Picroliv accelerates epithelialization and angiogenesis in rat wounds

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Angiogenesis plays a central role in wound healing. Earlier, we have shown that picroliv, a natural product obtained from the roots of Picrorhiza kurrooa, up-regulates the expression of vascular endothelial growth factor in human umbilical vein endothelial cells and of insulin-like growth factor in rats during hypoxia. In the present study, we have investigated the effect of picroliv in an ex vivo rat aorta ring model of angiogenesis. Picroliv enhanced the sprouting and migration of endothelial cells. We also investigated punch wound healing on days 4 and 7 after wounding by histology, morphometry and collagenization. The data showed improved re-epithelialization, neovascularization and migration of various cells such as endothelial, dermal myofibroblasts and fibroblasts into the wound bed after picroliv treatment. Immunohistochemical localization showed increased VEGF and alpha smooth muscle actin staining consistent with an increased number of microvessels in granulation tissue. These findings suggest that picroliv could be developed as a therapeutic angiogenic agent for the restoration of the blood supply in diseases involving inadequate blood supply such as limb ischemia, ischemic myocardium and wound healing.     

Bacterial biopolymers: From production to applications in biomedicine

Bacterial polymers obtained tremendous attention over the decades owing to its widespread use in biomedical applications. A better understanding on metabolic pathways and development of improved production strategies through metabolic engineering tools to synthesize tailor made polymer materials to meet their applicability in biomedicine. This review focuses on wide range of these biocompatible polymeric materials include polysaccharides, polyesters, polyamides and polyphosphates with wound healing, antioxidant, antitumor, antimicrobial activities. This review focuses on the advantages of various biomaterials to obtain controlled/sustained drug release and tissue engineering applications in biomedical field and the applications of microbial polysaccharides as drugs in pharmaceutical industry. This review describes the most prominent biomedical applications of bacterial biopolymer material as wound healing bandages, drug delivery, tissue engineering, ortho-dental applications and hydrogels. Reviews the future aspects based on economic feasibility and challenges in mass production and downstream processing of biopolymers and its tailor made synthesis to accomplish diverse applications.     

Bacterial bioactive metabolites as therapeutic agents: From production to action

Bacterial metabolites are one of the primary sources of drugs that we currently use to treat several diseases. However, bacterial drug discovery and development is a challenging and time-consuming process, and the emergence of new diseases and the development of resistance to currently available drugs demand the discovery of new metabolites with better biological activities. The new advancements in microbial technology, omics, genome and metabolic engineering, synthetic biology and the interdisciplinary approach of these fields overcome the hurdles in drug discovery and heterologous synthesis from bacteria. The gut microbiome performs a vital role in sustaining human health and aids in tackling various diseases. The metabolites produced by the gut microbiome act as an energy source for colon epithelium, maintain pH, help in cell differentiation and induces apoptosis in abnormal cells. The review discusses about the bacterial derived bioactive compounds, advancements and technologies in bacterial synthesis of bioactive sources and genomic and synthetic biology methods for the bioprospecting of bacterial metabolites. Since the gut microbiome relates to colon health, we have also discussed the techniques comprising probiotics, prebiotics, microbiome transplantation, toxins, and bacteriocins capable of preventing and managing colon associated health condition. Future directions in bacterial bioactive metabolite production are also discussed.     

Isolated Junctional Tachycardia in a Child After Noncardiac Surgery: An Uncommon Clinical Presentation

Isolated junctional tachycardia is rare in children but has been reported after cardiac surgery. To date, it has not been reported after noncardiac surgery. This report describes the case of a 3-year-old boy with no cardiac history who experienced transient junctional tachycardia after a right pyeloplasty. Medical therapy was not prescribed initially due to lack of symptoms. However, symptomatic junctional tachycardia recurred, prompting institution of oral beta-blocker therapy. Isolated junctional tachycardia should not be overlooked in the differential diagnosis of pediatric supraventricular tachycardia after noncardiac surgery.     

Striatal pleiotrophin overexpression provides functional and morphological neuroprotection in the 6-hydroxydopamine model

Neurotrophic factors are integrally involved in the development of the nigrostriatal system and in combination with gene therapy, possess great therapeutic potential for Parkinson's disease (PD). Pleiotrophin (PTN) is involved in the development, maintenance, and repair of the nigrostriatal dopamine (DA) system. The present study examined the ability of striatal PTN overexpression, delivered via psueudotyped recombinant adeno-associated virus type 2/1 (rAAV2/1), to provide neuroprotection and functional restoration from 6-hydroxydopamine (6-OHDA). Striatal PTN overexpression led to significant neuroprotection of tyrosine hydroxylase immunoreactive (THir) neurons in the substantia nigra pars compacta (SNpc) and THir neurite density in the striatum, with long-term PTN overexpression producing recovery from 6-OHDA-induced deficits in contralateral forelimb use. Transduced striatal PTN levels were increased threefold compared to adult striatal PTN expression and approximated peak endogenous developmental levels (P1). rAAV2/1 vector exclusively transduced neurons within the striatum and SNpc with approximately half the total striatal volume routinely transduced using our injection parameters. Our results indicate that striatal PTN overexpression can provide neuroprotection for the 6-OHDA lesioned nigrostriatal system based upon morphological and functional measures and that striatal PTN levels similar in magnitude to those expressed in the striatum during development are sufficient to provide neuroprotection from Parkinsonian insult.     

Renal cell carcinoma with IVC and atrial thrombus: A single centre's 10 year surgical experience

Renal cell carcinoma (RCC) propagates into the IVC in 4% of cases with 1% extending into the right atrium. Radical surgical resection remains the definitive curative/palliative treatment in those without significant metastases. The aim was to review our experience in patients with different levels of IVC involvement, cardiopulmonary bypass (CPB) and perioperative/long term outcomes.Patients and methodsFrom 2001 to 2012, 24 radical nephrectomies with IVC thrombectomy were performed. A retrospective chart review was undertaken to record demographics, presenting symptoms, duration of surgery, peri-operative transfusion, CPB and peri-operative complications, tumour grade/stage, and patient survival.ResultsWe identified 24 patients (18 male, Age median 59 range 35–78). The commonest presenting symptoms were weight loss, pain and haematuria. The majority of tumours were right sided (n = 17) with 8 having lung metastases at presentation. Thrombus level was 16 (infradiaphragmatic), 2 (supradiaphragmatic), 6 (intra-atrial). 15 patients required sternotomy for vascular control and 9 required CPB both with a significantly longer operative time compared (6.1 ± 3.5 vs. 7.2 ± 1.2 vs. 3.5 ± 1.1 h, respectively). Peri-operative complications (n = 21) included cardiopulmonary, renal, gastrointestinal and septic problems. There were 2 peri-operative deaths. Blood transfusion was significantly less in those not requiring sternotomy or CPB using the "Cell Saver" device. The majority were Fuhrman grade 3 (n = 16) and clear cell type (n = 14). Overall 3-year survival was 100% (Laparotomy only), 40% (sternotomy + cross-clamp), and 20% (CPB).ConclusionsIVC thrombectomy has significant morbidity and requires careful patient selection and a multi-disciplinary approach to optimise patient outcomes. In this series, the level of IVC thrombus and requirement for CPB directly affects patient morbidity and outcome.     

Prognostic importance of DNA repair gene polymorphisms of <Emphasis Type="Italic">XRCC1</Emphasis> Arg399Gln and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln in lung cancer patients from India

Purpose Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive. Methods In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population. Logistic regression models were fit to examine the relationship between the log odds of lung cancer and each covariate. Overall Survival in relation to various genotypes and clinicopathological factors were analyzed using Kaplan Meier estimates and hazard ratios were calculated using Cox Regression analysis. Results The carriers of XRCC1 399 AA genotypes were at higher risk of lung cancer (OR = 2.1, 95% CI:1.224–3.669, P = 0.007) than carriers of GG genotype. Subjects carrying 751 AC genotype were at an increased risk of carcinoma of the lung (OR = 1.8; 95% CI:1.233–2.807, P = 0.003) than subjects with AA genotypes. Compared to the XRCC1 399 GG/ XPD 751 AA reference genotype, the combined variants, XRCC1 399 GG/ XPD 751 AC+CC (OR = 1.9, 95% CI: 1.037–3.481), P = 0.03), XRCC1 399 GA+AA/ XPD 751 AA (OR = 1.7, 95% CI: 1.020–2.833, P = 0.04), XRCC1 399 GA+AA/XPD 751 AC+CC (OR = 2.7, 95% CI: 1.582–4.864, P = 0.01), had significantly higher odds ratios. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival, the risk being significant for the XRCC1 gene polymorphism (P = 0.01 by log-rank test). The hazard of dying was significant for the XRCC1 399 AA genotype (HR = 3.04, 95%CI: 1.393–6.670, P = 0.005). Higher tumour stage also came out as significant predictors of patient death. Conclusions These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.     

Laparoscopic drainage of cryptogenic liver abscess

Background

To retrospectively compare the outcomes of percutaneously drained and laparoscopically drained liver abscesses.

Methods

Eight-five consecutive patients with radiological evidence of liver abscess were treated at National University Hospital of Singapore from 2005 to 2011. Multivariable logistic regression was used to identify failures of intervention. This was defined as persistent objective signs of sepsis. Complications, length of antibiotic therapy, and hospital stay were recorded but not used as indicators for failure of intervention. A propensity score analysis was used to adjust for possible confounders.

Results

Twenty-seven (40.3 %) patients in the percutaneous group did not respond to primary intervention compared to 2 patients (11.1 %) in the laparoscopic group (p = 0.020). Two patients within the percutaneous group died from progression of sepsis despite intervention. In the multivariate model with propensity score, laparoscopic drainage had a protective effect against failure compared to percutaneous drainage of liver abscess (odds ratio [OR], 0.03; 95 % confidence interval [CI], [0–0.4]; p = 0.008). There were no differences in complications related to the intervention (p = 0.108). Mean duration of antibiotics (p = 0.437) and hospital stay (p = 0.175) between the groups was similar.

Conclusions

Laparoscopic drainage of cryptogenic liver abscesses should be considered as an option for drainage of liver abscess.     

Health behaviors among breast,prostate, and colorectal cancer survivors: a US population-based case-control study,with comparisons by cancer type and gender

Purpose

The aim of this study is to compare health behaviors between breast, prostate, female, and male colorectal cancer survivors to noncancer controls, stratified by short- and long-term survivors, and between cancer types and genders.

Methods

A 3:1 population-based sample of breast (6,259), prostate (3,609), female colorectal (1,082), and male colorectal (816) cancer survivors from the 2009 Behavioral Risk Factor Surveillance System survey were matched to noncancer controls on age, gender, race/ethnicity, income, insurance, and region of the US. The likelihood of flu immunization, physical check-up, cholesterol check, body mass index (BMI), physical activity, diet (5-A-Day), smoking, and alcohol use were compared between groups using binomial logistic regression models.

Results

Short-term breast cancer survivors were significantly more likely to meet multiple behavioral recommendations, than controls, but the likelihood decreased in the long term. Breast and female colorectal cancer survivors were up to 2.27 (95 % CI 1.90, 2.71) and 1.89 times more likely (95 % CI 1.60, 2.24) to meet the 5-A-Day and BMI recommendations, up to 0.54 times less likely (95 % CI 0.46, 0.64) to drink any alcohol, but were 0.68 times less likely (95 % CI 0.49, 0.95) to meet the physical activity recommendation, compared to prostate and male colorectal cancer survivors.

Conclusions

Some cancer survivors may engage in better health behaviors shortly after diagnosis, but the majority of cancer survivors do not have better health behaviors than individuals without a history of cancer. However, a consistent pattern of behavioral differences exist between male and female cancer survivors.

Implications for Cancer Survivors

Gender differences in health behaviors among cancer survivors may be influenced by perceptions of masculinity/femininity and disease risk. Ongoing health behavioral promotion and disease prevention efforts could be improved by addressing these perceptions.