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Objective: To establish the association between serum levels of reactive oxygen species (ROS) products, nitric oxide (NO) radicals and ascorbate radicals with renal resistive index (RRI), common carotid artery resistive index (CCARI) and intima-media thickness (IMT) in gout patients, and to find out whether the connection is more pronounced when tophi are present.

Methods: A cross-sectional study including 71 consecutive gout patients, divided into two groups according to the presence of subcutaneous tophi. Serum concentrations of ROS products, NO radicals and ascorbate radicals were determined by ex vivo electron paramagnetic resonance (EPR) study. RRI was measured in both kidneys at the level of interlobar arteries with 3.5 MHz transducer. By applying ultrasound of the common carotid arteries, conducted with 10 MHz linear transducer CCARI and IMT were measured.

Results: Gouty arthritis without tophi and gouty tophi subjects were age-matched. Serum uric acid and distribution of conventional cardiovascular risk factors was equal in the groups. However, in tophi patients CRP and the number of individuals who had suffered a cardiovascular event were higher. In the two stages of the disease serum levels of ROS products, NO radicals, ascorbate radicals, as well as RRI and CCARI were comparable but intima-media was thicker in gouty tophi. Serum concentrations of ROS products, NO radicals and ascorbate radicals did not correlate with RRI, CCARI and IMT. Among untreated and treated with Allopurinol or Febuxostat patients the means of ROS products, NO radicals, ascorbate radicals, RRI, CCARI and IMT were similar.

Conclusions: In the earlier and advanced stage of the disease we found no difference in oxidative stress level but the degree of inflammation was higher in tophi subjects. No connection was established between serum ROS products, NO radicals and ascorbate radicals with renal and carotid arteries arteriosclerotic vascular changes. We suggest that in gout individuals intrinsic inflammation has a leading role in the process of atherogenesis.


Takayasu arteritis is a chronic, progressive, idiopathic, large-vessel vasculitis that affects the aorta, its main branches and the pulmonary arteries. It typically occurs in young Asian women but can be found in any ethnic group and in men. The disease is named after Mikito Takayasu, a Japanese ophthalmologist, who first described the arteriovenous anomalies in the retina of a patient with the disease in 1908. The etiopathogenesis is not known, but studies are being conducted regarding the immunological, infection and genetic aspects of the disease. Early during the course of the disease, inflammation of the involved arteries progresses, resulting in segmental stenosis, occlusion, dilatation and/or aneurysm. The clinical presentation of Takayasu arteritis varies depending on the blood vessels involved. Early symptoms are nonspecific, making the diagnosis difficult. Subsequently, arterial occlusions occur, producing more specific ischemic symptoms. Paucity of specific symptoms and laboratory biomarkers, as well as difficulties in assessing the disease activity and progression, make it often unrecognized at onset, and its activity is frequently underestimated. The diagnosis is usually confirmed by a combination of clinical manifestations, laboratory markers, diagnostic criteria and imaging methods. The purpose of this review is to address the current knowledge on pathogenesis, investigations, classification and management, and to emphasize the need for timely diagnosis, effective therapeutic intervention, and close monitoring of this disease.


GABAB receptors are G-protein-coupled receptors, playing a very important role in the regulation of many physiological processes. The GABAB signaling pathway could modulate neurotransmission processes at the level of the preoptic area in the anterior hypothalamus, which is thought to function as the thermoregulatory center. The present study was performed to investigate the effects of GABAB agonists and antagonists on core body temperature of rats with normal weight and diet-induced obesity. The results showed that systemic administration of the GABAB antagonist CGP35348 induced significant hyper-thermia in rats with normal weight, whereas the GABAB agonist baclofen led to a decrease in body temperature. The effects of baclofen and CGP35348 on body temperature were less pronounced in rats with diet-induced obesity compared with those with normal weight. Presently it remains unclear how obesity affects the GABAB receptor function at the level of the central thermoregulatory system.


Aim: To study the differences in cardiovascular risk between type 2 diabetic and non-diabetic patients with asymptomatic hyperuricemia and gout using the Framingham Risk Score (FRS) and complex multimodal ultrasonography.

Patients and methods: A total of 201 patients participated, divided into two groups: 1/ patients with asymptomatic hyperuricemia (n = 52), and 2/ patients with gout (n = 149). FRS was determined as well as ultrasound parameters, independent predictors of cardiovascular risk: left atrial size (LA), intima-media thickness (IMT) and common carotid artery resistive index (CCARI).

Results: The patients in the two groups were age-matched and conventional cardiovascular risk factors were equally distributed. In the asymptomatic hyperuricemia group, 12 patients (23.1%) had diabetes. In this group, there was no difference in FRS between diabetic and non-diabetic individuals. However, diabetic patients had larger LA, thicker intima-media and higher CCARI. In the gout group 18 subjects (12%) had diabetes, but the FRS, LA, IMT and CCARI values were similar among diabetic and non-diabetic patients. Furthermore, when gout subjects were subdivided according to the presence of tophi, we found that the subgroup having gouty tophi and diabetes had larger LA (p = 0.014) compared to those with gouty tophi without diabetes.

Conclusion: In diabetic patients with asymptomatic hyperuricemia and gouty tophi, a more complex approach for estimation of cardiovascular risk is needed. Our work suggests that diabetes and tophi might potentiate their action on the cardiovascular system.


Objective: Graves’ disease (GD) is characterized by elevated TSH-receptor antibodies (TRAb) and less often – thyroid peroxidase (TPOAb) and thyroglobulin antibodies (TgAb). Our aim was to examine the hormonal and ultrasound characteristics of patients with newly diagnosed GD with differing positive thyroid antibodies.

Materials and Methods: This study included 249 patients with newly diagnosed GD (191 women, 58 men). 40.2% of them had Graves’ ophtalmopathy. The serum levels of TSH, free T4, free T3, TRAb, TPOAb, and TgAb were measured with third generation ECLIA assays (Roche Diagnostics, Switzerland). Thyroid ultrasound was performed with a Fukuda-Denshi 550 device (Fukuda Corp., Japan) and an Ultrasonix device (Ultrasonix Medical Corp., Canada). Statistical analyses were done using the SPSS 23.0 statistical package (Chicago, IL).

Results: 64% of the patients were TPOAb+ and 36% − TgAb+. One third were only TRAb+, 1/3 had two positive antibodies (TRAb + second antibody) and 1/3 – all three positive antibodies. Patients with more positive antibodies tended to be younger, had higher fT4, TRAb levels, thyroid volume but rarely had nodules on US and accompanying GO. Positive TPOAb antibodies were found in younger patients, with higher fT4 and TRAb levels, higher thyroid volume and lower prevalence of nodules and GO. The same trends were found in patients with positive TgAb.

Conclusion: The different characteristics of GD patients with varying thyroid antibody profiles may be due to a variation in the pathogenesis of the disease. An individualized clinical approach may be suitable in those cases.


The extraction of mandibular third molars is a traumatic procedure accompanied by marked clinical symptoms in the postoperative period. The aim of the present study was to determine the effects of the removal of a partially impacted mandibular third molar on the masticatory efficiency in patients in the early postoperative period.

Material and methods. A total of 47 participants, divided into two groups, took part in this pilot study. The first group included 33 patients with a mean age of 18.3 years (SD = 0.9 years), defined as the Control group; the second group involved patients with a mean age of 33.3 years (SD = 1.86), referred to as the Clinical group. The masticatory efficiency of the Clinical group patients was objectively double-checked using a Protab® test bite: once during the preliminary examination (prior to extraction of the wisdom tooth) and again 7 days after the surgical removal of the wisdom tooth. A sieve analysis was applied to determine the artificial test bite particle size and size distribution following mastication. Feedback on the Clinical group patients’ assessment of any subjective complaints was obtained through a questionnaire containing two questions considered relevant to patients’ masticatory efficiency. The data from the sieve analysis of each fraction were analyzed using the Statistics Software Package for Epidemiological and Clinical Research (IBM SPSS V.20.00).

Results. The data processing of all parameters tested prior to and after extraction of the wisdom tooth revealed statistically significant differences. Only the duration of chewing after the third molar extraction matched the chewing duration in the healthy control subjects (p = 0.198). The analysis of the feedback on the self-assessment of patients from the Clinical group demonstrated that prior to extraction all subjects (100%) experienced pain to a varying degree, whereas in half of the patients (50%) the pain disappeared following extraction. The Spearman’s test for correlation between mean particle sizes as well as the questionnaire feedback indicated a strong positive relationship with food trapping. Accordingly, the larger mean particle size was linked to the self-assessment of food trapping around the wisdom tooth prior to extraction (Spear-man’s Rho = 0.57, p = 0.032). There was also a correlation between the chewing time and the sensation of pain in the teeth adjacent to the extraction wound. The results suggested that the shorter duration of chewing was associated with a greater sensation of pain (Spear-man’s Rho = -0.61, p = 0.026).

Conclusion. The eruption of mandibular third molars causes difficulties in the masticatory process. A positive trend was observed towards normalizing of the chewing duration following extraction (t = -1.356, p = 0.198).


Background/objectives: Recent data suggest a role for heparanase in several proteinuric conditions. An increased glomerular heparanase expression is associated with loss of heparan sulfate in the glomerular basement membrane (GBM). The aim of the present study was to investigate the renal effects of heparanase inhibition in a diabetic experimental model.

Methods: Fifteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) controls, 2) diabetics (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetics + heparanase inhibitor (Sulodexide 1/5 mg/kg per day, gavage). The treatment started on the 21st day, for 21 consecutive days. The rats were kept individually in a metabolic cage (8 AM-2 PM) and urine samples were collected on the 21st and 42nd day. At study end blood, urine and tissue samples were collected for biochemical (blood BUN and Cr, urine GAG and Protein) and histological analyses.

Results: The results of this study showed that the heparanase inhibitor (sulodexide) significantly decreased urine GAG and protein excretion, urine protein/creatinine ratio and serum BUN and Cr in streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the DN rats having received the heparanase inhibitor (sulodexide).

Conclusion: Our data suggest that the heparanase inhibitor (sulodexide) is able to protect against functional and histopathological injury in DN.


Introduction: The total knee replacement is the definitive treatment for knee osteoarthritis (OA). It is an effective intervention to correct OA-related functional limitation. In such patients postoperatively are observed significant differences in the biomechanics of the two knee joints. While bearing the body weight the unoperated knee joint becomes very painful, stiff and incapable of neutral positioning. These factors significantly hamper the initial training in gait with aids in the standard locomotive stereotype immediately after surgery for knee joint replacement, where walking plays an essential role in daily activities and has varied health benefits.

Aim: The aim of the study was to check whether different types of gait with aids in the early postoperative period after total knee replacement have a different influence on the recovery process.

Material and methods: This study was conducted between January 2017 and July 2018 in the Department of Orthopedics and Traumatology of the University Hospital “Kanev” – Rousse. It included 56 patients with unilateral total knee replacement after gonarthrosis, divided into a control and experimental group, each of 28 patients. All patients in both groups had knee extension deficit of the untreated knee joint. The patients in both groups followed the same physiotherapy programs, performed from about the 2nd postoperative day to the 21st day when they were discharged from the department. The difference between the patients in both subgroups was their gait pattern with two axillary crutches.

Results and Discussion: There were statistically significant differences between both groups. One of the most significant differences was in ROM. In the experimental group patients, flexion was improved with an average of 20° more than in the control group patients. Also, in the operated joint, the patients in the experimental group had no contracture, whereas those in the control group showed 15° at the end of the follow-up period.

Conclusion: The results of the study show that the choice of gait training in the following order “crutches, operated leg, crutches, untreated leg” in patients with extensor deficiency and contracture in the untreated knee is more appropriate than the standard type of training in walking with aids.


Background: Atrial fibrillation is a relatively common complication of acute myocardial infarction with significant impact on the short and long-term prognosis.

Methods: A systematic literature review was done through Pubmed and CENTRAL to extract data related to new-onset atrial fibrillation following primary PCI.

Results: Searching resulted in twenty-one matched studies. Extraction of data showed an incidence rate of new-onset atrial fibrillation (2.8%-58%). A negative impact was found on the outcomes of patients treated with primary PCI with increased short and long-term mortality and morbidity.

Conclusion: New-onset atrial fibrillation is an adverse prognostic marker in patients with acute myocardial infarction treated invasively. Preventive measures and anticoagulant therapy should be considered more intensively in this subset of patients.


Nowadays, minimally invasive and non-invasive approaches in aesthetic medicine are increasingly popular and non-surgical rhinoplasty is one of the procedures with rising demand worldwide. In Bulgaria, this procedure seems to be uncommonly performed, since there are no reports in the local scientific literature. The aim of this preliminary study was to briefly explore the possibilities of hyaluronic acid (HA) fillers for correcting three of the most common nasal deformities – dorsal hump, under-projected and under-rotated nasal tip in primary cases. In order to accomplish this objective, a retrospective clinical study was conducted encompassing 11 cases of the authors’ practices with the above mentioned nasal irregularities and no previous surgical/non-surgical treatment. The analysis of patient-reported outcomes suggested a high satisfaction rate, with no major complication in the series. The HA filler has shown to be safe, relatively easily applicable and highly effective for camouflaging nasal deformities. A special emphasis was put on the patient safety and ten golden rules for staying out of trouble were given.