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Biomedical subjects

Milica Prostran

Publications and source records attributed to Milica Prostran.

At least 19 recordsLinked to original sources

Single-dose intravenous simvastatin treatment attenuates renal injury in an experimental model of ischemia-reperfusion in the rat.

The effect of acute pretreatment with a single dose of simvastatin (1 mg/kg, i.v.; 30 min before ischemia) on renal dysfunction caused by ischemia-reperfusion (I/R) injury in the rat was investigated. I/R injury was induced by clamping both renal vascular pedicles for 45 min, followed by 4 h of reperfusion with saline (2 ml/kg per hour). Simvastatin significantly improved both parameters of glomerular and tubular dysfunction (e.g., creatinine levels and fractional excretion of Na(+), respectively) and especially improved the histological score, compared to control I/R-injured rats treated with saline or 10% DMSO only.

Animals↗

Homocysteine serum levels and MTHFR C677T genotype in patients with Parkinson's disease, with and without levodopa therapy.

Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N=83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients.

Adult↗

Peripheral antinociception by carbamazepine in an inflammatory mechanical hyperalgesia model in the rat: a new target for carbamazepine?

This study investigated whether carbamazepine could produce local peripheral antinociception in a rat model of inflammatory mechanical hyperalgesia, and whether adenosine receptors are involved. Carbamazepine (100-1000 nmol/paw) co-administrated with a pro-inflammatory compound, concanavalin A, into the hind paw caused a significant dose- and time-dependent anti-hyperalgesia. Coadministration of caffeine (250-1000 nmol/paw), a nonselective adenosine-receptor antagonist, as well as DPCPX (10-30 nmol/paw), a selective adenosine A(1)-receptor antagonist, with carbamazepine, significantly depressed its anti-hyperalgesic effect. Drugs injected into the contralateral hind paw did not produce significant effects. These results suggest that carbamazepine produces local peripheral anti-hyperalgesia via peripheral adenosine A(1) receptors.

Analgesics↗

Trends in consumption of psychiatric drugs in Serbia and Montenegro 2000-2004.

PURPOSE: To investigate the trends in psychiatric drugs utilization in Serbia and Montenegro over the 5-years period (2000-2004). MATERIALS AND METHODS: The wholesale data issued by the manufacturers or distributors were used. Also, the lists of drugs used from the Institute of Mental Health (institution which provides primary, secondary and tertiary psychiatric care) were used to corroborate the wholesale data. The utilization of drugs in general population was calculated using ATC/DDD methodology, and was expressed in Defined Daily Doses (DDD) per 1000 inhabitants per day. The utilization of drugs in the Institute of Mental Health was calculated from the hospital pharmacy records and was expressed as the number of DDDs per 100 bed-days. The statistics was performed using standard statistical methods. RESULTS: The general consumption of psychiatric drugs in Serbia and Montenegro significantly increased during the 2000-2004 period (from 45.1 DDD/1000 inhabitants/day in 2000 to 69.1 DDD/1000 inhour/day in 2004). The general utilization of anxiolytic/hypnotic drugs surged significantly, but the inhospital use remained rather stable. The most prominent changes were noted in the utilization of antidepressants, which doubled in that period, both in general and inhospital settings. Among antipsychotics in general population, there is a significant increase in the utilization of clozapine. In inhospital setting, there is a significant increase of total utilization of antipsychotic drugs, but this is also mainly on the account of atypicals. CONCLUSIONS: The total consumption of psychiatric drugs significantly increased. The utilization of anxiolytic/hypnotic drugs in 2004 reached 60 DDDs/1000 inhabitants/day, which is in collision with the trend in developed countries. It is necessary to form national guidelines for prescribing anxiolytic/hypnotic drugs, in order to rationalize their use. More favourable is the antidepressant (SSRIs in particular) and atypical antipsychotic drugs utilization increase.

Developing Countries↗

Type of electrical stimulation influences diaphragm response to adrenoceptor and calcium channel modulators: the role of extracellular and intracellular calcium events.

The influence of direct single pulse and subtetanic electrical stimulation (ES) on isolated rat hemidiaphragm response to adrenoceptor antagonists and calcium channel blockers was investigated. Muscle contractility was stimulated by cumulative micromolar noradrenaline. Noradrenaline effects on developed tension (Td) in the presence of various alpha- and beta-adrenoceptor antagonists (e.g., prazosin and ICI 118551) were qualitatively different during different types of ES. Also, intact L-voltage calcium channels were necessary for noradrenaline-induced potentiation of Td during both types of ES, while the balance between ryanodine receptors- and inositol triphosphate (IP3)-related calcium events in the muscle was influenced by the pattern of the ES.

Adrenergic Agents↗

Pattern of utilization of benzodiazepines in patients with hypertension: a pilot study.

BACKGROUND/AIM: The analysis of drug prescribing in general practice in Serbia showed that the use of benzodiazepines is most frequently associated with hypertension. The aim of this study was to establish the correlation of the characteristics of patients with hypertension to antihypertensive drug therapy, and the intake of benzodiazepines. METHODS: A special questionnaire was used for interviewing the patients (n = 171) chronically treated for hypertenson. Statistical tests used were chi2-test and Student's t-test. RESULTS: No differences were noted in terms of age, gender, education, body weight, smoking habits and blood pressure (155 +/- 4.9/100 +/- 2.7 mmHg vs. 160 +/- 2.2/105 +/- 3.7 mmHg), between the group I (antihypertensive drugs+benzodiazepines: n = 79), and the group II (antihypertensives only: n = 92). The patients taking benzodiazepines received a lower number of different antihypertensive drugs (2.3 +/- 0.09 vs. 2.7 +/- 0.10; p < 0.01), but the total antihypertensive drug load was significantly greater than in the group II (2.6 +/- 0.10 vs. 1.9 +/- 0.15 defined daily doses (DDD)/patient/day; p < 0.01). Benzodiazepines were taken for anxiety (62%) and hypertension (21%), rarely for insomnia, mostly once a day, at bedtime. About half the patients took benzodiazepines regularly for months or years aware of the risk for addiction. Diazepam was used by 82% of the patients. The average daily exposure to benzodiazepines was 0.45 +/- 0.05 DDD/patient/day. The drug was bought without prescription in 25% of the patients, and without consulting a physician in 12% of them. CONCLUSION: The study confirmed a close association of hypertension with the use of benzodiazepines. The frequent use of benzodiazepines in the patients with hypertension might be caused by an inadequate response to antihypertensive drug therapy, besides anxiety and insomnia. The therapeutic efficacy of a long-term use of low doses of benzodiazepines in hypertension requires further investigation.

Anti-Anxiety Agents↗

Histopathology of chronic hepatitis C in relation to virus genotype.

BACKGROUND/AIM: The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. METHODS: In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. RESULTS: In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION: The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.

Adolescent↗

Aminophylline pretreatment modulates the nitric oxide system of the isolated rat diaphragm: the role of frequency of the electrical stimulation.

The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 Hz) and aminophylline (AMPh) pretreatment on the effect of N(G)-nitro-L-arginine methyl ester (L-NAME) (1 mM) on isolated rat diaphragm was investigated. L-NAME potentiated tension developed (Td) in the diaphragm pretreated with a single concentration of AMPh (1.08 mM) in a frequency-dependent manner. The effect was significantly different in comparison with muscle incubated 30 min with Tyrode solution only. In the muscle pretreated with cumulative concentrations of AMPh (0.36 - 3.60 mM), the frequency-dependent potentiation of Td induced by L-NAME and the difference between L-NAME-treated and untreated muscle were lost.

Aminophylline↗

Treatment of anicteric acute hepatitis C with peginterferon alpha-2a plus ribavirin.

BACKGROUND: Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world. Acute hepatitis C is the most commonly asymptomatic liver disease with the development of chronic HCV infection in the majority of infected patients. Studies of the natural history of HCV infection suggest that only 15-30% of patients with acute infection recover spontaneously. Others, up to 85% of the infected patients develop chronic hepatitis C. Acute hepatitis C is so uncommon and with the unpredictable occurrence, and of the low frequency, that it is difficult to determine the optimal treatment of this disease. There have been many randomized, controlled trials of the therapy in patients with chronic hepatitis C, but none of an adequate size or rigor in patients with acute hepatitis C. Therefore, the causal treatment of patients with acute hepatitis C aimed at the prevention of chronic liver disease is necessary. CASE REPORT: We have treated a patient with anicteric form of acute hepatitis C after a three-month outpatient follow-up using a combined therapy: pegylated interferon-alpha 2a, 180 microg, subcutaneously, once a week plus ribavirin 1000 mg orally once a day. The treatment lasted 24 weeks. Stable biochemical and virological response was achieved both at the end of the treatment and 6 months after the completion of the therapy. CONCLUSION: We believe that the above mentioned might be one of the approaches to the treatment of acute hepatitis C. However, further prospective studies with significantly larger number of patients are necessary for the definite conclusions about the treatment of HCV infections.

Acute Disease↗

NG-nitro-L-arginine methyl ester-induced potentiaton of the effect of aminophylline on rat diaphragm: the role of extracellular calcium.

The role of extracellular calcium in the interaction between intracellular cAMP and nitric oxide (NO)/cGMP on the contractility of rat diaphragm pretreated with cumulative concentrations of aminophylline (0.36 - 3.60 mM) was investigated. In a Ca2+-free medium, NG-nitro-L-arginine methyl ester (L-NAME) (1 and 3 mM) depressed tension developed (Td) and also aminophylline-induced potentiation of Td in a concentration-dependent manner. Verapamil (2.5 microM) or nicardipine (20 microM) significantly antagonized the potentiating effect of L-NAME on Td in a calcium-containing medium. However, in the presence of verapamil or nicardipine, L-NAME still produced statistically significant potentiation of the cumulative concentrations of aminophylline (0.36 - 3.60 mM), given in the second series.

Aminophylline↗

NG-nitro-L-arginine methyl ester potentiates the effect of aminophylline on the isolated rat hemidiaphragm.

The effects of different concentrations of N(G)-nitro-L-arginine methyl ester (L-NAME) (0.3, 1, 3, and 10 mM), a non-selective inhibitor of NOS, on the effect of aminophylline on the isometric contraction of the isolated rat hemidiaphragm were investigated. The muscle contractions were induced by direct subtetanic electrical stimulation. Aminophylline (0.36 - 3.60 mM) produced a typical concentration-dependent increase in both parameters of the isometric contraction: tension developed (Td) and the maximum rate of rise of tension (dT/dt max). The second series of additions of aminophylline produced a more pronounced effect. L-NAME (0.3, 1, 3, and 10 mM, 30 min of incubation without stimulation) itself did not change Td and dT/dt max. However, L-NAME (1, 3, and 10 mM) produced a statistically significant potentiation of the effect of aminophylline on Td and dT/dt max.

Aminophylline↗

[Nitric oxide and lung diseases].

INTRODUCTION: All three isoforms of nitric oxide synthase (NOS) are identified within various tissues of the respiratory system. ISOFORMS OF NOS: Under physiological conditions, small amounts of NO, produced by constitutive isoforms of NOS, appear to be important in regulation of basal pulmonary vascular tone and in mediating transition from fetal to neonatal circulation; also, NO exerts antiinflammatory actions, and modulates the respiratory smooth muscle tone. NO AND RESPIRATORY TRACT DISEASES: Under pathological conditions, inducible NOS-derived NO may produce lung damage. In addition, increased or decreased production of NO is found in chronic obstructive pulmonary disease, cystic fibrosis, asthma and related inflammatory disorders, and exhaled NO level measurement is a useful tool in diagnostics of respiratory disorders. CONCLUSION: It has been shown that NO modulates contractility of the isolated diaphragm, and there are important interactions between NOS inhibitors and drugs for respiratory disorders (e.g. aminophylline).

Humans↗

[Antibiotic resistance].

INTRODUCTION: After six decades of antibiotic use, the prevalence of antibiotic-resistant bacteria is increasing, and organisms resistant to almost all antibiotics have been identified. ANTIBIOTIC RESISTANCE: It is important to understand why antibiotic resistance develops, in order to design strategies for its prevention. Factors that promote antibiotic resistance in community and hospital settings are: antibiotic selective pressure, prolonged antibiotic treatment, inadequate doses, prior use of a less effective drug of the same antibiotic class, protected sites or foreign bodies, and poor infection control practice. The best available ways to decrease and control antibiotic resistance are: rational use of antibiotics (e.g. appropriate selection of drug, dose, duration of treatment), good infection control procedures (hygienic practice and isolation), as well as local, national and global surveillance networks for monitoring dissemination of antimicrobial resistance and detection of new resistance mechanisms. CONCLUSION: Clinical guidelines, direct education, and regular reports on antibiograms may contribute to more prudent use of antibiotics. Overall, the problem of antibiotic resistance is global. However, measures need to be taken at an individual, institutional, and ultimately at national healthcare level.

Drug Resistance, Bacterial↗

[Psychiatric adverse effects induced by recombinant interferon alfa in patients with chronic hepatitis C].

INTRODUCTION: Hepatitis C virus infection is a slowly progressive chronic disease and the most common cause of chronic liver disease. Presently, interferon alfa based therapies, with or without ribavirin, are standard treatment for chronic hepatitis C virus infection. The most troublesome psychiatric side effects of interferon therapy in our patients are: insomnia, irritability, anxiety, mood changes, short temper, emotional and affective lability, impaired cognitive function, apathy, loss of motivation and the most serious depression with or without suicidal ideas. MATERIAL AND METHODS: In our study we treated 82 patients chronically infected with HCV divided into 3 groups: the first group of 31 patients (20 male and 11 female) received IFN-alfa in standard doses of 3 MU three times a week (t.i.w) during 24 weeks; the second group of 36 patients (25 male and 11 female) received IFN-alfa, 3 MU t.i.w plus ribavirin 1000-1200 mg per day during 24 weeks; the third group of 15 patients (11 male and 4 female) received IFN-alfa, 3 MU t.i.w plus ribavirin 1000-1200 mg per day during 48 weeks. The follow-up period after therapy in all groups lasted 24 weeks. RESULTS: During treatment, we observed at least one psychiatric side effect in 21 (26%) patients: insomnia in 11 (13%), emotional and affective lability in 9 (11%), anxiety, irritability and short temper in 8 (10%), impaired cognitive function in 7 (8%) apathia and loss of motivation in 6 (7%) treated patients. Depression, the most serious side effect, was established in 8 (10%) patients. All of these side effects were observed during later stages of treatment (between 5th and 22nd weeks of treatment). The incidence of all psychiatric side effects was significantly higher in women than in men (p < 0.01). We observed higher prevalence of depression among patients with history of alcohol and drug abuse. Treatment was temporarily discontinued (from 2 to 4 weeks) in all patients with depression, but it was not permanently discontinuated in any patient due to psychiatric side effects. CONCLUSION: Interferon causes psychiatric disorders that are usually mild and reversible. They disappear either spontaneously, while patients are still receiving therapy or after temporary cessation of interferon alfa therapy.

Adolescent↗

[Clinical course and prognosis in hypoxic-ischemic encephalopathy].

BACKGROUND: Establishing the value of neurological examination, and additional diagnostic methods (ultrasonography and magnetic resonance imaging of the brain) in the diagnosis and prognosis of hypoxic-ischemic encephalopathy and its treatment, tracking the clinical course, and making the prognosis of neurological development in newborn infants with hypoxic-ischemic encephalopathy. METHODS: The group of 40 term newborn infants with suspected intrauterine asphyxia was examined. All the infants were prospectively followed until the 3rd year of age at the Clinic for Neurology and Psychiatry for Children and Youth in order to estimate their neurological development and to diagnose the occurrence of persistent neurological disorders. All the infants were analyzed by their gestational age and Apgar score in the 1st and the 5th minute of life. They were all examined neurologically and by ultrasonography in the first week of life and, repeatedly, at the age of 1, 3, 6, 9, 12, 18, as well as in the 24th month of life. They were treated by the standard methods for this disease. Finally, all the infants were examined neurologically and by magnetic resonance imaging of the brain in their 3rd year of age. On the basis of neurological finding infants were divided into 3 groups: infants with normal neurological finding, infants with mild neurological symptomatology, and infants with severe neurological disorders. RESULTS: It was shown that neurological finding, ultrasonography and magnetic resonance imaging of the brain positively correlated with the later neurological development of the infants with hypoxic-ischemic encephalopathy. CONCLUSION: Only the combined use of these techniques had full diagnostic and prognostic significance, emphasizing that the integrative approach was very important in the diagnosis of brain lesions in infants.

Child Development↗