Molecular pharmacology

This work is concerned with the role of evolutionary conserved substances, neurotransmitters, and neurohormones, within the complex framework of the microbial consortium-immune system-nervous system axis in the human or animal organism. Although the operation of each of these systems per se is relatively well understood, their combined effects on the host organism still await further research. Drawing on recent research on host-produced and microbial low-molecular-weight neurochemicals such as biogenic amines, amino acids, and short-chain fatty acids (SCFAs), we suggest that these mediators form a part of a universal neurochemical Blanguage.^It mediates the whole gamut of harmonious and disharmonious interactions between (a) the intestinal microbial consortium, (b) local and systemic immune cells, and (c) the central and peripheral nervous system. Importantly, the ongoing microbiota-host interactivity is bidirectional. We present evidence that a large number of microbially produced low-molecular-weight compounds are identical or homologous to mediators that are synthesized by immune or nervous cells and, therefore, can bind to the corresponding host receptors. In addition, microbial cells specifically respond to host-produced neuromediators/ neurohormones because they have adapted to them during the course of many millions of years of microbiota-host coevolution. We emphasize that the terms Bmicrobiota^and Bmicrobial consortium^are to be used in the broadest sense, so as to include, apart from bacteria, also eukaryotic microorganisms. These are exemplified by the mycobiota whose role in the microbial consortium-immune system-nervous system axis researchers are only beginning to elucidate. In light of the above, it is imperative to reform the current strategies of using probiotic microorganisms and their metabolites for treating and preventing dysbiosis-related diseases. The review demonstrates, in the example of novel probiotics (psychobiotics), that many target-oriented probiotic preparations produce important side effects on a wide variety of processes in the host organism. In particular, we should take into account probiotics' capacity to produce mediators that can considerably modify the operation of the microecological, immune, and nervous system of the human organism.

Введение Рассеянный склероз (РС)-хроническое демиелинизирующее и нейродегенеративное заболевание ЦНС с аутоиммунным механизмом развития [1]. Этиология РС до конца не уточнена. Полагают, что РС является мультифакторным заболеванием, в развитии которого определенную роль играют генетическая предрасположенность, инфекционные агенты (прежде всего вирусы), воздействие психоэмоционального стресса, недостаточность витамина D и курение [2-9]. В последнее время особое внимание среди этиологических факторов заболевания привлекает изменение кишечной микробиоты организма [10]. Кишечная микробиота человека представляет собой сообщества микроорганизмов, населяющих поверхность и полости его тела. Согласно последним данным, в организме взрослого человека находится примерно 100 триллионов бактерий и более квадриллиона вирусов, что во много раз превышает собственное количество клеток организма [11-13].

СОБСТВЕННЫЕ ИССЛЕДОВАНИЯ • OWN RESEARCH Журнал «Злокачественные опухоли» • №4-2015 г. (15) • www.malignanttumours.org Около 70% случаев рака молочной железы (РМЖ) представляют собой гормон-чувствительные опухоли, и основным методом лечения таких опухолей является антиэстрогеновая терапия. На данный момент времени, существенной проблемой остается развитие эндокринной резистентности при применении гормонального лечения. В статье приведен обзор литературы о сигнальных путях, регулирующих опухолевый рост, механизмах развития эндокринной резистентности и о возможных путях ее преодоления.

Introduction: Laparoscopic pancreatic surgery remains one of the most difficult and challenging applications of minimally invasive surgical approaches in spite of great development of these techniques nowadays. Patients and methods: One hundred and thirty one patients with periampullar tumors that planed for laparoscopic Whipple procedure (LPD) between January 2007 and July 2015 were analyzed. In cases when the SMV/PV resection was necessary due to tumor invasion it was performed. Results: One hundred and fourteen consecutive total laparoscopic PD were successfully performed. There were 66 females and 48 males. The mean age was 61 AE 10.9 years. Median BMI 24kg/m2 (range 16 to 37 kg/m2). Fourteen patients (12%) were operated on for benign and 100 (88%) for malignant lesions. Standard Whipple (n69;60%patients), pylorus-preserving PD (n45;40%patients. Median OT was 415min (range 240e 765min). Median blood lossÀ200ml (range 50e2100 ml). Clinical significant pancreatic fistula (n20;17%patients); grade B (n14;12% patients, grade C (n6;5%patients). Delayed gastric emptying grade B (n5;4,5% patients), grade C (n5;4,5% patients) patients. Postpancreatectomy haemorrhage grade A (n2;1,7% patients), grade B (n8;7% patients, grade C (n3;2,6% patients). Pancreatic adenocarcinoma (n59;51.9%), ampullary adenocarcinoma (n27;23.9%), chronic pancreatitis (n12;10.6%), common bile duct carcinoma (n8;7.1%), IPMN (n2;1.7%), duodenal adenoma (n1;0.8%), undifferentiated cancer of pancreas (n1;0.8%), undifferentiated cancer of common bile duct (n1;0.8%), undifferentiated cancer of duodenum (n1;0.8%), neuroendocrine carcinoma (n1;0.8%), solid pseudopapillary tumor (n1;0.8%). Eight patients had different types of venous resections. Conclusion: Total LPD demands high technical skills from the whole surgical team. Morbidity and mortality are the same like in open procedures, time of the operation is higher at the initial experience and becomes practically equal after performing 50 cases. Major venous reconstruction is possible if needed.

Results: 60% of the patients with pancreatitis carrying a CFTR mutation had other mutation(s) that is associated with pancreatitis, while 39% of non-CFTR group with pancreatitis had other genetic susceptibility factor(s). There was no significant difference between CFTR and non-CFTR groups regarding the frequency of recurrent acute (28.6% vs. 24.2%) or chronic pancreatitis (14.3% vs. 11%), age of onset (11.5 vs. 12.2 years of age) and length of hospitalization (9.6 vs. 13.7 days). Conclusion: The presence of CFTR mutations did not influence significantly the clinical outcome of patients with childhood-onset pancreatitis. Studying higher number of CFTR-carriers with pancreatitis is necessary for precise clinical interpretation of our data.

Background: The data regarding risk factors of postoperative deep venous thrombosis (DVT) and pulmonary embolism (PE) following pancreaticoduodenectomy (PD) are limited. The purpose of this study is to identify independent risk factors of both DVT and PE in patients undergoing PD for malignancy or neoplasm. Methods: Patients who underwent PD for malignancy or neoplasm from 2010 to 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Multivariate analysis using logistic regression was used to identify independent risk factors for post-operative DVT and PE. Results: 17,742 patients underwent PD for cancer or neoplasm during this time period. Subjects were predominately white (78.4%) males (53.6%) with length of stay (LOS) of 9 (7e14) days. 30-day mortality was 1.4%. Rates of post-operative DVT and PE were 2.7% and 1.1%, respectively. Only 42 (21.5%) patients with a diagnosis of PE had concomitant DVT reported. PE was diagnosed on hospital readmission in 24 (12.3%) patients. Independent risk factors for the development of DVT were ASA score 3 (OR 1.39 [1.05e1.85]), operative time >6 hours (OR 1.47 [1.19e1.83]), LOS 1 week (OR 3.63 [2.62e5.03]), and presence of bleeding disorder (OR 2.02 [1.29e3.17]). PE was independently associated with LOS 1 week (OR 3.37 [2.08e5.47]), malignancy (OR 1.66 [1.13e2.43]), and post-operative DVT (OR 8.26 [5.56e12.23]). Overall complication rate was increased when DVT or PE occurred (OR 4.31 [3.59e 5.17] and 4.21 [3.17e5.59]). Conclusion: Multiple risk factors are independently associated with post-operative DVT and PE following PD. A majority of patients with post-operative PE did not have a preceding diagnosis of DVT. Further investigation into the routine use of DVT screening and extended chemoprophylaxis in high-risk patients should be considered.