyte count, C reactive protein, time of symptoms to index operation, Mannheim Peritonitis Index) were evaluated in respect to their significance in decision making for relaparotomy. The predictive value for positive operation`s findings of these factors was evaluated by logistic multivariate regression analysis. According to this model a risk scoring system was created to support the decision whether to perform a relaparotomy. Results. Relaparotomy was unnecessary (Group A) for 154 (79,0%) patients, for 41 (21,0%) it was necessary (Group B). Comparing the groups A and B, we found a significant difference in patients’ mean age (54 v. 63 years, p=0,002), mean CRP level (133,2 v. 182,8 mg/L, p=0,025), mean time of symptoms to index operation (38,1 v. 67,1 hours, p=0,006) and mean MPI value (22,4 v. 29,4, p<0,0001). According to the above-mentioned predictors, a scoring system was devised: −0,17-(0,003×patient’s age years)+(0.153×time of symptoms to index operation hours)-(0,297×MPI)+(0,192×CRP mg/l). The score was 24,798±25,593 in group A and 36,572±32,543 in group B(p=0,028). Conclusions: Scoring system was devised to assist in creating treatment strategy after secondary peritonitis. If the score is ≥37, a planned relaparotomy should be performed. If the score is ≤24, other diagnostic and therapeutic tactics should be applied.

Aim. A residual mediastinal thyroid (“forgotten goiter”) is a well-known, though uncommon, complication of total thyroidectomy. Materials of study. The authors analyze their experience with three cases of goiter forgotten, observed in a series of 2946 thyroid resections in the period 2005–2010. In the study, a preoperative CT of the chest with three-dimensional reconstruction was always performed to examine the topographical relationships of the lesion. Excision was performed through cervicotomy, cervicosternotomic approach and cervicosternotomy, and posterolateral right thoracotomy. Results. There were no complications. Histological examination was suggestive of malignancy in one case (follicular carcinoma with pulmonary metastases). Discussion. The indication for surgery in cases of forgotten goiter is intrinsic to the diagnosis. Preoperative evaluation with accurate topographic imaging is required in all cases in order to understand the nature and location of mediastinal pathological tissue and to identify the most suitable access route. The cervicotomy is the ideal access for low surgical trauma and is easily extendable into a partial or complete sternotomy. A thoracotomy, on the other hand, which is usually reserved for the right side, must be planned preoperatively.

The presence of pericardial effusion in neonates usually indicates a poor prognosis. Here, we report a case of isolation of cardiac tamponade in a newly born. This may be related to vertical human parvovirus B19, an infection with atypical clinical manifestation. Any neonate with unexplained fetal pericardial effusion should always be tested for parvovirus B19 infection, even in the absence of known and proved fetal exposure. Despite the etiology of a tamponade the only reasonable procedure is a surgical evacuation during diagnosis.

The results of conducted research studies suggest that heredity and early fetal and neonatal development play a causal role in autism. The objective was to determine a relationship between pre-, peri-, and neonatal factors and autism. The relationship between genders and individual risk factors for autism was also examined. A case-control study was conducted among 288 children (96 cases with childhood or atypical autism and 192 controls individually matched to cases by the year of birth, sex, and general practitioners). Data on autism diagnosis and other medical conditions were acquired from physicians. All other information on potential autism risk factors were collected from mothers. Autism risk was significantly higher when mothers were taking medications (OR=2.72, 95%CI: 1.47-5.04) and smoked during pregnancy (OR=3.32, 95%CI: 1.12-9.82). It was also significantly associated with neonatal dyspnea (OR=3.20, 95%CI: 1.29-8.01) and congenital anomalies (OR=7.17, 95%CI: 2.23-23.1). In gender analysis only congenital anomalies were significantly associated with autism for girls but all of mentioned factors stayed independent risk factors for boys.

Omphalocele is the most common congenital defect of the abdominal wall and in a large percentage of cases it is associated with chromosomal anomalies. In this case report during the regular ultrasound examination at 11 weeks of gestation, omphalocela, whose scope was 90% of fetal abdomen, was diagnosed. Karyotype analysis showed the presence of chromosomal aberrations 47 XX + 18 (Edwards syndrome). After the presentation of the severity of congenital anomalies and characteristic of the Edwards syndrome patient decided to terminate the pregnancy.

Ultrasound of uterine scar after cesarean and measurement of its thickness can be used to evaluate its healing and risk factors for scar defect and uterine rupture. However, we believe that a period of up to 6 months after surgery is necessary to achieve complete healing of the scar, especially in cases of cesarean performed during labor.

Nucleus accumbens (NAcc) are a collection of neurons that form the main part of the ventral striatum, which is a significant dopaminergic structure. Also, NAcc is thought to play an important role in reward, pleasure, laughter, addiction, aggression, fear, and the placebo effect. In the present work we were interested in studying the effects of a 6-OHDA induced lesion in the nucleus accumbens (NAcc), which is known as an important dopaminergic structure, on a specific behavioral task that involves both short term and long term spatial memory (the radial-8-arm-maze task), as well as on the oxidative stress markers (two antioxidant enzymes: superoxide dismutase-SOD and glutathione peroxidase-GPX and a lipid peroxidation marker: malondialdehyde-MDA, as well as the total antioxidant status-TAS) from the temporal lobe, which is considered to be the most vulnerable cortical area to oxygen levels fluctuations and hypoxia. Our results showed some significant effects of this lesion on the reference memory errors and time necessary to finish the test in the radial-8-arm-maze task. Additionally, increased oxidative stress status was demonstrated in the temporal lobe of the lesioned rats, as demonstrated by the high levels of lipid peroxidation and decreased total antioxidant status. Moreover, significant correlations are reported here between the behavioral parameters which we studied in the radial-8-arm-maze task and the aforementioned oxidative stress markers.

Corticobasal syndrome (CBS) is a progressive disease that includes a heterogeneous neuropathological spectrum. In the majority of cases, corticobasal degeneration (CBD) is the underlying disease. Clinical heterogeneity is reflected in the clinical presentation of the syndrome and consequently misdiagnosis is common. Our case is of interest because the symptoms, the poor response to L-dopa and the I123 Ioflupane CIT SPECT (DAT-SCAN) results were typical for CBD. However, the magnetic resonance imaging appearance suggested the possibility of a disease of vascular etiology. A 63-year-old woman presented in our outpatient clinic with symptoms of progressive clumsiness in the right arm when performing movements demanding fine motor skills, and mild speech difficulties. The brain magnetic resonance imaging (MRI) report described ischemic lesions in the left subcortical parietal areas, in the centrum semiovale, in periventricular white matter, cingulated gyrus bilaterally and moderate ventricle dilatation. A comprehensive neuropsychological study suggested mixed cortical and subcortical involvement. A DAT-SCAN examination showed a diminished dopamine transporter uptake in the left lenticular nucleus, suggesting parkinsonisn. For this patient, CBS-CBD was the most probable diagnosis, whereas vascular CBS was not excluded. This case report illustrates the low diagnostic sensitivity in predicting CBD and the overlap with other related neurodegenerative diseases. Finally, it demonstrates that in CBS, different underlying pathologies can be found at the same individual.

The study aimed to determine characteristics of addicts on methadone maintenance therapy (MMT), which are related to the level of social functioning, with emphasis on the role of social support. In a prospective study, opiate addicts (n=150) who were on MMT completed the Pompidou questionnaire, the Social Adaptation Self-evaluation Scale (SASS) and the Multidimensional Scale of Perceived Social Support (MSPSS). Statistical data processing was based on testing the difference between features that best distinguish subgroups of addicts who were dissatisfied, moderately satisfied and satisfied with their social functioning. Opiate addicts up to 30 years of age had a statistically higher score on SASS scale than addicts over 30; addicts who are dissatisfied are mainly unemployed and have average or above-average family/community financial status; opiate addicts who were moderately satisfied with their social functioning were three years or longer on MMT; paradoxically, the highest mean value of score on MSPSS scale dominated among addicts who are dissatisfied with their social functioning. These results indicate that age, employment, financial status, duration of MMT are the characteristics of addicts which are related to the level of social functioning. Social support is most perceived by addicts who are dissatisfied with their social functioning.

Unrecognized and untreated Borrelia infection can progress from localized inflammation (erythema migrans) to early or late generalized stage within weeks to months. Meningoradiculitis, arthritis, multiple erythemas, myositis, and myocarditis of the early generalized stage have a good prognosis after antibiotic treatment, but late manifestations can progress to chronic disease. Phrenic nerve palsy, autonomic nervous system dysfunction and carditis with acute heart failure are among rare manifestations as well as late generalised stage with myelitis. We present a case of a patient with meningoradiculitis, autonomic nervous dysfunction, respiratory failure due to phrenic nerve palsy and acute heart failure with systolic myocardial dysfunction. The diagnosis of Borrelia infection was confirmed by positive serological testing, appropriate response to antibiotic therapy and exclusion of other diseases. Our case suggests that in unexplained respiratory failure and acute systolic myocardial dysfunction, particularly associated with signs of meningoradiculitis, Borrelia infection should be included in the differential diagnosis.

Alzheimer’s disease is characterized by the accumulation and deposition of Aβ peptides in human brains. Aβ peptides are toxic to neurons by lots of mechanisms of which Aβ induced oxidative stress is one of the hypothesis. The present study aimed to determine the effect of Hyperbaric oxygen (HBO) on Aβ25–35 induced cognitive deficits and oxidative stress and apoptosis effects in rats. Rats were given an injection of aggregated Aβ25–35. After treatment with HBO for 20days, the learning and memory ability, hippocampus neuronal apoptosis, the activity of SOD, GSH content and the MDA level and mRNA and proteins expression of Bcl-2 and Bax were detected. Our results demonstrated that HBO could significantly improved the apoptosis hippocampus neuronal induced by Aβ25–35, involving the improvement of the learning and memory impairment, which accompanied of increasing the gene and protein expression of bcl-2 and enhancing the activity of SOD and GSH content. These findings suggest that treatment of HBO might prevent the Aβ25–35 induced learning and memory impairment by increasing the gene and protein expression of bcl-2 and enhancing the activity of SOD and GSH content to alleviate the apoptosis hippocampus neuronal. This suggests that HBO may be a potential therapeutic agent for AD.

The characterization of wear particles is of great importance in understanding the mechanisms of osteolysis. In this unique study, thirty-one tissue samples were retrieved at revision surgeries of hip implants and divided into four groups according to the composition of metal prosthetic components. Tissue samples were first analyzed histologically and then by scanning electron microscopy (SEM) combined with back-scattered electron imaging and energy dispersive X-ray spectroscopy. Therefore, particles were studied directly in situ in tissue sections, without the requirement for particle isolation. The composition of metal wear particles detected in the tissue sections corresponded to the composition of the implant components. A considerable number of large metal particles were actually clusters of submicron particles. The clustering of submicron particles was observed primarily with CoCrMo (cobalt-chromiummolybdenum) and, to a lesser extent, for stainless steel particles. SEM secondary and back-scattered electron imaging was an appropriate and selective method for recognizing the composition of metal particles in the in situ tissue sections, without destroying their spatial relationship within the histology. This method can be used as a screening tool for composition of metal and ceramic particles in tissue sections, or as an additional method for particle identification.

Introduction. Bilateral massive adrenal hemorrhage (BMAH) is a rare catastrophic condition that manifests with acute adrenal insufficiency. Death can occur within a few hours or after many days. BMAH in association with fulminant septicemia and sepsis occurring in children and young adults is also known as the Waterhouse-Friderichsen syndrome. Fulminant sepsis associated with purpura is lethal in 40–70% of patients. Case report. The abrupt onset of fever with sore throat occurred in a 20-year old man. Next day in the early morning, he complained of severe symptoms: generalized weakness, shortness of breath and myalgia. Few hours later petechial rash occur. Within 30 hours from first symptoms he died in hospital. On autopsy, there were macroscopic bilateral areas of adrenal hemorrhage. Autopsy also revealed hemorrhage in almost all organs and tissues. Microbiological blood culture and toxicological finding was negative. Discussion. In our case, very high levels of procalcitonin and D-dimer, with all other clinically and autopsy findings, was directing medical examiners that a main cause of death was fulminant bacterial sepsis. Blood culture did not reveal any bacteria, so the cause of BMAH stays uncovered. The bacteria that most often cause fulminant sepsis connected with BMAH and death within 12–24 hours from first symptoms is N. meningitidis. It is very likely that N. meningitidis caused BMAH in our case, but it will stay in domain of speculation.

A 78-year-old Japanese man with a 5-day history of fever (∼38°C) and decreased appetite was admitted to our hospital. Transesophageal echocardiography revealed aortic valve vegetation. Streptococcus constellatus was detected from a blood culture. An antibiotic sensitive to this strain was administered for 6 weeks, and the patient has been well for 6 months without any sign of relapse. A review of all documented cases of infective endocarditis due to S. constellatus revealed nonspecific initial symptoms, especially coughing, and complications of abscess formation and septic embolisation. Clinicians should carefully consider the choice of antibiotic agents in the treatment of infective endocarditis due to S. constellatus, because penicillin-resistant strains have been documented in some cases.

The aim of this study was to determine the prevalence of chronic disease and the risk factors for herpes zoster infection. In this case-control study medical records were collected from 55 patients who presented with herpes zoster and 54 patients in a control group who presented with gastroenterocolitis. Both groups were treated at the Clinic for Infectious Diseases, University Clinical Hospital Mostar from January, 2005 to December, 2010. When we compared the herpes zoster group with the control group, we did not demonstrate any significant difference in the overall prevalence of chronic diseases. However, the prevalence of diabetes and cancer was statistically higher when compared to the control group. A statistically significant difference in the number of cigarette smokers was not observed, whereas the number who consumed alcohol in the herpes zoster group was significantly higher compared to the control group. The correlation between alcohol and herpes zoster could help in solving the reactivation mechanism of VZV.

A previously healthy 40-year-old male presented with a 2-week history of fever and abdominal discomfort that was resistant to empirical broad-spectrum antibiotic treatment. The patient’s blood cell count and complete biochemical panel was normal, except for an increased lactate dehydrogenase level. Ultrasonography and computed tomography of the abdomen showed a large, soft tissue mass had infiltrated superior part of the spleen. Splenectomy with total tumor mass removal were performed. The pathological examination of the tumor tissue confirmed diagnosis of isolated myeloid sarcoma with monoblastic differentiation. Despite intensive antileukemic therapy, patient died four months after diagnosis was established.

The aim of the study was to evaluate the effects of hyperglycemia on nerve conduction in patients with newly diagnosed diabetes mellitus type 1, and to investigate the significance of early electrophysiological diagnostics in these patients. The study included 85 newly disclosed patients with type 1 diabetes mellitus, in the first three months after the disease. Nerve conduction velocities (NCV) of further nerves were evaluated: median, peroneal, tibial and sural nerve as well as late responses (F-wave and H-reflex). Metabolic control parameters that were evaluated included: glycemia rate on the day of investigation and HbA1c. All patients had poor metabolic control parameters. We found NCV slowing predominantly in the tibial nerve (in 82.4% of patients). Prolonged F-wave latency was disclosed in 72.9% of patients, while H-reflex was evoked in 27.1% of patients only. The most sensitive parameter in the early neurophysiologic diagnostics was the measurement of F-wave latency. Our study underline the significance of early neurophysiological diagnosis, since hyperglycemia can play an acute role in NCV slowing, despite the absence of clinical symptoms, particularly in the first three months after the diagnosis has been confirmed.

The health-promoting effects of antioxidant vitamins C and E supplementation are unclear. This study investigated the effects of vitamins C and E on the activities of reactive oxygen species (ROS)-scavenging enzymes and protein and lipid peroxidation statuses under resting and exercise-induced conditions. Thirteen healthy, previously untrained males (age 20–21 years) participated in this study. Seven subjects performed physical exercise using a cycle ergometer, and six performed a 6-min walk test (6MWT) prior to vitamin administration and after 1-week oral administration of vitamin C (1000 mg/day) and vitamin E (300 IU/day). Venous blood samples were collected before and after exercise. Plasma vitamin C concentration, superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and protein carbonyl and thiobarbituric acid-reactive substance (TBARS) contents were measured. Antioxidant supplementation increased vitamin C concentration by 34% (p<0.05), decreased SOD activity by 17% (p<0.05), increased GPx activity by 13% (p<0.05), and increased the GPx/SOD activity ratio by 37% (p<0.05). Protein carbonyl and TBARS contents were unaffected. Antioxidant vitamins effectively increase the plasma GPx/SOD activity ratio, but fail to reduce protein carbonyl levels induced by exercise.

The work was dedicated to investigation of dynamics of epileptic activity in conditions of extremely high frequency electromagnetic waves (EHF) radiation (7,1 mm, 0,1 mW/cm2) upon focal epileptic activity. Epileptic activity was penicillin-induced (10,000 IU/ml) in the frontal region of the brain cortex in myorelaxed and artificially ventilated rats under acute experimental condition. Thermal effects were absent as far as absorbed dosage of energy did not exceed 0,1 J/ animal. It was established that preliminarily performed hypogeomagnetic period (3,0 h) with the inductivity of geomagnetic field at 5×10−8 Tesla caused the intensification of antiepileptic effects of EHF (15,0 min of exposure). It was pronounced in the form of decrease of foci intensity and significant reduction of lifespan of foci — up to 115,3±13,4 minutes, which was both significant when compared with separate effects of hypogeomagnetic influence (187,3±12,5 min) and EHF (15,0 minutes of exposure) effect (164,2±12,5 minutes) (P<0,05). Besides, EHF (15,0 min) which was made after 3,0 h exposure to hypogeomagnetic influence suppressed generalized seizures in amygdalarly kindled rats.

The toxic potential of the endodontic sealers ingredients, especially the unreacted monomer, that can irritate the periapical tissue and interfere with the healing process, thus having a negative impact on the biocompatibility of the material. The aim of this study was to evaluate the influence of three experimental endodontic sealers on cells viability in vitro. Human umbilical vein endothelial cells (HUVEC) were used. The experiments were done with solid samples and extracts of sealers in artificial saliva and water. The experiments evaluated the cytotoxicity of the residual monomers that resulted from the tested composites. The decrease in cell viability was quantified by colorimetric measurement of formazan. The components of the sealers dissolved in artificial saliva and water were determined by high performance liquid chromatography (HPLC). The HUVEC are a novelty for testing the endodontic sealers biocompatibility, with certain advantages compared to other cell types used in the literature, e.g. HELA cells, fibroblasts. The data showed that cytotoxicity was directly linked with the unreacted monomer — 2-hydroxyethyl methacrylate (HEMA) present in these composites. Two of the three formulations had little or no cytotoxic effect, which makes them suitable for further testing in order to be used in endodontic treatment.