Herbal extracts modulate the amplitude and frequency of slow waves in circular smooth muscle of mouse small intestine

Background: Herbal preparations like STW 5 (Iberogast(R)) are widely used drugs in the treatment of dyspepsia and motility-related disorders of the gastrointestinal tract. STW 5 is a phytotherapeutic agent consisting of a fixed mixture of 9 individual plant extracts. The electrophysiological mechanisms of action of STW 5 remain obscure. Aim: The aim of the present study was to investigate whether herbal extracts influence electrophysiological parameters of the small intestine. For this purpose, the resting membrane potential (RMP) and the slow wave rhythmicity of smooth muscle cells of mouse small intestine were observed. Methods: Intracellular recordings of smooth muscle cells of the circular muscle layer of mouse small intestine were performed using standard microelectrode techniques. After dissection of the mucosa, the small intestine was placed in an organ bath and a microelectrode was applied on a circular smooth muscle cell. The RMP and the amplitude of slow waves were measured in millivolts. Results: The RMP of smooth muscle cells was - 59 +/- 1.3 mV. This RMP was significantly depolarized by STW 5 ( 9.6 +/- 1.6 mV); the depolarizing effects can be mainly attributed to the constituents of matricariae flos, angelicae radix and chelidonii herba. The basal frequency of small intestinal slow waves was 39.5 +/- 1.4 min(-1) and the amplitude was 23.1 +/- 0.9 mV. STW 5 significantly reduced the amplitude and frequency of the slow waves ( 11.7 +/- 0.8 mV; 33.5 +/- 3.4 min(-1)). This effect on slow waves represents the sum of the effects of the 9 phytoextracts. Whereas angelicae radix and matricariae flos completely blocked slow wave activity, Iberis amara increased the frequency and amplitude, chelidonii herba reduced the frequency and amplitude of the slow waves, mentae piperitae folium reduced the frequency and left amplitude unchanged and liquiritae radix, carvi fructus and melissae folium had no effects. Conclusion: Herbal extracts cause changes in smooth muscle RMP and slow wave rhythmicity, up to reversible abolition, by blockade of large conductance Ca2+ channels and other not yet identified mechanisms. In herbal preparations like STW 5 these effects add up to a total effect and this study indicates that herbal preparations which are widely used in dyspepsia and motility-related disorders have characteristic, reproducible, reversible effects on small intestinal electrophysiology. Copyright (C) 2005 S. Karger AG, Basel

Quadratic Corrections to Harmonic Vibrational Frequencies Outperform Linear Models

Simulating accurate infrared spectra is a longstanding problem in computational quantum chemistry. Linearly scaling harmonic frequencies to better match experimental data is a popular way of approximating anharmonic effects while simultaneously attempting to account for deficiencies in ab initio method and/or basis set. As this approach is empirical, it is also non-variational and unbounded, so it is important to separate and quantify errors as robustly as possible. Eliminating the confounding factor of methodological incompleteness enables us to explore the intrinsic accuracy of the scaling approach alone. We find that single-coefficient linear scaling methods systematically overcorrect low frequencies, while generally undercorrecting higher frequencies. A two-parameter polynomial model gives significantly better predictions without systematic bias in any spectral region, while a single-parameter quadratic scaling model is parameterized to minimize overcorrection errors while only slightly decreasing predictive power

Molecular second-quantized Hamiltonian:Electron correlation and non-adiabatic coupling treated on an equal footing

We introduce a new theoretical and computational framework for treating molecular quantum mechanics without the Born–Oppenheimer approximation. The molecular wavefunction is represented in a tensor-product space of electronic and vibrational basis functions, with electronic basis chosen to reproduce the mean-field electronic structure at all geometries. We show how to transform the Hamiltonian to a fully second-quantized form with creation/annihilation operators for electronic and vibrational quantum particles, paving the way for polynomial-scaling approximations to the tensor-product space formalism. In addition, we make a proof-of-principle application of the new Ansatz to the vibronic spectrum of C2

ДВУХЭТАПНЫЙ РЕОСТЕОСИНТЕЗ У ПАЦИЕНТА С ЛОЖНЫМ СУСТАВОМ БОЛЬШЕБЕРЦОВОЙ КОСТИ, ОСЛОЖНЕННЫМ ХРОНИЧЕСКИМ ПОСЛЕОПЕРАЦИОННЫМ ОСТЕОМИЕЛИТОМ

The authors present a case report of a patient with pseudarthrosis of the right tibia complicated by chronic postoperative osteomyelitis. The development of the osteomyelitis process is caused by locked intramedullary fixation of the right tibia by a retrograde nail. Unstable fixation led to the development of acute periimplant infection and osteomyelitis.A radical surgical debridement of the focus site of chronic infection was performed by removing locking screws and nail, removal of necrotic bone tissues by handling the tibial medullary cavity by special reamers. The authors used the pulse lavage with active removal of the solution for an additional sterilization of the surgical wound and medullary cavity. A reinforced spacer impregnated with vancomycin and polyvalent bacteriophage was placed in the medullary cavity to ensure local prolonged antimicrobial therapy. Instead of the removed monomer the polyvalent bacteriophage was introduced into the polymer composition including phages against the main infectious agents in patients of traumatology and orthopedics clinic.Three months after the first stage of treatment and stabilization of laboratory parameters the patient was readmitted to the clinic. The second stage of procedure included removal of spacer, closed antegrade locked internal fixation of the right tibia and talus by a nail with an antimicrobial coating of bone cement impregnated with vancomycin and a polyvalent bacteriophage. Antimicrobial coating of the nail was made intraoperatively using an original mold.Two stage procedure allowed to achieve a stable remission of chronic osteomyelitis and stable internal fixation of tibia pseudarthrosis with preservation of the supporting function of the lower limb.Представлено клиническое наблюдение пациента с ложным суставом костей правой голени, осложненным хроническим послеоперационным остеомиелитом. Развитие остеомиелитического процесса было обусловлено блокируемым интрамедуллярным остеосинтезом костей правой стопы и правой голени ретроградным штифтом. Нестабильный остеосинтез привел к развитию острой периимплантой инфекции и остеомиелита. Пациенту выполнена радикальная хирургическая санация очага хронической инфекции путем удаления блокирующих винтов и штифта, обработка костномозгового канала большеберцовой кости специальными риммерами. С целью дополнительной стерилизации операционной раны выполнена обработка раны и костномозгового канала большеберцовой кости системой пульс-лаваж с активным вакуумированием раствора. Для проведения локальной пролонгированной антимикробной терапии в медуллярный канал большеберцовой кости имплантирован армированный интрамедуллярный антимикробный спейсер, импрегнированный ванкомицином и поливалентным бактериофагом.Спустя три месяца после первого этапа лечения и стабилизации лабораторных пациент был госпитализирован повторно. Проведен второй этап лечения — удаление спейсера, закрытый антеградный блокируемый остеосинтез правой большеберцовой и таранной костей штифтом с антимикробным покрытием из костного цемента, импрегнированного ванкомицином и поливалентным бактериофагом. В результате проведенного этапного лечения остеомиелит купирован, достигнута стабильная внутренняя фиксация ложного сустава большеберцовой кости с сохранением опорной функции конечности.Предложенный метод лечения является альтернативой внеочаговому компрессионнно-дистракционному остеосинтезу по методу Илизарова при лечении пациентов с периимплантной инфекцией после интрамедуллярного остеосинтеза длинных трубчатых костей

How accurately can perturbative and variational vibrational models predict the fundamental frequencies of dihalomethanes?

Three dihalogenated methane derivatives (CH2F2, CH2FCl, and CH2Cl2) were used as model systems to compare and assess the accuracy of two different approaches for predicting observed fundamental frequencies: canonical operator Van Vleck vibrational perturbation theory (CVPT) and vibrational configuration interaction (VCI). For convenience and consistency, both methods employ the Watson Hamiltonian in rectilinear normal coordinates, expanding the potential energy surface (PES) as a Taylor series about equilibrium and constructing the wavefunction from a harmonic oscillator product basis. At the highest levels of theory considered here, fourth-order CVPT and VCI in a harmonic oscillator basis with up to 10 quanta of vibrational excitation in conjunction with a 4-mode representation sextic force field (SFF-4MR) computed at MP2/cc-pVTZ with replacement CCSD(T)/aug-cc-pVQZ harmonic force constants, the agreement between computed fundamentals is closer to 0.3 cm-1 on average, with a maximum difference of 1.7 cm-1. The major remaining accuracy-limiting factors are the accuracy of the underlying electronic structure model, followed by the incompleteness of the PES expansion. Nonetheless, computed and experimental fundamentals agree to within 5 cm-1, with an average difference of 2 cm-1, confirming the utility and accuracy of both theoretical models. One exception to this rule is the formally IR-inactive but weakly allowed through Coriolis-coupling H-C-H out-of-plane twisting mode of dichloromethane, whose spectrum we therefore revisit and reassign. We also investigate convergence with respect to order of CVPT, VCI excitation level, and order of PES expansion, concluding that premature truncation substantially decreases accuracy, although VCI(6)/SFF-4MR results are still of acceptable accuracy, and some error cancellation is observed with CVPT2 using a quartic force field

Topical and Systemic Cannabidiol Improves Trinitrobenzene Sulfonic Acid Colitis in Mice

Background/Aims: Compounds of Cannabis sativa are known to exert anti-inflammatory properties, some of them without inducing psychotropic side effects. Cannabidiol (CBD) is such a side effect-free phytocannabinoid that improves chemically induced colitis in rodents when given intraperitoneally. Here, we tested the possibility whether rectal and oral application of CBD would also ameliorate colonic inflammation, as these routes of application may represent a more appropriate way for delivering drugs in human colitis. Methods: Colitis was induced in CD1 mice by trinitrobenzene sulfonic acid. Individual groups were either treated with CBD intraperitoneally (10 mg/kg), orally (20 mg/kg) or intrarectally (20 mg/kg). Colitis was evaluated by macroscopic scoring, histopathology and the myeloperoxidase (MPO) assay. Results: Intraperitoneal treatment of mice with CBD led to improvement of colonic inflammation. Intrarectal treatment with CBD also led to a significant improvement of disease parameters and to a decrease in MPO activity while oral treatment, using the same dose as per rectum, had no ameliorating effect on colitis. Conclusion: The data of this study indicate that in addition to intraperitoneal application, intrarectal delivery of cannabinoids may represent a useful therapeutic administration route for the treatment of colonic inflammation. Copyright (C) 2012 S. Karger AG, Base

Acute Adhesive Small Bowel Obstruction: a Comparative Analysis of Open and Laparoscopic Surgery

Background. Acute adhesive small bowel obstruction (AASBO) is a common surgical emergency requiring immediate interventions. AASBO is a usual indication for both small bowel resection and adhesiolysis. Postoperative adhesions cause 60% of small bowel obstructions.Materials and methods. An analysis of treatment outcomes is presented for 197 acute adhesive small bowel obstruction patients; 63 patients had urgent laparotomy, and 134 were scheduled for laparoscopy. The examination included physical, laboratory, radiological methods (abdominal radiography, ultrasound, CT scan), laparoscopy and intra-abdominal pressure monitoring.Results and discussion. Of 134 patients scheduled for laparoscopic adhesiolysis, only 46.2% had laparoscopy completed, and 53.8% required conversion to laparotomy. The main rationale for conversion were massive adhesions, intraoperative haemodynamic instability, a need for intestinal decompression, as well as rare complications. Laparoscopic operations were reported with the lower vs. laparotomy rates of surgical complications (6.4  vs. 12.69%), mortality (6  vs. 6.3%), shorter hospital stays (6.5 vs. 12 days) and operation times (75 vs. 118 min, respectively).Conclusion. Laparoscopic surgery in acute adhesive small bowel obstruction was feasible in 31.47% patients and in 46.2% — after a diagnostic laparoscopy; however, a thorough patients selection for laparoscopic adhesiolysis is necessary. The first estimated should be the patient’s haemodynamic stability, the severities of condition, adhesions and comorbid cardiorespiratory pathology. Grade I—II adhesions are an indication for laparoscopic surgery

Острый аппендицит: как часто выполняется «напрасная» аппендэктомия?

   Introduction. At present, medical practice lacks a unifi ed approach to the choice of therapeutic tactics for acute catarrhal appendicitis and therefore lacks understanding of negative appendectomy.   Aim. To study the incidence of negative appendectomy in acute appendicitis. Materials and methods. The methodology involved a retrospective analysis of the results of 1590 appendectomies performed from 2003 to 2005 and a prospective non-randomized study of 1112 patientsfor the period from 2018 to 2019. During the first observation period, the examination included physical and laboratory examinations, and in the second period, Alvaro scoring, ultrasound scan, and videolaparoscopy.   Results and discussion. In the first period, catarrhal forms of appendicitis were reported in 7.82 % of cases, while in the second period — in 3.04 %. The diagnoses were confi rmed pathohistologically in all cases.   Conclusion. No cases of performing negative appendectomy were reported, based on the results of clinical, endoscopic and pathomorphological examinations. However, the ambiguous interpretation of acute catarrhal appendicitis in the national clinical practice guidelines for acute appendicitis does not allow for unambiguous conclusions from the study.   Введение. На сегодня не существует общепринятого подхода в выборе лечебной тактики при остром катаральном аппендиците и, соответственно, понимания так называемой «напрасной» аппендэктомии.   Цель работы. Изучить частоту выполнения т. н. «напрасных» аппендэктомий при остром аппендиците.   Материалы и методы. Проведен ретроспективный анализ результатов 1590 аппендэктомий за 2003–2005 гг. и проспективное нерандомизированное исследование 1112 пациентов за 2018–2019 гг. За первый период наблюдения обследование включало физикальное, лабораторное исследования, во II период обследование по шкале Alvarado, УЗИ, видеолапароскопию.   Результаты и обсуждение. В первый период катаральные формы аппендицита были в 7,82 %, во II — 3,04 %, патогистологически во всех случаях диагнозы были подтверждены.   Заключение. Случаев выполнения «напрасных» аппендэктомий по результатам клинического, эндоскопического и патоморфологического исследований не выявлено, однако неоднозначная трактовка острого катарального аппендицита в национальных клинических рекомендациях по острому аппендициту не позволяет делать однозначные выводы из исследования

The Molpro quantum chemistry package

Molpro is a general purpose quantum chemistry software package with a long development history. It was originally focused on accurate wavefunction calculations for small molecules but now has many additional distinctive capabilities that include, inter alia, local correlation approximations combined with explicit correlation, highly efficient implementations of single-reference correlation methods, robust and efficient multireference methods for large molecules, projection embedding, and anharmonic vibrational spectra. In addition to conventional input-file specification of calculations, Molpro calculations can now be specified and analyzed via a new graphical user interface and through a Python framework

Endocannabinoids-related compounds in gastrointestinal diseases

The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases