Pharmacoresponsiveness of spontaneous recurrent seizures and the comorbid sleep disorder of epileptic Kcna1-null mice.

Drug resistant epilepsy affects ∼30% of people with epilepsy and is associated with epilepsy syndromes with frequent and multiple types of seizures, lesions or cytoarchitectural abnormalities, increased risk of mortality and comorbidities such as cognitive impairment and sleep disorders. A limitation of current preclinical models is that spontaneous seizures with comorbidities take time to induce and test, thus making them low-throughput. Kcna1-null mice exhibit all the characteristics of drug resistant epilepsy with spontaneous seizures and comorbidities occurring naturally; thus, we aimed to determine whether they also demonstrate pharmacoresistanct seizures and the impact of medications on their sleep disorder comorbidity.

An Evidence-Based Review of Elagolix for the Treatment of Pain Secondary to Endometriosis.

Purpose Of Review: This is a review of elagolix use for pain related to endometriosis. It summarizes the background and recent data available about the pathogenesis of endometriosis and pain that is secondary to this syndrome. It then reviews the evidence to support the use of elagolix and the indications for use.

Preoperative imaging of deep endometriosis: pitfalls of a diagnostic test before surgery.

The usefulness of a test is determined by the clinical interpretation of its sensitivity and specificity. The pitfalls of a test with a surgical endpoint are described in this article, taking the diagnosis of deep endometriosis by imaging as an example, without discussing the management of deep endometriosis. Laparoscopy is not a 100% accurate "gold standard".

A Comprehensive Review of the Diagnosis, Treatment, and Management of Urologic Chronic Pelvic Pain Syndrome.

Purpose Of Review: Urologic chronic pelvic pain syndrome (UCPPS) is a chronic, noncyclic pain condition which can lead to significant patient morbidity and disability. It is defined by pain in the pelvic region, lasting for greater than 3 to 6 months, with no readily identifiable disease process. The aim of this review is to provide a comprehensive update of diagnosis and treatment of UCPPS.

Postoperative Nausea and Vomiting in Paediatric Anaesthesia.

Postoperative nausea and vomiting (PONV) is a common complication in paediatric anaesthesia and is a source of significant morbidity. Various independent risk factors have been implicated in the development of paediatric PONV, including higher pain scores postoperatively, the use of opioids for pain management and the use of volatile anaesthetics for the maintenance of anaesthesia. This review of the current literature regarding the prevention and treatment of paediatric PONV is based on a search of the PubMed database, which identified published clinical trials, systematic reviews and meta-analyses.

Advances in the Understanding and Management of Chronic Pain in Multiple Sclerosis: a Comprehensive Review.

Purpose Of Review: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system that can lead to severe physical, cognitive, and neurological deficits that often manifest in young adults. Central neuropathic pain is a common presenting symptom, often prompting patients to seek treatment with opioids, NSAIDS, antiepileptics, and antidepressants despite minimal effectiveness and alarming side-effect profiles. Additionally, spasticity occurs in more than 80% of MS patients and is an important consideration for further study in treatment.

Minimally Invasive Interventional Management of Osteoarthritic Chronic Knee Pain.

Chronic knee pain is a widely prevalent issue that can have a significant impact on a patient's quality of life. One of the leading causes of chronic knee pain is osteoarthritis. Total knee replacement is often the last and definitive resort for patients with severe symptomatic osteoarthritis after trial of less invasive interventions with failure to achieve symptomatic relief.

[The morphological substrate and pathogenetic mechanisms of pelvic pain syndrome in endometriosis].

Objection: To study the origin and morphological substrate of pain syndrome in deep infiltrating endometriosis involving the bowel.

Subjects And Methods: The investigation was conducted using the intraoperative material (resected portions of the large and small bowels, appendix) obtained from 40 women diagnosed as having deep infiltrating endometriosis involving the bowel, which was accompanied by pain syndrome. Paraffin sections were immunohistochemically examined using the standard protocol.

[Physico-chemistry of dinitrosyl iron complexes with thiol-containing ligands underlying their beneficial treatment of endometriosis].

Exogenous dinitrosyl iron complexes (DNIC) with thiol-containing ligands as NO and NO+ donors are capable of exerting both regulatory and cytotoxic effects on diverse biological processes similarly to those characteristic of endogenous nitric oxide. Regulatory activity of DNIC (vasodilation, hypotension, trombosis suppression, red blood cell elasticity increasing, skin wound healing acceleration, penile erection inducing, etc) is determined by their capacity of NO and NO+ transfer to biological targets of the latter (hemo- and thiol-containing proteins, respectively) due to higher affinity of the proteins for NO and NO+ than that of DNIC. Cytotoxic activity of DNIC is endowed with rapid DNIC decomposition under action of iron-chelating compounds resulting in appearance of NO and NO+ in cells and tissues in high amount.

[Anticoagulant therapy in pregnant women with mechanical prosthetic heart valves. Review of international clinical guidelines].

Recently thromboembolic and hemorrhagic complications are main causes of maternal morbidity and mortality. Normal pregnancy is associated with ahypercoagulation. This condition is complicated if the patient has a mechanical prosthetic heart valve.

[Endometrial pathology in elderly and senile age (a screening study)].

The results of an annual prophylactic medical examination were studied in 288 women aged 60-87 years. Primary and repeated visits revealed that 92.9% of the patients had endometrial pathology presented with glandular-fibrous polyps that both recurred and occurred de novo.

Lysine carboxylation: unveiling a spontaneous post-translational modification.

The carboxylation of lysine residues is a post-translational modification (PTM) that plays a critical role in the catalytic mechanisms of several important enzymes. It occurs spontaneously under certain physicochemical conditions, but is difficult to detect experimentally. Its full impact is unknown.

[Dinitrosyl iron complexes with glutathione recover rats with experimental endometriosis].

The effect of binuclear dinitrosyl iron complexes (DNIC) with glutathione on endometrioid tumors in rats with experimental endometriosis has been studied. The latter was induced by an autotransplantation model, where two fragments of endometrium with myometrium (2 x 2 mm) from the left uterine horn was grafted to the inner surface of the anterior abdominal wall. The test animals received intraperitoneal injections of 0.

[Role of multislice spiral computed tomographic angiography in the treatment of uterine myoma].

The study was undertaken to enhance the diagnosis, treatment, and rehabilitation of patients with uterine myoma, by applying multislice spiral computed tomographic angiography (MSCTA) during uterine artery embolization. One hundred and twenty patients were divided into two groups: 1) 75 reproductive-age patients who underwent MSCTA before and after uterine artery embolization; 2) 45 reproductive-age patients who had previously undergone the latter according to the standard protocol. The main criteria for assessing the long-term results of treatment were patient complaints, the state of menstrual cycle and reproductive function, the sizes of the uterus and myomatous nodules, the signs of blood supply and growth of the latter, the presence or absence of new nodules.

Computational studies of membrane proteins: models and predictions for biological understanding.

We discuss recent progresses in computational studies of membrane proteins based on physical models with parameters derived from bioinformatics analysis. We describe computational identification of membrane proteins and prediction of their topology from sequence, discovery of sequence and spatial motifs, and implications of these discoveries. The detection of evolutionary signal for understanding the substitution pattern of residues in the TM segments and for sequence alignment is also discussed.

[Molecular biological features of ectopic and eutopic endometrium in genital endometriosis].

The molecular biological features of the eutopic and ectopic endometrium were studied in 46 patients with adenomyosis, 44 with endometrioid cysts in the ovaries, and 34 with disseminated mixed forms of genital endometriosis. Reproductive-aged patients with the eutopic endometrium in a proliferation phase with hyperplastic or inflammatory changes were selected. Ten samples of the endometrium in a phase proliferation, which had been obtained at medicolegal autopsy of women without reproductive disorders, were studied as a control group.

Lipid-binding surfaces of membrane proteins: evidence from evolutionary and structural analysis.

Membrane proteins function in the diverse environment of the lipid bilayer. Experimental evidence suggests that some lipid molecules bind tightly to specific sites on the membrane protein surface. These lipid molecules often act as co-factors and play important functional roles.

Structural signatures of enzyme binding pockets from order-independent surface alignment: a study of metalloendopeptidase and NAD binding proteins.

Detecting similarities between local binding surfaces can facilitate identification of enzyme binding sites and prediction of enzyme functions, and aid in our understanding of enzyme mechanisms. Constructing a template of local surface characteristics for a specific enzyme function or binding activity is a challenging task, as the size and shape of the binding surfaces of a biochemical function often vary. Here we introduce the concept of signature binding pockets, which captures information on preserved and varied atomic positions at multiresolution levels.

Cloning and characterization of a single-chain fragment of monoclonal antibody to ACE suitable for lung endothelial targeting.

Monoclonal antibody (mAb) 9B9 to angiotensin-converting enzyme (ACE) demonstrates selective accumulation in lung tissue of the rat, hamster, cat, monkey and human after systemic injection. It has also been demonstrated that mAb 9B9 is the useful tool for targeting therapeutic agents or genes to lung endothelium. In this study, we describe the generation and characterization of a single-chain derivative (scFv) of mAb9B9 (scFv 9B9).

Structural model of rho1 GABAC receptor based on evolutionary analysis: Testing of predicted protein-protein interactions involved in receptor assembly and function.

The homopentameric rho1 GABA(C) receptor is a ligand-gated ion channel with a binding pocket for gamma-aminobutyric acid (GABA) at the interfaces of N-terminal extracellular domains. We combined evolutionary analysis, structural modeling, and experimental testing to study determinants of GABA(C) receptor assembly and channel gating. We estimated the posterior probability of selection pressure at amino acid residue sites measured as omega-values and built a comparative structural model, which identified several polar residues under strong selection pressure at the subunit interfaces that may form intersubunit hydrogen bonds or salt bridges.

Detecting remote homologues using scoring matrices calculated from the estimation of amino acid substitution rates of beta-barrel membrane proteins.

Beta-barrel membrane proteins (MP) are found in Gram-negative bacteria, mitochondria and chloroplasts. They play important roles in metabolism of bacteria, where they are involved in transport of solutes in and out of the cell. Beta-barrel proteins may also act as proteases, lipases and may be important for cell-cell adhesion.

[Cytochrome P-450 aromatase expression in the ectopic and eutopic endometrium in endometriosis].

An immunoperoxidase test was used to reveal the expression of cytochrome P-450 aromatase in the eutopic and ectopic endometrium of 14 patients with ovarian endometriosis and 26 with adenomyosis, whose age ranged from 21 to 47 years (38+/-2.0 years). Five endometrial samples taken at autopsy from the women who had died from injuries at ages of 32 to 47 years and who had no uterine or ovarian abnormities served as the control.

Chapter 4. Predicting and characterizing protein functions through matching geometric and evolutionary patterns of binding surfaces.

Predicting protein functions from structures is an important and challenging task. Although proteins are often thought to be packed as tightly as solids, closer examination based on geometric computation reveals that they contain numerous voids and pockets. Most of them are of random nature, but some are binding sites providing surfaces to interact with other molecules.

[Prospects for using combined three-dimensional injection of gel transplants with autologous and allogenic cell cultures in reproductive medicine].

A combined cellular transplant for injection has been designed, by using lowly differentiated stromal fat tissue cells obtained from Wistar rats and it preserved biological and physical properties after passing through a small-diameter injection needle (an insulin syringe). A morphological study of the results of its transplantation into paraurethral tissues in 28 female rats showed that the transplant cells, autologous ones in particular, activated the proliferation of local connective tissue cell populations and retained their viability and proliferative and synthetic activities up 20 days or more. At the end of the experiment (on days 27-35), marked focal connective tissue enlargement at the site of injection of both allo- and autografts results in the narrowing of the urethral lumen.