High prevalence of therapy-resistant epilepsy demands development of anticonvulsants with new mechanisms of action. Brivaracetam is an analogue of levetiracetam which binds to the synaptic vesicle protein 2A (SV2A) and decreases release of excitatory neurotransmitters. Areas covered: Relevant published studies were searched for by predefined strategy in MEDLINE, EBSCO and SCINDEKS electronic databases. Brivaracetam is effective as adjunctive therapy for uncontrolled partial-onset seizures with or without secondary generalization in patients 16 years and older with epilepsy. It reduces baseline-adjusted focal seizure frequency per week from 7.3 to 12.8% over placebo. Adverse events rate in patients with brivaracetam is not higher than in patients with placebo. Expert opinion: Brivaracetam is an important step forward in the treatment of therapy-resistant partial-onset seizures with or without secondary generalization. Its development was systematic and targeted. Due to its efficacy and excellent safety profile, it is likely that brivaracetam will be often prescribed. In future, efficacy and safety of brivaracetam should be tested in monotherapy settings and also in the first-line therapy of partial-onset seizures.
Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage‐dependent channels for Na+, K+ and Ca2+, but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10−9 M/L to 1.4 × 10−6 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10−8 M/L, r = 0.580, P < 0.05) (F = 2.980, df1 = 6, df2 = 28, P < 0.05). Paroxetine (from 1.2 × 10−9 M/L to 5.1 × 10−5 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10−8 M/L, r = 0.500, P < 0.05) (F = 2.350, df1 = 9, df2 = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.
Granulosa cell tumor is a type of neoplasm, which represents 2-5% of all ovarian cancers. About 5% of these tumors are juvenile- type and usually occur to girls before puberty and to women younger than thirty years of age. There are signs premature puberty or premature emergence of secondary sexual characteristics with irregular vaginal bleeding that occur to these kind of patients. To the rare cases, like this, the occurrence of granulosa cell tumors can cause the appearance of hyperandrogenism with high levels of plasma testosterone, leading to virilization which happened to this female patient. We will present the female patient who was 35 years old and which was originally hospitalized to the Clinic for Haematology Clinical Center Kragujevac, because of extreme fatigue accompanied by dizziness. During diagnostics the patient underwent to the complete gynecological examination. After gynecological examinations and necessary diagnostic procedures, it was decided continuing the treatment at the Clinic of Gynecology and Obstetrics Clinical Center Kragujevac, where she underwent a total abdominal hysterectomy with bilateral salpingo- oophorectomy for suspected uterine neoplasm. Histopathological analysis of the obtained material confirmed the presence of follicular cysts of both ovaries and juvenile type granulosa cell tumor on the right ovary; the uterus was enlarged with multiple fibroid tumors. Granulosa cell tumor should be suspected in the cases of girls and young females if there is present an ovarian cyst paired with signs of preterm puberty or hyperestrogenism. In this case, the presence of granulosa cell tumor was masked by signs of hyperandrogenism, which is not so typical, as well as the presence of uterine fibroids who have actually been the main cause for surgical treatment.
To establish the role of co-overexpression of bcl-2 and c-myc protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL), high grade SIL, portio vaginalis uteri (PVU) carcinoma in situ and PVU invasive carcinoma, stage IA-IIA (study group) and 36 samples without SIL or malignancy (control group). The expression of bcl-2 and c-myc was detected immunohistochemically using a monoclonal antibody. Fisher's exact test (P<0.05) was used to assess statistical significance. Overexpression of bcl-2 was found to increase in direct relation to the grade of the cervical lesions. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be said that in patients with bcl-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. Co-overexpression of bcl-2 and c-myc oncogenes was found only in patients with PVU invasive carcinoma (6/26-23.0%). Statistically significant difference was not found in the frequency of co-overexpression in patients with PVU invasive carcinoma in relation to the control group (Fisher's test; P=0.064). The method's sensitivity of determining these oncogenes with the aim of detecting PVU invasive carcinoma was 23%, while specificity was 72.2%. On the basis of high predictive values (100%), speaking in statistical terms, it can be concluded that all patients with co-overexpression of bcl-2 and c-myc oncogenes will have PVU invasive carcinoma. We confirmed in our research that co-overexpression of bcl-2 and c-myc oncogenes was increased only in PVU invasive carcinoma. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of bcl-2 and c-myc co-overexpression in cervical carcinogenesis.
Introduction. Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive multisystem disorder associated with biallelic mutations of the SMARCAL1 gene. Vascular central nervous system complications in the form of Moyamoya syndrome (MMS) have been reported as a comorbidity in nearly half of the cases clinically presenting with severe migraine-like headaches, transient ischemic attacks (TIA) and ischaemic or haemorrhagic infarctions. We present an illustrative case of infantile form of SIOD with MMS, with a review of the latest diagnostic possibilities, as well as current diagnostic and therapeutic dilemmas in managing SIOD. Case report. We report the case of a female patient with the infantile form of SIOD. The proband was born small for gestational age in the 34th gestation week with characteristic dysmorphic features. Genetic testing found a biallelic, nonsense mutation c.2542G>T in the SMARCAL1 gene. She presented early with TIA, seizures and recurrent ischemic strokes. Magnetic resonance imaging (MRI) confirmed the presence of progressive brain atrophy with bilateral occlusion/stenosis of middle (MCA) and anterior (ACA) cerebral arteries and a smoke like collateral vessel appearance consistent with a Moyamoya syndrome. Conclusion. Patients with SIOD may present with progressive cerebral vascular changes and clinical neurologic deterioration early in the course of disease. In such patients early diagnosis and preventive revascularization surgery are of paramount importance. In diagnosing Moyamoya syndrome MRI angiography can be an appropriate substitute for a standard invasive cerebral angiography.
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