Therapy of local recurrence after colorectal cancer

A prospective study was undertaken of the incidence, symptoms, diagnostic measures and therapy of local recurrence of colorectal carcinoma following radical surgical management. 69 (16%) out of 434 patients developed recurrence of the tumour, which was local in 51 patients (12%). Half of the latter group was symptom free at the time of diagnosis. 45 out of the 51 patients were treated by surgery, a radical operation being feasible in 25 cases. 60% of these have survived for at least 30 months. The operative mortality was very low, with only one death, although extensive surgery was necessary in most of the cases. The preliminary results of this study support the hypothesis that a postoperative follow-up programme for patients with colorectal cancer leads to early detection of local recurrence and improves the chance of cure by surgical treatment.     

Effect of heat-treated amphotericin B on renal and fungal cytotoxicity

The purpose of this investigation was to determine the cytotoxicity of amphotericin B (AMB; trade name Fungizone [FZ]) following the administration of FZ and a heat-treated form of FZ (HFZ) to LLC-PK(1) pig kidney cells and Cryptococcus neoformans var. gattii cells. HFZ was significantly less toxic to kidney cells than FZ at all concentrations tested. For both FZ and HFZ, the concentration range which resulted in a 50% reduction of the growth of fungal cells was 0.125 to 1 mg/ml. These findings suggest that heat treatment decreases AMB's renal cytotoxicity without modifying its antifungal activity.     

Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor‐loaded biomaterials

Mesenchymal stem cells (MSC) are precursor cells of mesodermal tissue and, because of their trophic phenotype, they are known to play beneficial roles in wound healing. In addition, various tissue engineering strategies are based on MSC/biomaterial constructs. As the isolation and expansion of MSCs is a long‐term process, a major goal is to develop an endogenous stem cell recruitment system that circumvents all ex vivo steps generally used for tissue engineering. Therefore collagen and silk fibroin were loaded with hepatocyte growth factor (HGF), a chemoattractant for MSCs. Collagen was mixed with HGF during polymerization, while silk fibroin and HGF were produced as fusion proteins by transgenic silkworms. To demonstrate release of active HGF, enzyme‐linked immunosorbent assay, in vitro migration assays and animal studies were performed to demonstrate MSC migration in vivo, followed by detailed examinations of the immunological effects of the biomaterials. Hepatocyte growth factor was released burst‐like, both from silk fibroin and collagen during the first 8 h and gradually for up to 168 h in vitro. Directed migration in vitro was demonstrated when MSCs were exposed to HGF. In vivo, HGF‐loaded collagen and silk fibroin were tolerated as subcutaneous implants. In addition, it was proved that endogenous MSCs were recruited from the local environment. These results show for the first time recruitment of endogenous MSCs to HGF‐loaded collagen (fast degradable) and silk fibroin scaffolds (long‐term degradable) in vitro and in vivo. This knowledge could be applied to make off‐the‐shelf, readily available constructs for use in patients with chronic wound or burns. Copyright © 2016 John Wiley & Sons, Ltd.     

Uptake of inhalable microparticles affects defence responses of macrophages infected with Mycobacterium tuberculosis H37Ra

OBJECTIVES: To investigate whether inhalable microparticles containing two anti-tuberculosis agents, isoniazid and rifampicin, evoke host-defence strategies in macrophages in addition to targeting the incorporated drugs. METHODS: Microparticles were prepared by spray-drying a homogeneous solution of drugs and poly(lactic acid) (PLA; apparent viscosity 1.1 cP). Four parts PLA and three parts rifampicin were dissolved in dichloromethane. One part isoniazid was dissolved in methanol. The two solutions were mixed in the ratio 22 : 3 at which none of the solutes precipitated. These were administered as 'nose-only' inhalations to mice or exposed to cultured J774 mouse macrophages. Targeting to lung macrophages was investigated by transmission electron microscopy. Reactive oxygen species (ROS) were estimated by a cytochrome c assay and flow cytometry. Reactive nitrogen intermediates (RNI) were assayed using Griess reagent. Cytokines in culture supernatants were estimated by ELISA. RESULTS: Treatment with inhalable microparticles targeted lung macrophages in vivo and induced intense Golgi activity in the vicinity of microparticle-containing phagosomes. Microparticles induced a respiratory burst involving NADPH oxidase and enhanced NO production by infected macrophages. Microparticle-induced NADPH oxidase activation required optimal calcium ions. Microparticles efficiently induced tumour necrosis factor-alpha (TNF-alpha) secretion by macrophages recovered from infected mice. CONCLUSIONS: Microparticle phagocytosis induces responses in infected murine macrophages that are indicative of activation of innate bactericidal mechanisms, and are inimical to bacterial survival. It is likely that such responses augment straightforward drug action on the bacterium and contribute to the unexpectedly high efficacy of microparticles in experimental tuberculosis.     

Efficient adsorption of chlorpheniramine and hexavalent chromium (Cr(VI)) from water system using agronomic waste material

In present study, we report Cornulaca-monacantha stem (CS) and its activated carbon (CS-AC) for the removal of Cr(VI) and chlorpheniramine (CP) from aqueous system. The chemical composition and surface characteristics of samples were investigated using instrumental techniques such as Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM) and energy dispersive X-ray (EDX). The surface area was determined by Brunauer-Emmett-Teller(BET) method. The BET surface area of CS-AC (288.67 m²/g) was found higher as compared to CS adsorbent (47.58 m²/g). The adsorption behavior of adsorbates was extremely dependent on the solutions pH. The maximum uptake for Cr(VI) and CP were observed at pH of 2.0 and 8.0, respectively. The equilibrium data adequately follow the Langmuir isotherm (R² = 0.98–0.99), suggesting the monolayer sorption of adsorbate molecules. Kinetic investigations indicated that sorption behavior of Cr(VI) follow the pseudo-second-order model. While in case of CP, both pseudo-second-order and Elovich model provides the higher value of regression coefficient (R²). This revealed the chemical adsorption of adsorbate molecules. Thermodynamic study indicated the feasible, spontaneous and endothermic sorption of adsorbate molecules. The regeneration study implies that adsorbent was efficiently recovered from Cr(VI) and CP under different desorbing agents.The CS-AC adsorbent was possess 89.19% and 88.45% uptake for Cr(VI) and CP after 5th cycles of desorption-adsorption, respectively. Finally, we summarize that prepared adsorbent (CS-AC) is highly proficient, versatile and cost-effectively explored for Cr(VI) and CP decontamination from water system.     

Characterization of genetic predisposition and autoantibody profile in atypical haemolytic–uraemic syndrome

We previously reported that Indian paediatric patients with atypical haemolytic–uraemic syndrome (aHUS) showed high frequencies of anti‐complement factor H (FH) autoantibodies that are correlated with homozygous deletion of the genes for FH‐related proteins 1 and 3 (FHR1 and FHR3) (FHR1/3^–/–). We now report that Indian paediatric aHUS patients without anti‐FH autoantibodies also showed modestly higher frequencies of the FHR1/3^–/– genotype. Further, when we characterized epitope specificities and binding avidities of anti‐FH autoantibodies in aHUS patients, most anti‐FH autoantibodies were directed towards the FH cell‐surface anchoring polyanionic binding site‐containing C‐terminal short conservative regions (SCRs) 17–20 with higher binding avidities than for native FH. FH SCR17–20‐binding anti‐FH autoantibodies also bound the other cell‐surface anchoring polyanionic binding site‐containing region FH SCR5–8, at lower binding avidities. Anti‐FH autoantibody avidities correlated with antibody titres. These anti‐FH autoantibody characteristics did not differ between aHUS patients with or without the FHR1/3^–/– genotype. Our data suggest a complex matrix of interactions between FHR1‐FHR3 deletion, immunomodulation and anti‐FH autoantibodies in the aetiopathogenesis of aHUS.     

The “Long Tail” and Public Health: New Thinking for Addressing Health Disparities

The prevailing approach to improving population health focuses on shifting population means through a few targeted and universal interventions. The success of this approach for eliminating health disparities depends on an assumption about the distribution of demand for such interventions. We explored whether long tail thinking from business might yield greater progress in eliminating disparities. We examined 2011 to 2013 data from 513 state and local health agency representatives in 47 states who used an online system to create 4351 small media and client reminder products promoting colorectal cancer screening.Products in the long tail were more likely to target minority groups with higher rates of colorectal cancer and lower rates of screening than Whites. Long tail thinking could help improve the public''s health and eliminate disparities.The prevailing approaches to improving population health emphasize “shifting the mean” through prevention efforts that target large groups at high risk or through mass environmental control interventions that encourage small but universal changes in individual behavior.1 This approach has led to the search for “blockbuster” public health interventions that can have the largest effects on determinants of population health and individual behavior. An underlying assumption in both approaches is that prevention opportunities tend to focus on a few groups or a generalized public.The implication is that people falling outside this limited number of groups either collectively have a small impact on population health or can effectively be lumped into one of the larger groups. In popular terms, we often see this as the “80/20” rule, in which 80% of a problem can be solved by understanding and solving 20% of the cases. Whether this holds for population health and the elimination of health disparities depends on understanding the shape of the underlying distribution of prevention opportunities.In a compelling critique, Frohlich and Potvin argue that the prevailing population approach may have the unintended consequence of exacerbating health disparities.2 Disease risk, they point out, varies not just by behavioral risk factors but also by socially defined groups that vary in their exposure to fundamental risks, for example, low education and low socioeconomic status. Broadly targeted population interventions that focus primarily on behavioral determinants may not be as effective under these conditions or with these groups. Frohlich and Potvin propose that population approaches be complemented by a “vulnerable subgroups” approach that is intersectoral to address core risks that lie outside the realm of health and that is participatory to involve vulnerable groups in developing appropriate, population-specific solutions.We have considered whether long tail thinking applied to public health might lead to vulnerable subgroup approaches that yield greater progress in reducing health disparities. Long tailed thinking stems from new business models that recognize that selling small quantities of many niche items can be more profitable than is selling a few blockbuster items. In The Long Tail, Anderson’s bestselling book on the future of business, he argues that (1) niche markets—subsets of consumers interested in particular products—are more accessible today than ever, and (2) although the demand for any given niche-focused product will be limited, there are so many niches that collectively these products make up a huge market.3In business, the term “long tail” refers to a distribution of product sales in which a few products in the head of the distribution are blockbuster successes that have widespread appeal and generate substantial sales, followed by a much greater number of niche products that each have narrower appeal and generate only nominal sales (i.e., the long tail of the distribution; Figure 1). Anderson demonstrates that in many cases this long tail of niche products generates sales and profits that rival those of products with mass appeal and explains how new thinking and new technologies make it possible to realize these profits.Open in a separate windowFIGURE 1—The long tail of niche-targeted products: 2011–2013.Understanding how and why businesses profit from this long tail of niche products has the potential to transform our thinking about strategies to improve the public’s health. Its implications are particularly profound for helping reduce health disparities—the inequalities in health outcomes that disproportionately affect a long and diverse “tail” of “niche” populations whose needs may not be adequately addressed by approaches designed for the general population. Focusing collectively on the universe of disparity niches may yield significant population health benefits. But it would also require new approaches and new tools, as the economies of scale in distributing a few products to many people are lost.We have described the long tail perspective, examined how its key tenets apply to public health using 2011 to 2013 data from a national online health communication system, and discussed the implications of both for public health.