Vaginismus - who takes interest in it?

OBJECTIVE: Vaginismus is caused by involuntary spasm of muscle surrounding the vaginal wall, a condition which makes it impossible to have a comfortable sexual intercourse. Due to its significant psychogenic part this topic is often neglected by specialists, however it is a very sensitive one for women patients. We are bringing a summary of literature dealing with vaginismus, clarifying the possibilities of diagnostics, therapy and we are discussing relation of this dysfuntion to reproduction. DESIGN: Review article. Material a methods: Recent scientific articles indexed in Pubmed, Medline, Web of Science, consultation of Czech specialists and discussion forums of patients have been used. RESULTS: Vaginismus influences the quality of life, in the most serious form in can result in unconsumated marriage, sterility and thus can lead to the separation of a couple. When adeaquately approached the problem can mostly be solved. CONCLUSIONS: There are women for whom vaginismus is a serious problem and who are not able to cope with the situation without specialists help. Deepening the specialists knowledge in this field is essential for successful treatment.

SPR biosensor for quantification of fetuin-A as a promising multibiomarker.

Early diagnosis of ongoing malignant disease is crucial to improve survival rate and life quality of the patients and requires sensitive detection of specific biomarkers e.g. prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), etc. In spite of current technological advances, malignant diseases are still identified in rather late stages, which have detrimental effect on the prognosis and treatment of the disease. Here, we present a biosensor able to detect fetuin-A, a potential multibiomarker. The biosensing platform is based on polymer brush combining antifouling monomer units of N-(2-hydroxypropyl)methacrylamide (HPMA) and carboxybetaine methacrylamide (CBMAA), statistically copolymerized by surfaceinitiated atom transfer radical polymerization. The copolymer poly(HPMA-co-CBMAA) exhibits excellent non-fouling properties in the most relevant biological media (i.e. blood plasma) as well as antithrombogenic surface properties by preventing the adhesion of blood components (i.e. leukocytes; platelets; and erythrocytes). Moreover, the polymer brush can be easily functionalized with biorecognition elements maintaining high resistance to blood fouling and the binding capacity can be regulated by tuning the ratio between CBMAA and HPMA units. The superior antifouling properties of the copolymer even after biofunctionalization were exploited to fabricate a new plasmonic biosensor for the analysis of fetuin-A in real clinical blood plasma samples. The assay used in this work can be explored as labelfree affinity biosensor for diagnostics of different biomarkers in real clinical plasma samples and to shift the early biomarker detection toward novel biosensor technologies allowing point of care analysis.

[Milk Thistle (Silybum Marianum) as a Supportive Phytotherapeutic Agent in Oncology]. / Ostropestrec mariánský (Silybum marianum) jako podpurný fytoterapeutický prostredek v onkologii.

BACKGROUND: Milk thistle (Silybum marianum) has been traditionally used in medicine, particularly in the treatment of liver diseases. Today, it is used for the same purpose in evidence-based medicine (EBM). Its main active ingredient is a complex of flavonolignans, known as silymarin. Silymarin is used as a hepatoprotective agent, but its potential therapeutic use in oncology patients has drawn attention only recently. PURPOSE: The aim of this review is to provide comprehensive information on the potential therapeutic effects of milk thistle in oncology patients and potential indications for its use as a supportive therapy either as an anticarcinogenic agent or as an agent that attenuates the side effects of oncological treatments. Evidence of its effects and its safety, and possible interactions with other cancer treatments are emphasized. Available findings are supported mainly by in vitro studies and the results of animal research, but the number of clinical trials in oncology patients is increasing. Based on the results of these studies, milk thistle or silymarin could be beneficial in oncology patients, especially for the treatment of the side effects of anticancer chemotherapeutics. Evidence from clinical studies shows that it has mainly beneficial effects in hepatotoxicity and radiotherapy-induced skin and mucosa damage at dosages of 160-600 mg daily.Key words: phytotherapy - drug-herb interactions - cancer - adverse effects - milk thistle - Silybum marianum This publication was written at Masaryk University as part of the project "Experimental and translational pharmacological research and development", number MUNI/A/1063/2016 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2017. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 6. 2017Accepted: 18. 9. 2017.

Olfactory bulbectomy in methamphetamine-treated rat mothers induces impairment in somatic and functional development of their offspring.

Olfactory bulbectomy in rodents is considered a putative model of depression. Depression is often associated with drug addiction. Our previous studies demonstrated that methamphetamine (MA) administration to rat mothers affects both, mothers and their pups. The aim of the present study was to examine the effect of bulbectomy, as a model of depression, and MA administration on behavior of rat mothers and postnatal development of their pups. Adult female Wistar rats were randomly divided into two groups: bulbectomized (OBX) and sham-operated (SH). A period of 20 days was allowed for the development of the depressive-like phenotype. Animals were tested in the motor activity test and 2 % sucrose preference for anhedonia and hyperactive locomotor response to a novel environment, respectively. After then females were impregnated. Pregnant females were exposed to daily subcutaneous (s.c.) injection of MA (5 mg/kg) or saline (SA) during the entire gestation period. Postnatally, maternal behavior and pup development was examined. The effect of a challenge dose of MA (1 mg/kg, s.c.) on behavior was further examined in adult male offspring. Our results showed no differences in the maternal behavior as a matter of bulbectomy, only OBX rats slept more than all the SH controls. Pups from OBX mothers were born with lower birthweight and gained less weight during the postnatal development than pups from SH controls. Both, bulbectomy and MA administration, delayed the eyes opening. As a matter of functional development of the pups, maternal OBX procedure impaired the performance in the Bar-holding test, but only in saline group. OBX/SA group was the worst in the Bar-holding test relative to all the other groups. In addition, pups from OBX mothers dropped more boluses during the Bar-holding test, suggesting that they were more stressed. In adult male offspring, bulbectomy increased immobility only in the SA/SA group. Prenatal MA exposure increased locomotion, while decreasing immobility. In addition, challenge dose of MA in adulthood increased distance traveled, locomotion, rearing, and average and maximal velocity, while decreasing immobility and grooming. In conclusion, our results suggest that depressive-like phenotype of rat mothers induces impairment in somatic and functional development of their male offspring.

[Curcumine (Turmeric - Curcuma longa) as a Supportive Phytotherapeutic Treatment in Oncology]. / Kurkumin (Kurkumovník dlouhý - Curcuma longa) jako podpurný fytoterapeutický prostredek v onkologii.

BACKGROUND: Turmeric (Curcuma longa) is mainly known as a constituent of curry spice. The main active ingredient, responsible for most of its biological effects, is the polyphenol curcumin. AIM: This review aims to provide a comprehensive overview of studies evaluating the benefits of therapeutic curcumin use in oncology. Preclinical studies provide information on the mechanism of action and potential toxicity of curcumin. Clinical studies have so far focused mainly on safety, pharmacokinetics, and determination of the optimal dose of curcumin. However, there are a growing number of trials evaluating the anti-tumor and oncopreventive effects of curcumin and its effect in alleviating the adverse effects of chemotherapeutics and radiotherapy. So far, the results have been optimistic and should encourage further research. The main problem associated with curcumin treatment is its low oral bioavailability, which means it must administrated at high doses to be effective. Therefore, curcumin is more appropriate as a local treatment for areas such as the intestine, mucous membrane, or the skin, where there is no need for a strong systemic effect. Curcumin has a good safety profile when used up to several grams. Curcumin can also be used as a food supplement for people at increased risk of oncological disease, such as heavy smokers or those with pre-cancerous lesions. Due to its good safety profile, curcumin can be recommended to oncological patients who request a natural treatment.Key words: phytotherapy - drug-herb interactions - cancer - adverse effects - curcumine - turmeric - Curcuma longaSubmitted: 20. 7. 2017Accepted: 25. 9. 2017 This publication was written at Masaryk University as part of the project "Behavioural psychopharmacology and pharmacokinetics in preclinical drug research", number MUNI/A/1132/2017 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2018. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

A Novel Mutation in the FECH Gene in a Czech Family with Erythropoietic Protoporphyria and a Population Study of IVS3-48C Variant Contributing to the Disease.

Erythropoietic protoporphyria (EPP), a chronic erythropoietic porphyria, is characterized by excess accumulation of protoporphyrin, particularly in erythroid cells. EPP inheritance is complex, almost always associated with two molecular defects. In most EPP patients, clinical expression requires coinheritance of a private ferrochelatase (FECH) mutation trans- to a hypomorphic FECH*IVS3-48C allele. This leads to a decrease of FECH activity below the critical threshold. This is characterized by cutaneous photosensitivity in early childhood such as itching, burning, swelling and redness in sun-exposed areas. Hepatic failure occurs in some patients (about 1-10 % of EPP patients), which may necessitate liver transplantation. We investigated a Czech family with two patients with manifested EPP in four generations. We found a novel mutation, c.84G >A, in the FECH gene in four individuals including proband and his mother (G84A transition in exon 2; p.W28*). Both clinically manifested probands inherited the hypomorphic IVS3-48C allele as well, while two clinically latent individuals with FECH mutation did not. To address the question whether the relatively low incidence of EPP in the Czech Republic might be due to lower frequency of the IVS3-48C allele, we screened for the frequency of the low expression allele in a control Czech (West Slaves) Caucasian population. Such study has not been performed in any Slavic population. Among 312 control individuals, there were no IVS3-48C/C (c.68-23C-T) homozygotes; 35 IVS3-48C/T heterozygous individuals were detected. The frequency of IVS3-48C allele was thus found to be 5.5 % in the Czech population, comparable to most West Caucasian populations.

Multitrait quantitative trait Loci mapping for milk production traits in danish Holstein cattle.

The aims of this study were (1) to confirm previously identified quantitative trait loci (QTL) on bovine chromosomes 6, 11, 14, and 23 in the Danish Holstein cattle population, (2) to assess the pleiotropic nature of each QTL on milk production traits by building multitrait and multi-QTL models, and (3) to include pedigree information on nongenotyped individuals to improve the estimation of genetic parameters underlying the random QTL model. Nineteen grandsire families were analyzed by single-trait (ST) and multitrait (MT) QTL mapping methods. The variance component-based QTL mapping model was implemented via restricted maximum likelihood (REML) to estimate QTL position and parameters. Segregation of the previously identified QTL was confirmed on bovine chromosomes 6, 11, and 14, but not on 23. A highly significant (1% chromosome-wise level) QTL was found on chromosome 6, between 37 and 73 cM. This QTL had a strong effect on protein percentage (PP) and fat percentage (FP) according to ST analyses, and effects on PP, FP, milk yield (MY), fat yield (FY), and protein yield (PY) in MT analyses. A QTL affecting PP was detected on chromosome 11 (at 70 cM) using ST analysis. The MT analysis revealed a second QTL (at 67 cM) approaching significance with an effect on MY. The ST analysis identified a QTL for MY and FP on chromosome 14, between 10 and 24 cM. The extended pedigree (nongenotyped animals) was included to estimate genetic parameters underlying the random QTL model; that is, additive polygenic and QTL variances. In general, the estimates of the QTL variance components were smaller but more precise when the extended pedigree was considered in the analysis.

Cell swelling induced secretion of TRH by posterior pituitary, hypothalamic paraventricular nucleus and pancreatic islets: effect of L-canavanine.

The aims of this study were to test if ethanol induces thyrotropin-releasing hormone (TRH) secretion in vitro from the posterior pituitary and hypothalamic explants by a mechanism involving cell swelling, and to characterize the pathway of stimulated secretion. Ethanol, at a concentration of 80 mM, stimulated the release of TRH from the posterior pituitary, the hypothalamic paraventricular nucleus, the median eminence, and the brain septum, when administered only in isosmolar but not in hyperosmolar medium. This indicates the involvement of a cell swelling-inducing mechanism. L-canavanine in a concentration of 3 mM, increased the basal and hyposmosis-induced TRH secretion from the posterior pituitary and the paraventricular nucleus, and both basal and ethanol-induced TRH secretion from isolated pancreatic islets. This indicates the presence of both constitutive and regulatory secretory pathways. Our results suggest that cell swelling induces exocytosis from clathrin coated granules.

[Penetration of cervical mucus by native and cryopreserved sperm--the Kremer test]. / Penetrace nativních a kryokonzervovaných spermií ovulacním hlenem--Kremeruv test.

OBJECTIVE: The penetration of native and cryopreserved human spermatozoa into cervical mucus--the Kremer's test. DESIGN: Retrospective study. SETTING: Department of Obstetrics and Gynaecology, Medical Faculty, Charles University and Faculty Hospital, Plzen. METHODS: Human cervical mucus was collected from 73 women visiting the Division of immunology of reproduction, Department of Obstetrics and Gynaecology in Plzen. Native spermatozoa was obtained from the patients of the Division of Immunology of Reproduction as well. Cryopreserved only in its seminal plasma was obtained from the spermabank of our department. The distance of penetration in centimetres from the start was examined in inverse microscopy after 30, 60, 90 and 90 minutes. Also the character and duration of the sperm motility was analyzed. RESULTS: The penetration of native spermatozoa was higher than the penetration of cryopreserved spermatozoa in each case. The native spermatozoa had a higher penetrability, motility and life-ability. Spermatozoa preserved only in its seminal plasma had the parameters demonstrably lower. Nevertheless these spermatozoa can be successfully used for homologue or heterologue insemination or for IVF because these spermatozoa do not loose its enzymatic and remaining energetic equipment by penetration the cervical canal. CONCLUSION: The Kremer's test belongs to the reliable methods of penetration ability of native and cryopreserved sperms.

The osmotic component of ethanol and urea action is critical for their immediate stimulation of thyrotropin-releasing hormone (TRH) release from rat brain septum.

There is considerable evidence linking alcohol consumption and sedation and TRH in the brain septum. Moreover, innate septal TRH concentration is inversely related to the degree of ethanol preference. Recently we demonstrated in rats that four-week ethanol drinking increased the septal TRH content by 50 %. We had shown previously that ethanol induces neuronal swelling, which is known to evoke the secretion of hormones, peptides and amino acids from various types of cells. We have therefore explored the effect of hyposmotic medium and of 80 and 160 mM ethanol and 80 mM urea (both permeant molecules) in isosmotic and hyperosmotic (preventing cell swelling) media on the in vitro release of TRH by the rat septum. Lowering medium osmolarity resulted in a hyposmolarity-related increase in TRH secretion. Both ethanol and urea stimulated TRH release only in isosmolar solution. Our data indicate that ethanol in clinically relevant concentrations can induce TRH release from the septum by a mechanism involving neuronal swelling.