Efficacy and safety of general anesthesia with caudal block for inguinal hernioplasty in children: a randomized controlled trial.

OBJECTIVE: Caudal block is a type of regional anesthesia suitable for inguinal hernia surgery in children. Our goal was to determine the effectiveness of caudal block combined with general anesthesia in providing intra- and postoperative analgesia and its effect on hemodynamic stability and drug consumption. PATIENTS AND METHODS: Prospective, randomized controlled study included 78 boys, 3-5 years, with an indication for inguinal herniorrhaphy, divided into groups G (general anesthesia, n=39) and G+C (general anesthesia + caudal block, n=39). We monitored hemodynamic parameters intraoperatively, postoperative pain, and total consumption of all medicaments in the perioperative period. The monitoring of complications and side effects of drugs was also carried out. RESULTS: Boys in group G had statistically significantly higher values of heart rate in the 5th minute (p<0.01), in the 25th minute (p<0.01), and after awakening from anesthesia (p<0.01). We obtained similar results with systolic and diastolic pressure values in the 5th minute (p<0.01), 15th minute (p<0.01), 25th minute (p<0.01), before awakening from anesthesia (p<0.01) and after awakening (p<0.01). They also had significantly statistically higher total consumption of propofol, fentanyl, and acetaminophen (p<0.01). Boys in group G+C had significantly lower postoperative pain scores: initially (p<0.01), after 2 hours (p<0.01), and after 5 hours (p<0.01). No complications occurred in this group. CONCLUSIONS: In children, the combination of general anesthesia with caudal block, compared to general anesthesia only, is more efficient in suppressing visceral pain, leading to better hemodynamic stability, and reducing the consumption of medicines in the perioperative period.

Effect of different doses of remifentanil on the cardiovascular response after endotracheal intubation: a randomized double-blind study.

OBJECTIVE: Laryngoscopy and endotracheal intubation (EI) often provoke a marked sympathetic response, which leads to tachycardia and hypertension. The aim of this study was to investigate the effect of different doses of remifentanil on the cardiovascular response to laryngoscopy and EI. PATIENTS AND METHODS: 100 patients were included in this randomized study. The participants were divided into four groups of 25 patients each. The patients in the control group did not receive remifentanil. The patients from other three groups received remifentanil prior to induction of anesthesia at doses of 0.5 µg/kg, 1 µg/kg, and 1.5 µg/kg. Hemodynamic parameters were measured before and after administration of remifentanil, after induction of anesthesia and one minute after EI. RESULTS: After administration of remifentanil and induction of anesthesia, a decrease in arterial pressure and heart rate occurred in most patients. After EI, an increase in arterial pressure and heart rate was observed in most patients. The largest increase was recorded in the group of patients who did not receive remifentanil. The best hemodynamic response was observed in patients who received 1 and 1.5 µg/kg of remifentanil. CONCLUSIONS: Remifentanil at the doses of 1-1.5 µg/kg is absolutely safe for co-induction of anesthesia with thiopental. Such dosing regimen provides optimal conditions for reducing hemodynamic response to laryngoscopy and EI.

The role of tapentadol in cancer pain pharmacotherapy in patients with metastatic malignant disease.

OBJECTIVE: The aim of this study was to establish the effects of prolonged formulation of tapentadol in combination with palliative radiotherapy on bone metastatic changes in oncology patients with primary breast cancer and proven bone metastases. PATIENTS AND METHODS: The research was conducted as a prospective study at the Clinic for Oncology, University Clinical Center Nis, Nis, Serbia, during a three-month interval of monitoring the patients. The first group comprised 30 patients with mentioned malignancy for which tapentadol was prescribed, and they underwent palliative radiotherapy for bone metastatic changes. The second group comprised 30 patients with the same disease treated only with pain relief radiotherapy to metastatic changes. All the patients were interviewed using the Pain Detect questionnaire. RESULTS: Significantly more patients from the first group had severe pain in comparison to patients from the control group (χ2=16.596; p<0.001) at the second measurement and also at the third measurement (χ2=15.357; p<0.001). At the third measurement, pain with a neuropathic component was significantly more present in patients from the control group (χ2=8.541; p=0.014). There was a significant pain reduction in both groups - Tapentadol group (χ2=59.513; p<0.001) and control group (χ2=60.000; p<0.001) - and also a significant reduction of neuropathic pain component: Tapentadol group (χ2=56.267; p<0.001) and control group (χ2=60,000; p<0.001). There was a statistically significant positive correlation between tapentadol dose and pain intensity according to the numerical pain scale at all three measurements. CONCLUSIONS: Tapentadol prolonged-release formulation is an effective pharmacotherapy solution, along with palliative radiotherapy, for pain relief in patients with skeletal metastatic breast cancer. Palliative radiotherapy in these patients does not provide adequate neuropathic pain component relief.

Endometrial immunocompetent cells in proliferative and secretory phase of normal menstrual cycle.

BACKGROUND: Menstruation was presented as a result of inflammatory process. The total and relative numbers of the endometrial immunocompetitive cells vary during the different phases of the menstrual cycle. The aim of this morphological study is to make a contribution to understanding different distribution of leukocyte types during proliferative and secretory phase of normal menstrual cycle. MATERIALS AND METHODS: The study included 40 women (20 in proliferative and 20 in secretory phase of the menstrual cycle). Exploratory curettage performed as preoperative preparation due to uterine myomas. Immunophenotyping was performed by immunoalkaline phosphatase (APAAP) using monoclonal antibodies: CD15, CD20, CD30, CD45RO, CD56, CD57 and CD68. The results were statistically analysed using SPSS 20.0 software. RESULTS: Natural killer (NK) cells are dominant during secretory, and CD45RO T lymphocytes are dominant during proliferative phase of the menstrual cycle. During the secretory phase of menstrual cycle, leukocytes make 30% of total endometrial cells. NK cells (CD56+ bright subpopulation), activated T lymphocytes, macrophages and B lymphocytes significantly increase in their number during the secretory phase of menstrual cycle. CONCLUSIONS: Significant changes in endometrial leukocyte populations during proliferative and secretory phase of the menstrual cycle are emphasized. Changes in dominance of different leukocyte subpopulations are determined by hormonal and microenvironmental changes in modulatory factors that have not yet been fully explained.

Melatonin treatment prevents carbon tetrachloride-induced acute lung injury in rats by mitigating tissue antioxidant capacity and inflammatory response.

AIM: Carbon tetrachloride (CCl4) is an organic chemical that produces different tissue­damaging effects when ingested or inhaled. Present study aims to determine whether the application of exogenous melatonin, a neurohormone with numerous biological properties, can prevent disturbances in lung tissue antioxidative capacities and arginine metabolism, tissue inflammation and oxidative damage induced by exposure to CCl4 in rats. METHODS: The effects of melatonin on the changes occurring in rat lung tissue after an acute exposure to CCl4 were studied by monitoring alterations in antioxidant capacities, inflammatory parameters, parameters of arginine metabolism, and lipid and protein oxidative damage. RESULTS: The results indicated that melatonin prevents CCl4-induced lung damage by mitigating tissue antioxidant capacity and preventing nitric oxide production through a shift from nitric oxide synthase to arginase. Also, melatonin partially prevented tissue inflammation and molecules' oxidative modification seen after exposure to CCl4. CONCLUSIONS: The protective activity of melatonin can be attributed to its ability to scavenge both free radicals, as well as to its potential to increase tissue antioxidant capacity. The modulation of inflammatory response through both decrease in tissue inflammatory parameters and influence on arginine-nitric oxide metabolism might be an additional mechanism of action (Tab. 1, Fig. 2, Ref. 33).

Significance of the Ki-67 proliferation index in the assessment of the therapeutic response to cisplatin-based chemotherapy in patients with advanced cervical cancer.

OBJECTIVE: The purposes of this study were to examine the therapeutic response of advanced cervical cancer to Ki-67 proliferative index (Ki-67 PI) dependent cisplatin chemotherapy, and to determine Ki-67 PI referential value that is expected to provide a satisfactory therapeutic response of cervical cancer to cisplatin chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 59 patients treated for cervical cancer at Clinic for Oncology, Clinical Center Nis, Serbia. According to the obtained Ki-67 PI values, patients were divided into three groups, and all the patients received the same cytostatic, cisplatin. Therapeutic response to chemotherapy was evaluated in relation to disease progression presence or absence and progression-free survival after a year follow-up since the first chemotherapy. RESULTS: Survival rate increases with an increase of Ki-67 PI by Kaplan-Meier survival analysis, meaning that survival rate is statistically significantly shorter in the group of patients with Ki-67 PI < 40% in comparison to patients from other two groups (p=0.010). Mann-Whitney test confirmed a statistically significant increase in survival rate among the groups of patients formed according to Ki-67 PI (p<0.05). Kaplan-Meier survival analysis confirmed that the mean survival rate in the group of patients with Ki-67 PI values over 60% is statistically significantly longer in comparison to patients with Ki-67 PI values below or equal 60% (p<0.001). CONCLUSIONS: Advanced cervical cancer with a high Ki-67 PI expression responds better to cisplatin-based chemotherapy, thus resulting in a longer survival rate. The values of Ki-67 PI were determined: high Ki-67 PI (≥ 60%), moderate Ki-67 PI (40-60%), and low Ki-67 PI (≤ 40%).

Development of non-peptide ACE inhibitors as novel and potent cardiovascular therapeutics: An in silico modelling approach.

Angiotensin-converting enzyme (ACE) inhibitors have been acknowledged as first-line agents for the treatment of hypertension and a variety of cardiovascular disorders. In this context, quantitative structure-activity relationship (QSAR) models for a series of non-peptide compounds as ACE inhibitors are developed based on Simplified Molecular Input-Line Entry System (SMILES) notation and local graph invariants. Three random splits into the training and test sets are used. The Monte Carlo method is applied for model development. Molecular docking studies are used for the final assessment of the developed QSAR model and the design of novel inhibitors. The statistical quality of the developed model is good. Molecular fragments responsible for the increase/decrease of the studied activity are calculated. The computer-aided design of new compounds, as potential ACE inhibitors, is presented. The predictive potential of the applied approach is tested, and the robustness of the model is proven using different methods. The results obtained from molecular docking studies are in excellent correlation with the results from QSAR studies. The presented study may be useful in the search for novel cardiovascular therapeutics based on ACE inhibition.

Ascites in Ovarian Carcinoma - Reliability and Limitations of Cytological Analysis.

OBJECTIVE: The objective of this study was to examine the validity of ascitic fluid cytology in the detection of pathological findings, to examine the percentage of false positive and false negative results in the cytology of ascitic fluid and to determine the validity of peritoneal cytology in relation to the histopathological type of the ovarian tumour. METHODS: This retrospective study included 170 peritoneal cytology findings. The study was conducted from January 2010 to December 2012. The experimental group included 76 cytology findings obtained from patients diagnosed with ovarian carcinoma, whereas the control group was composed of 94 cytology findings of benign ovarian tumours and liver cirrhosis ascites. The patients with ovarian carcinoma had grades III, as well as grades I and IIc but only in cases where operative and pathological finding indicated a ruptured or perforated tumour capsule. RESULTS: The sensitivity of peritoneal cytology is 68.92%, specificity is 93.61%, positive predictive value is 89.65% and negative predictive value is 78.57%. In 30.02% of patients, the peritoneal cytology showed false negative results, while in 6.38%, the results were false positive. The highest percentage of false negative findings was 77%, found in endometrioid carcinoma. CONCLUSION: Peritoneal cytology of ascitic fluid is highly specific but has relatively low sensitivity, particularly in the case of endometrioid ovarian carcinoma. In order to increase sensitivity, peritoneal cytology should be combined with monoclonal antibodies and other biochemical and immunohistochemical markers.

The Effect of Ascorbic Acid on Mancozeb-Induced Toxicity in Rat Thymocytes.

Mancozeb, as a dithiocarbamate fungicide, has been found to exhibit toxicological manifestations in different cells, mainly by generation of free radicals which may alter antioxidant defence systems in cells. The effect of mancozeb on the cells of a primary lymphoid organ has not been studied. In the present study, the effects of mancozeb (0.2, 2 and 5 µg/ml) or mancozeb+ascorbic acid (100 µg/ml), or ascorbic acid alone or control medium alone on the levels of cell viability, apoptosis, intracellular reactive oxygen species production (ROS), mitochondrial membrane potential (MMP) and ATP levels in rat thymocytes were examined in vitro. Cells treated with mancozeb displayed a concentration-dependent increase of hypodiploid cells and ROS production followed by markedly decreased viability of the cells, MMP and ATP levels. Application of ascorbic acid significantly reduced cytotoxicity in cell cultures treated with 0.2 and 2 µg/ml of mancozeb, together with significantly decreased ROS levels and increased MMP and ATP levels. In cells treated with 5 µg/ml of mancozeb, ascorbic acid failed to reduce toxicity while simultaneously increasing the apoptosis rate of thymocytes. These results suggest that ROS plays a significant role in mancozeb-induced toxicity, through alteration of mitochondrial function. Ascorbic acid administration reduced the toxicity rate in cells treated with lower mancozeb concentrations, while it may have the ability to shift cells from necrosis to apoptosis in the presence of highest mancozeb concentrations.