Search

The cytochrome P450 superfamily consists of hemeproteins involved in the detoxication of different xenobiotics, including drugs. The CYP2 gene family is responsible for the metabolism of 80% of the drugs in clinical use. There are considerable interindividual and interethnic variabilities in the rate of drug metabolism as a result of genetic polymorphisms. The goal of our study was to determine the frequency of 10 genetic polymorphisms in CYP2 family genes to give light on the pharmacogenetic defects of the main CYPs, involved in drug metabolism, in Bulgarian individuals. We detected high allele frequency for CYP2D6*10 (0.27), CYP2D6*4 (0.22), and CYP2B6*9 (0.24), followed by CYP2C19*2 (0.14), CYP2C9*3 (0.11) and CYP2C9*2 (0.09). The genotype frequencies were also determined for all investigated variants. In total 47.2% of the analyzed individuals carried CYP2D6 genetic polymorphisms – 5.6% carried a single variant and 41.6% were found to have two or more such variants. Homozygotes for CYP2D6 variants were established among 14% of Bulgarian individuals. Determination of the prevailing pharmacogenetic polymorphisms of the CYPs, most responsible for drug metabolism, will lead to a lower risk of drug toxicity, increased drug efficacy, and drug dose optimization.

Hypoparathyroidism (hypoPT) is a relatively rare endocrine disease, mainly due to thyroid surgery. The classical supplementation with calcium and active vitamin D may represent a challenge to the clinician.

Thyroid hormones and the hypothalamic-pituitary-thyroid (HPA) axis are responsible for multiple metabolic processes and psychological well-being. Hypothyroidism can induce mood changes, depressive symptoms and even major depressive disorder. This review is focused on the pathophysiology and mechanisms through which the low level of thyroid hormones may affect the brain function, causing the characteristic symptoms of depression. Key pathways of hypothyroid-associated depressive states include: morphological changes in some brain areas (mainly in the hippocampus – a reduction in its volume); a significant reduction of the cerebral blood flow (incl. hippocampus), and lowered levels of neurotrophic factors (e. g. BDNF – brain-derived neurotrophic factor), which are regulated by the thyroid hormones. An adequate and timely thyroid hormone replacement and treatment with conventional antidepressants often can reverse the psychological symptoms.

Objective: to describe the results from intravenous calcium loads in patients with suspected PHPT.

The rising burden of depression, which will soon be the second most common cause of disability in the world, is requesting new ways to treat and prevent it. Due to high number of significant adverse drug reactions of the conventional treatment, the modern pharmaceutical industry is more often turning their focus to novel plant-based solutions. We performed literature research based on standard literature search engines – PubMed, Google Scholar, Science Direct. A standard set of keywords related to our topic e.g. “Depression”, “Mesembrine type alkaloids”, “Narcissus” was used. The review describes the classical monoamine theory of depression and connects it with the newly found biochemical, genetic and morphological alterations associated with the major depressive disorder. The purpose of this review is to highlight the most important aspects of the pathophysiology of depression and to explore the possibilities to use mesembrine-like alkaloids isolated from Narcissus cv. Hawera in its treatment. We describe their effect on brain biochemistry and possible future investigations.

Aim/objective: Corneal kindling mouse test is a model of decreasing the seizure threshold after repetitive subchronical electrical stimuli. Ketogenic diet (KD) is used for the treatment of children with pharmacoresistant epilepsy since more than 100 years. Surprisingly, very few studies testing the effect of the KD in corneal kindling test were published. The aim of this study was to evaluate the effect of the KD on the seizure activity in corneal kindling mouse model.

Data from different studies correlating the serum 25(OH)D levels with the metabolic and glycemic parameters in type 2 diabetes patients are still varying. The objective if this study was to describe the correlation between serum 25(OH)D levels and some metabolic parameters in Bulgarian type 2 diabetes patients on oral antidiabetic drugs. One hundred type 2 diabetes patients participated - 56 men and 44 women. The mean age and diabetes duration of the women was 59.0 and 9.8 years, of the men - 58.0 and 7.7 years respectively. Complete patient history was taken and physical examination was performed (body weight and height, waist circumference). Body composition was measured on a leg-to-leg body impedance analyzer (TBF-215, Tanita Corp., Tokyo, Japan). Serum levels of vitamin D were measured by electro-hemi-luminescent detection as 25-(ОН) D Total (ECLIA, Elecsys 2010, Roche Diagnostics, Switzerland). Glycated hemoglobin A1c was measured on a NycoCard reader (Alere™). Total, HDL-cholesterol (direct) and triglycerides were analyzed on a Cobas Integra 400+ analyzer. Correlation analysis was performed on a SPSS 13.0 for Windows platform and included 10 curves. The data were first analyzed for the group as a whole and then separately for men and women as well as in the different vitamin D tertiles. The mean serum 25-OH-vitamin D levels were 23.8 ± 12.1 nmol/l in women and 33.3 ± 20.0 nmol/l in men. We were unable to find any statistically significant correlation between serum 25(OH) vitaminand the serum lipids (cholesterol profile and triglycerides). On the contrary, there was a weak correlation with the glycated hemoglobin A1c (cubic model, R2 = 0.178, p = 0.05) and the BMI (inverse model, R2 = 0.101, p = 0.038). The sub-analyses (men versus women or according to tertiles of vitamin D) did not produce any additional information. The influence of vitamin D on the parameters of the metabolic control in type 2 diabetes is very weak on an individual level. It might be only demonstrated in large epidemiological surveys.

The article discusses the FAMU experiment, which investigates the proton structure. It explains that muonic atoms are used to examine the limits between theory and experiment. The article emphasizes the importance of precise measurements in studying atomic and nuclear properties. It also mentions the proton radius puzzle and the need for further research. The article concludes by mentioning different experimental proposals for measuring the proton's electromagnetic structure. Three collaborations are working on laser excitation of the muonic hydrogen atom using different approaches. The FAMU experiment uses a pulsed mid-infrared laser source and specialized detectors. The international team is working together to conduct the experiment. [Extracted from the article]

The precise measurement of transition frequencies in cold, trapped molecules has applications in fundamental physics, and extremely high accuracies are desirable. We determine suitable candidates by considering the simplest molecules with a single electron, for which the external-field shift corrections can be calculated theoretically with high precision. Our calculations show that H2+ exhibits particular transitions whose fractional systematic uncertainties may be reduced to 5 × 10-17 at room temperature. We also generalize the method of composite frequencies, introducing tailored linear combinations of individual transition frequencies that are free of the major systematic shifts, independent of the strength of the external perturbing fields. By applying this technique, the uncertainty of the composite frequency is reduced compared to what is achievable with a single transition, e.g., to the 10-18 range for HD+. Thus, these molecules are of metrological relevance for future studies. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the pharmacokinetics of tobramycin in plasma and urine in the horse ( n = 7) after intravenous administration of a dose of 4 mg/kg b.w. Plasma tobramycin concentrations were assayed microbiologically and by means of HPLC analyses. Pharmacokinetic parameters, calculated on the basis of concentrations determined with the microbiological assay were not statistically different from those obtained when data from HPLC analysis were used, but the microbiological assay was more sensitive in the detection of low plasma and urine values. The values of the total body clearance ( ClB) were 101.4 ± 30.1 and 130.0 ± 49.9 mL/kg/h, respectively. The overall extraction ratio was 2.9%. The determined capacity of elimination of tobramycin in horses was similar to those for other aminoglycosides. Within 24 h after treatment, 57.6 ± 12.2% of injected antibiotic was excreted in the urine. [ABSTRACT FROM AUTHOR]

We propose a substantial improvement of the experimental method for the measurement of the hyperfine splitting of the ground state of muonic hydrogen described in earlier papers [1,2]. By further developing the idea to use the diffusion of the muon hydrogen atoms as a signature of laser-induced hyperfine transitions, we suggest a technique based on the energy dependence of the rate of muon transfer to oxygen in the thermal region, and demonstrate its efficiency and significant practical advantages. [ABSTRACT FROM AUTHOR]

Different asymmetries in deep inelastic scattering of polarized leptons on protons that would allow to disentangle in a model independent way the effects of the weak neutral spin-0 and spin-2 bosons from that of the nonstandard spin-1 bosons are considered. The numerical estimates, obtained in the parton model are presented for the HERA facilities. The kinematical regions in which effects of nonstandard bosons with mass in the TeV-energy range might be expected are shown. [ABSTRACT FROM AUTHOR]

• Temperature dependence of the μ transfer rate from μ p to oxygen is measured. • A strong monotonic rise by a factor three of the rate is observed between 104-300 K. • This effect will be exploited to measure the hyperfine splitting of the μ p 1S state. • Experiment took place at the RIKEN muon facility, Rutherford Appleton Laboratory. • Fast scintillator counters based on LaBr3 crystals read by photomultipliers are used. We report the first measurement of the temperature dependence of muon transfer rate from muonic hydrogen atoms to oxygen between 100 and 300 K. Data were obtained from the X-ray spectra of delayed events in a gaseous target, made of a H 2 /O 2 mixture, exposed to a muon beam. This work sets constraints on theoretical models of muon transfer and is of fundamental importance for the measurement of the hyperfine splitting of muonic hydrogen ground state as proposed by the FAMU collaboration. [ABSTRACT FROM AUTHOR]

• Muon transfer rate from muonic hydrogen to oxygen measured at RIKEN RAL (UK). • Rise with the temperature of the muon transfer rate from muonic hydrogen to oxygen. • Use of LaBr 3 fast scintillator counters read by photomultiplier. • Important basis to measure the hyperfine splitting of muonic hydrogen. The first measurement of the temperature dependence of the muon transfer rate from muonic hydrogen to oxygen was performed by the FAMU collaboration in 2016. The results provide evidence that the transfer rate rises with the temperature in the range 104-300 K. This paper presents the results of the experiment done in 2018 to extend the measurements towards lower (70 K) and higher (336 K) temperatures. The 2018 results confirm the temperature dependence of Λ p O observed in 2016 and sets firm ground for comparison with the theoretical predictions. [ABSTRACT FROM AUTHOR]