Prostate-Associated Gene 4 (PAGE4): Leveraging the Conformational Dynamics of a Dancing Protein Cloud as a Therapeutic Target.

Prostate cancer (PCa) is a leading cause of mortality and morbidity globally. While genomic alterations have been identified in PCa, in contrast to some other cancers, use of such information to personalize treatment is still in its infancy. Here, we discuss how PAGE4, a protein which appears to act both as an oncogenic factor as well as a metastasis suppressor, is a novel therapeutic target for PCa. Inhibiting PAGE4 may be a viable strategy for low-risk PCa where it is highly upregulated. Conversely, PAGE4 expression is downregulated in metastatic PCa and, therefore, reinstituting its sustained expression may be a promising option to subvert or attenuate androgen-resistant PCa. Thus, fine-tuning the levels of PAGE4 may represent a novel approach for personalized medicine in PCa

Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease

Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole

Self-expandable metals stents – a novel treatment option for gastrointestinal strictures

Catedra Chirurgie Nr. 1 „N. Anestiadi” şi Laboratorul Chirurgie Hepato-Pancreato-Biliară, USMF „N. Testemițanu”, Centrul Național Ştiințifico-Practic de Medicină Urgentă, Chişinău, Moldova, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Stenturile metalice auto-expandabile sunt tot mai frecvent utilizate în tratamentul stricturilor de diversă etiologie ale tractului digestiv, fie ca metodă definitivă sau soluție temporară. Scopul studiului: Evaluarea eficacității şi rezultatelor utilizării stenturilor metalice auto-expandabile în tratamentul stricturilor gastro- intestinale. Material şi metodă: Șapte pacienți consecutivi: F (n=4), M (n=3) cu vârsta medie 55.43±1.83 ani au fost incluşi în studiu. Etiologia şi localizarea stricturilor a fost: esofag (n=5) benign; colon sigmoid (n=1) malign şi piloroduodenal (n=1) malign. Au fost utilizate următoarele tipuri de stenturi: HV-ella stent (n=3), FerX-ELLA Esophageal Stent - Boubella (n=2), Piloroduadenal Ella (n=1) şi Colorectal Ella (n=1) ELLA-CS, Hradec-Kralove, Czech Republic. Rezultate: În toate cazurile plasarea stenturilor a fost cu succes. Stentarea a fost permanentă în două cazuri de strictură malignă, iar în 5 cazuri stenturile au fost înlăturate la 16.60±4.83 (2-28) zile. Rata complicațiilor a fost 28.57% (migrarea stentului-1 obstrucția valvei anti-reflux-1). În ambele cazuri complicațiile au fost rezolvate non-operator. Concluzii: Stenturile metalice auto-expandabile reprezintă alternativă viabilă de tratament al stricturilor maligne şi benigne ale tractului digestiv. Deşi rata complicaților a fost semnificativă, acestea pot fi rezolvate endoscopic. Sunt necesare studii suplimentare pe loturi mai mari de pacienți pentru formularea concluziilor finale.Background: Self-expandable metals stents have increasingly been used as a temporary or permanent device as a bridge to surgery or chemoradiotherapy in patients with gastrointestinal malignant and benign disease. Study aim: To evaluate the efficacy and outcomes of self-expandable metals stents used for the management of gastrointestinal strictures. Material and Methods: Seven consecutive patients: F (n=4), M (n=3) with the mean age 55.43±1.83 years were included in the study. Stricture etiology and location was: esophageal (n=5) benign; colorectal (n=1) malignant and piloroduodenal (n=1) malignant. Type of stents used: HV-ella stent (n=3), FerX-ELLA Esophageal Stent - Boubella (n=2), Piloroduadenal Ella (n=1) and Colorectal Ella (n=1) ELLA-CS, Hradec-Kralove, Czech Republic.Results: In all cases the stents were successfully deployed. Stenting was permanent for two cases of malignant strictures, while in 5 patients the stents were removed after 16.60±4.83 (2-28) days. The stent induced complication rate was 28.57% (stent migration n=1 and antireflux valve obstruction n=1). In both cases the complications were managed non-operatively. Conclusions: Self-expandable metals stents are a viable treatment option in both malignant and benign strictures of the gastrointestinal tract. Although significant, the complications are amendable to endoscopic management. Further studies on larger groups of patients are mandatory in order to drag final conclusions

Intertarsal Joint Stabilization in a Bateleur Eagle (Terathopius ecaudatus) Using a Novel Application of a Braided Suture and Titanium Button System.

A 32-year-old adult captive male bateleur eagle (Terathopius ecaudatus) with a history of laxity, degenerative joint disease, and varus deviation of the distal left hindlimb for several years was presented for evaluation of left hindlimb lameness and was diagnosed with chronic subluxation of the left intertarsal joint. After failing to improve with conservative management and pain medication, surgical stabilization of the joint was performed using a novel application of a braided suture and titanium button system. Unsatisfactory clinical improvement and postsurgical reevaluation indicated that the initial surgical stabilization was unsuccessful. The surgery was repeated, and the animal showed postsurgical improvement in intertarsal joint stability, weight-bearing, and lameness for a period of several years with use and adjustment of chronic pain medications. The novel surgical technique described in this case report represents an additional treatment option for management of avian intertarsal joint subluxations. Presurgical planning should consider the unique anatomic features and variability of the avian tarsometatarsus to avoid surgical complications

Microwave ablation therapy for colorectal liver metastases

BACKGROUND: The gold standard treatment for colorectal cancer liver metastases (CRCLM) is surgical resection. Unfortunately, the majority of patients with colorectal hepatic metastases are not candidates for resection. In recent years, several alternatives have emerged for patients whom are not resection candidates including modern systemic chemotherapy, targeted biologic treatments, regional therapies and local tumor ablation options. Microwave ablation (MWA) therapy is one such treatment alternative, based on thermal tissue ablation. This modality in concert with the most recent published literature on its use for patients with CRCLM will be reviewed in this paper. LITERATURE REVIEW FINDINGS: A structured review of the literature on ablative technologies was performed. In recent years, there has been an evolution from radiofrequency ablation (RFA) to microwave ablation therapy for the treatment of CRCLM. RFA has several limitations to its use and MWA theoretically avoids such limitations making it the currently preferable treatment option. There are limited publications comparing the use of RFA to MWA and limited publications on the use of microwave ablation for CRCLM. This paper will focus on the most recent data on MWA for CRCLM. This data can then be compared to the already published data on RFA. PROPOSED METHODS: Given the relative novel status for MWA as a treatment option for CRCLM, a potential disadvantage for its use is the perceived lack of knowledge across the medical professional spectrum. In an effort to expand the knowledge of MWA, the proposed outcomes for this study include creating a curriculum to be offered as a CME course focused for Primary Care Providers (PCPs) to provide a basis of clinical familiarity for its use. This effort will familiarize providers who may have patients diagnosed with CRCLM and also allow them to initiate the conversation about this therapy with their patients who may be candidates for this treatment. CONCLUSIONS: MWA therapy is a safe and effective treatment modality for CRCLM. Due to this new development in treating liver lesions originating from colorectal cancer, it’s imperative for providers to become familiar with these new technologies especially considering the high incidence of CRCLM. Therefore, a curriculum for PCPs will allow for a better understanding of this new technology and foster better provider-patient relationships

Murine fecal microbiota transplantation lowers gastrointestinal pathogen loads and dampens pro-inflammatory immune responses in Campylobacter jejuni infected secondary abiotic mice

Conventional mice are protected from Campylobacter jejuni infection by the murine host-specific gut microbiota composition. We here addressed whether peroral fecal microbiota transplantation (FMT) might be an antibiotics-independent option to lower even high gastrointestinal C. jejuni loads in the infected vertebrate host. To address this, secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally infected with C. jejuni by gavage. One week later, mice were stably colonized with more than 109 C. jejuni and subjected to peroral FMT from murine donors on three consecutive days. Two weeks post-intervention, gastrointestinal C. jejuni loads were up to 7.5 orders of magnitude lower following murine FMT versus mock challenge. Remarkably, FMT reversed C. jejuni induced colonic epithelial apoptosis, but enhanced proliferative and regenerative responses in the colon thereby counteracting pathogenic cell damage. Furthermore, FMT dampened both, innate and adaptive immune cell responses in the large intestines upon C. jejuni infection that were accompanied by less C. jejuni-induced colonic nitric oxide secretion. Our study provides strong evidence that novel probiotic formulations developed as alternative option to FMT in severe intestinal inflammatory morbidities including Clostridoides difficile infection might be effective to treat campylobacteriosis and lower pathogen loads in colonized vertebrates including farm animals

Cell-based therapies for stroke : promising solution or dead end?

The introduction of recanalization procedures has revolutionized acute stroke management, although the narrow time window, strict eligibility criteria and logistical limitations still exclude the majority of patients from treatment. In addition, residual deficits are present in many patients who undergo therapy, preventing their return to premorbid status. Hence, there is a strong need for novel, and ideally complementary, approaches to stroke management. In preclinical experiments, cell-based treatments have demonstrated beneficial effects in the subacute and chronic stages following stroke [1; 2; 3] and therefore are considered a promising option to supplement current clinical practice. At the same time, great progress has been made in developing clinically feasible delivery and monitoring protocols [4]. However, efficacy results initially reported in clinical studies fell short of expectations [5] raising concerns that cell treatment might eventually share the ‘dead end fate’ of many previous experimental stroke therapies. This Research Topic reviews some of the latest and most innovative studies to summarize the state of the art in translational cell treatments for stroke