A study of anti-cancer effects of Funalia trogii in vitro and in vivo

Extracts of natural products have been used for many years for health benefits. We report on an in vitro and in vivo study into the anti-tumour efficacy of an aqueous extract of the mycelial form of basidiomycete, Funalia trogii. A variety of biological assays were used to show that a 4 h exposure of HT29, LNCaP, PC3, MCF-7 and MDA-MB-231 tumour cells to extract (0.5-5.0 mg/ml) resulted in significant cytotoxicity. In a clonogenic assay, IC₅₀ values were found to range from 0.4-0.72 mg/ml; exposing fibroblast cells to the extract resulted in no cell kill. The extract resulted in significant cell kill in proliferating endothelial cells but had no toxicity to quiescent cells, this is useful in targeting tumour tissue since endothelial cells in tumours proliferate more rapidly that those found in other parts of the body. When tumours grown in immune compromised mice were injected intratumourally with extract (5 mg/ml twice a week for two weeks), a 9 day tumour growth delay was observed. The results indicate that the mycelial extract of F. trogii has a promising anti-tumour property.     

Admissions and costs to acute hospitals resulting from road traffic crashes, 2005-2009

Road traffic crashes (RTCs) remain a leading cause of death and injury. The aim of this study was to explore the use of hospital data as a source of RTC-related injury data in Ireland, as current systems are believed to under-estimate the burden. Information on inpatient discharges for years 2005-2009, admitted with RTC-related injuries were extracted from HIPE. There were 14,861 discharges; 9,661 (65.0%) were male, with an average age of 33 years. The median length of stay was two days. The most common diagnosis was head injury (n = 4,644; 31.2%). The average inpatient hospital cost was Euro 6,395 per discharge. 1,498 (10.1%) were admitted to intensive care units. This study has identified 3.5 times more serious injuries (14,861) than identified in the Road Safety Authority (RSA) statistics (4,263) indicating that the extent of road injuries is greater than previously estimated. Hospital data could be used annually in conjunction with RSA and other data; ideally the data should be linked.     

Asymmetrical lateral ventricular enlargement in Parkinson's disease

Background:  A recent case report suggested the presence of asymmetrical lateral ventricular enlargement associated with motor asymmetry in Parkinson's disease (PD). The current study explored these associations further.
Methods:  Magnetic resonance imaging (3T) scans were obtained on 17 PD and 15 healthy control subjects at baseline and 12–43 months later. Baseline and longitudinal lateral ventricular volumetric changes were compared between contralateral and ipsilateral ventricles in PD subjects relative to symptom onset side and in controls relative to their dominant hand. Correlations between changes in ventricular volume and United Parkinson's disease rating scale motor scores (UPDRS-III) whilst on medication were determined.
Results:  The lateral ventricle contralateral to symptom onset side displayed a faster rate of enlargement compared to the ipsilateral ( P  = 0.004) in PD subjects, with no such asymmetry detected ( P  = 0.312) in controls. There was a positive correlation between ventricular enlargement and worsening motor function assessed by UPDRS-III scores ( r  = 0.96, P  < 0.001).
Discussion:  There is asymmetrical lateral ventricular enlargement that is associated with PD motor asymmetry and progression. Further studies are warranted to investigate the underlying mechanism(s), as well as the potential of using volumetric measurements as a marker for PD progression.     

Bioreductive drugs: from concept to clinic

One of the key issues for radiobiologists is the importance of hypoxia to the radiotherapy response. This review addresses the reasons for this and primarily focuses on one aspect, the development of bioreductive drugs that are specifically designed to target hypoxic tumour cells. Four classes of compound have been developed since this concept was first proposed: quinones, nitroaromatics, aliphatic and heteroaromatic N-oxides. All share two characteristics: (1) they require hypoxia for activation and (2) this activation is dependent on the presence of specific reductases. The most effective compounds have shown the ability to enhance the anti-tumour efficacy of agents that kill better-oxygenated cells, i.e. radiation and standard cytotoxic chemotherapy agents such as cisplatin and cyclophosphamide. Tirapazamine (TPZ) is the most widely studied of the lead compounds. After successful pre-clinical in vivo combination studies it entered clinical trial; over 20 trials have now been reported. Although TPZ has enhanced some standard regimens, the results are variable and in some combinations toxicity was enhanced. Banoxantrone (AQ4N) is another agent that is showing promise in early phase I/II clinical trials; the drug is well tolerated, is known to locate in the tumour and can be given in high doses without major toxicities. Mitomycin C (MMC), which shows some bioreductive activation in vitro, has been tested in combination trials. However, it is difficult to assign the enhancement of its effects to targeting of the hypoxic cells because of the significant level of its hypoxia-independent toxicity. More specific analogues of MMC, e.g. porfiromycin and apaziquone (EO9), have had variable success in the clinic. Other new drugs that have good pre-clinical profiles are PR 104 and NLCQ-1; data on their clinical safety/efficacy are not yet available. This paper reviews the pre-clinical data and discusses the clinical studies that have been reported.     

Molecular characterization of the Caenorhabditis elegans ALP/Enigma gene alp-1.

Members of the ALP/Enigma family of PDZ-LIM proteins play a role in cytoskeletal anchorage and mutations in at least one member of this family are associated with human cardiomyopathy. Here, we describe the analysis of the Caenorhabditis elegans alp-1 gene. alp-1 is predicted to encode the entire nematode ALP/Enigma protein family, consisting of one ALP-related protein with a single LIM domain and three Enigma-like proteins containing four LIM domains. We demonstrate that the ALP-1 proteins are expressed in muscle cells, where they localize to actin anchorage and muscle attachment sites. We show that the PDZ domain of the ALP-1 proteins is sufficient to target the protein to the dense bodies, which are important actin anchorage sites in C. elegans body wall muscle. We demonstrate that the C. elegans ALP/Enigma proteins are also localized to cell-cell junctions and to both epithelial and muscle cell nuclei. These findings suggest new roles for the ALP/Enigma protein family that may lead to the understanding of their involvement in cardiomyopathy.     

Urinary tract infections during pregnancy

OBJECTIVE: To provide a comprehensive review of urinary tract infections (UTIs) during pregnancy. All aspects of UTIs, including epidemiology, pathogenesis, resistance, clinical features, diagnosis, treatment, and prevention, were reviewed. DATA SOURCES: MEDLINE (1966-August 2003) and Cochrane Library searches were performed using the key search terms urinary tract infection, pyelonephritis, cystitis, asymptomatic bacteriuria, and resistance. STUDY SELECTION AND DATA EXTRACTION: All article abstracts were evaluated for relevance. Only articles pertaining to pregnancy were included. The majority of published literature were review articles; the number of original clinical studies was limited. DATA SYNTHESIS: UTIs are the most common bacterial infections during pregnancy. They are characterized by the presence of significant bacteria anywhere along the urinary tract. Pyelonephritis is the most common severe bacterial infection that can lead to perinatal and maternal complications including premature delivery, infants with low birth weight, fetal mortality, preeclampsia, pregnancy-induced hypertension, anemia, thrombocytopenia, and transient renal insufficiency. Enterobacteriaceae account for 90% of UTIs. The common antibiotics used are nitrofurantoin, cefazolin, cephalexin, ceftriaxone, and gentamicin. CONCLUSIONS: Therapeutic management of UTIs in pregnancy requires proper diagnostic workup and thorough understanding of antimicrobial agents to optimize maternal outcome, ensure safety to the fetus, and prevent complications that lead to significant morbidity and mortality in both the fetus and the mother.     

Patch closure of aortic annulus mycotic aneurysms

Twenty-three patients with bacterial endocarditis and mycotic aneurysms of the aortic annulus were treated between 1978 and 1985. There were 18 men and 5 women ranging from 24 to 72 years old. All patients had congestive heart failure and positive blood cultures as a complication of the endocarditis and were in New York Heart Association (NYHA) Functional Class III or IV. The aneurysm complicated late prosthetic valve endocarditis in 7 patients and native valve endocarditis in 16. The most common infecting organisms were streptococci (12 patients) and staphylococci (7 patients). The noncoronary sinus was the most frequent site for aneurysm formation. Following debridement of the abscess cavity, the orifice of the aneurysm was closed with a patch of Dacron in 20 patients and autologous pericardium in 3. A prosthetic valve (18 bioprosthetic and 5 mechanical) was secured to the noninfected portion of the native annulus and to the patch at the level of annulus. There were 3 deaths, 1 perioperative and 2 late, each without evidence of residual infection or aortic insufficiency. There are 20 late survivors (87%). After a mean follow-up of 1 year, all patients are in NYHA Functional Class I. Patch closure of mycotic aneurysms involving the aortic annulus permits aggressive debridement of the abscess cavity and affords closure of the orifice without tension. The prosthetic valve can be seated at the level of the native annulus, thus avoiding complicated reconstructive procedures of the aortic root and coronary arteries. This technique is an effective alternative in selected cases of mycotic aneurysms involving the aortic annulus.     

Thoracoscopic lung biopsy.

Progress in instrumentation and techniques developed for laparoscopic surgery have paved the way for a resurgent interest in thoracoscopic procedures. Traditional thoracoscopy was limited by access, restricted visualization, and surgical devices. Recent cases provided an opportunity to successfully perform thoracoscopic pulmonary wedge excisions using state-of-the-art technology and instruments adapted from laparoscopy. These preliminary cases provided an opportunity to modify and adapt these techniques to thoracic procedures. Video thoracoscopy is rapidly evolving in both methods and instrumentation.