The supportive care needs of men with prostate cancer (2000)

The diagnosis and subsequent treatment of prostate cancer is followed by a range of significant disease specific and iatrogenic sequelae. However, the supportive care needs of men with prostate cancer are not well described in the literature. The present study assesses the supportive care needs of men with prostate cancer who are members of prostate cancer self-help groups in Queensland, Australia. In all, 206 men aged between 48 and 85 years (mean = 68) completed the Supportive Care Needs Survey (SCNS) (62% response). The SCNS is a validated measure assessing perceived need in the domains of psychological needs, health system and information needs, physical and daily living needs, patient care and support, and sexuality. Items assessing need for access to services and resources were also included. One third of the sample reported a moderate to high need for help for multiple items in the sexuality, psychological and health system and information domains. Younger men reported greater need in the sexuality domain; living in major urban centres was predictive of greater psychological need; being closer to the time of diagnosis was related to greater need for help in the physical and daily living domain; having prostate cancer that is not in remission, having received radiation therapy, and lower levels of education were predictive of greater need for help in patient care and support. Of the total sample, 55% of men had used alternative cancer treatments in the past 12 months, with younger and more educated men more likely to use alternative therapies. Interventions in sexuality, psychological concerns and informational support are priorities for men with prostate cancer. Copyright (C) 2001 John Wiley & Sons, Ltd.

Unconventional integrin-ligand interactions

Integrins are cell surface adhesion and signaling receptors. Cells use integrins to attach to the extracellular matrix and to other cells, as well as for sensing their environment. In addition to adhesion and migration, integrins have been shown to be important for many biological processes including apoptosis, cell proliferation, and differentiation into specific tissues. Many important next generation biological drugs inhibit integrin functions. Thus, research into interactions between integrins and their ligands under different physiological and pathological conditions is not only of academic interest, but is also important for the field of drug discovery. In this Ph.D. project, the functions of integrin-ligand interactions were studied under different physiologically interesting conditions including 1) human echovirus 1 binding to integrin α2β1, 2) integrin α2β1 binding to collagen under flow conditions, 3) integrin α2β1 binding to a ligand in the presence of the angiogenesis inhibitor histidine rich glycoprotein (HRG) and 4) integrin binding to posttranslationally citrullinated ligands. As a result of the project, we could show that for each condition the integrin-ligand interaction is somewhat unconventional. 1) Echovirus 1 binds only to non-activated conformations of integrin α2β1. 2) Surprisingly, the non-activated conformation is also the primary conformation of integrin α2β1 when it binds to collagen under flow conditions, like when platelets adhere to subendothelial collagen in vascular injuries. In addition, the pre-activation of integrin α2β1 does not increase adhesion under flow. 3) HRG binds to integrin α2β1 through a low-affinity interaction that inhibits integrin binding to collagen. This shows that low affinity interactions could be biologically relevant and possibly regulate angiogenesis. 4) The citrullination of collagen, a posttranslational modification reported to occur in rheumatoid arthritis, specifically inhibits the binding of integrin α10β1 and α11β1, but does not affect the binding of α1β1 ja α2β1. On the other hand, the citrullination of isoDGR in fibronectin and RGD in pro-TGF- β:n inhibit integrin binding completely. Citrullination seems to be an inflammation related process and integrin ligands become citrullinated frequently in vivo. This Ph.D. thesis suggests that unconventional interaction mechanisms between integrins and their ligands, such as posttranslational modifications, low affinity interactions, and non-activated integrin conformations, can have an important role in pathological processes. The study of these kinds of integrin-ligand interactions is important for understanding biological phenomena more deeply. The research might also be beneficial for the development of integrin based therapies for treating diseases.

Antiangiogenic And Finasteride Therapies: Responses Of The Prostate Microenvironment In Elderly Mice.

The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice. 90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20mg/kg); SU5416 group: SU5416 (6 mg/kg); TNP-470 group: TNP-470 (15 mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21 days, prostate ventral lobes were collected for morphological, immunohistochemical and Western blotting analyses. The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and endostatin reactivities, and an increase for ER-α, ER-β and VEGF, were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels. The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.

Possible Unconventional Superconductivity In Substituted Bafe2as2 Revealed By Magnetic Pair-breaking Studies.

The possible existence of a sign-changing gap symmetry in BaFe2As2-derived superconductors (SC) has been an exciting topic of research in the last few years. To further investigate this subject we combine Electron Spin Resonance (ESR) and pressure-dependent transport measurements to investigate magnetic pair-breaking effects on BaFe1.9M0.1As2 (M = Mn, Co, Cu, and Ni) single crystals. An ESR signal, indicative of the presence of localized magnetic moments, is observed only for M = Cu and Mn compounds, which display very low SC transition temperature (Tc) and no SC, respectively. From the ESR analysis assuming the absence of bottleneck effects, the microscopic parameters are extracted to show that this reduction of Tc cannot be accounted by the Abrikosov-Gorkov pair-breaking expression for a sign-preserving gap function. Our results reveal an unconventional spin- and pressure-dependent pair-breaking effect and impose strong constraints on the pairing symmetry of these materials.

Prospects For Early Investigational Therapies For Sickle Cell Disease.

Sickle cell disease (SCD) is a genetic disorder characterized by the production of abnormal hemoglobin that polymerizes at low oxygen concentrations, causing the erythrocyte to adopt a sickle-shaped morphology. SCD pathophysiology is extremely complex and can lead to numerous clinical complications, including painful vaso-occlusive crises (VOC), end-organ damage, and a shortened lifespan. An impressive number of investigational drugs are currently in early stages of clinical development with prospects for use either as chronic therapies to reduce VOC frequency and end-organ damage in SCD or for use at the time of VOC onset. Many of these agents have been developed using a pathophysiological-based approach to SCD, targeting one or more of the mechanisms that contribute to the disease process. It is plausible that a multi-drug approach to treating the disease will evolve in the coming years, whereby hydroxyurea (HU) (the only drug currently FDA-approved for SCD) is used in combination with drugs that amplify nitric oxide signaling and/or counteract hemolytic effects, platelet activation and inflammation.

Unconventional neurotransmitters, neurodegeneration and neuroprotection

Neurotransmitters are also involved in functions other than conventional signal transfer between nerve cells, such as development, plasticity, neurodegeneration, and neuroprotection. For example, there is a considerable amount of data indicating developmental roles for the glutamatergic, cholinergic, dopaminergic, GABA-ergic, and ATP/adenosine systems. In this review, we discuss the existing literature on these "new" functions of neurotransmitters in relation to some unconventional neurotransmitters, such as the endocannabinoids and nitric oxide. Data indicating both transcriptional and post-transcriptional modulation of endocannabinoid and nitrinergic systems after neural lesions are discussed in relation to the non-conventional roles of these neurotransmitters. Knowledge of the roles of neurotransmitters in brain functions other than information transfer is critical for a more complete understanding of the functional organization of the brain and to provide more opportunities for the development of therapeutical tools aimed at minimizing neuronal death.

Unconventional metallic behavior and superconductivity in the K-Mo-O system

Transport properties and magnetization measurements of the K(x)MoO(2-delta) (0 <= x <= 0.25) compound are reported. The compound crystallizes in the oxygen deficient MoO(2) monoclinic structure with potassium atoms occupying interstitial positions. An unconventional metallic behavior with power-law temperature dependence is related to a magnetic ordering. Superconducting transition with small volume fraction is also observed near 7 K for a sample with low potassium composition.

DHEA and testosterone therapies in Trypanosoma cruzi-infected rats are associated with thymic changes

The ability of the gonadal hormones to influence diverse immunological functions during the course of several infections has been extensively studied in the latest decades. Testosterone has a suppressive effect on immune response of vertebrates and increases susceptibility toward numerous parasitic diseases. Dehydroepiandrosterone is an abundant steroid hormone secreted by the human adrenal cortex and it is considered potent immune-activator. In this paper, it was examined the effects of DHEA and testosterone supplementation in the thymic atrophy in rats infected with Trypanosoma cruzi, by comparing blood parasitism, thymocyte proliferation, TNF-alpha and IL-12 levels. Our data point in the direction that DHEA treatment triggered enhanced thymocyte proliferation as compared to its infected counterparts and reduced production of TNF-alpha during the acute phase of infection. Oppositely, the lowest values for cells proliferation and IL-12 concentrations were reached in testosterone-supplied animals. The combined treatment testosterone and DHEA improves the effectiveness of the host`s immune response, reducing blood parasites and the immunosuppressive effects of male androgens besides increasing IL-12 concentrations and decreasing TNF-alpha levels. (C) 2010 Elsevier Ltd. All rights reserved.

The use of complementary and alternative therapies by patients with cancer

The aim of this research was to assess the prevalence and predictors of complementary and alternative therapy (CAT) use among cancer patients in Australia. A total of 1492 cancer patients attending nine major public cancer treatment centers in New South Wales, Australia, were asked to complete the Supportive Care Needs Survey. Of the 1354 consenting patients, 888 (65%) returned a completed survey. This article reports the secondary analyses of the survey data, specifically focusing on CAT use. For all cancers, 17.1% of patients were using at least one CAT. The two main demographic characteristics of CAT users were gender and age, where females were more likely to use CAT than males and that CAT use declined as age increased. Time since diagnosis was identified as the only significant clinical predictor of CAT use, where CAT use increased with time until 5 years since diagnosis. Our research shows that herbal treatments and naturopathy are the most popular CAT used by cancer patients (constituting over 30% of all CAT use recorded). The use of CAT among cancer patients is a significant issue in cancer care, especially considering the potential interactions between CAT and conventional medicines. Given that many cancer patients may not be aware of potential risks associated with these interactions it is important that oncologists and others involved in cancer patient care are informed about CAT and its use amongst their patients.

Photosensitizer-Loaded Magnetic Nanoemulsion for Use in Synergic Photodynamic and Magnetohyperthermia Therapies of Neoplastic Cells

In this study a magnetic nanoemulsion (MNE) was developed from a mixture of two components, namely biodegradable surfactants and biocompatible citrate-coated cobalt ferrite-based magnetic fluid, for entrapment of Zn(II)-Phthalocyanine (ZnPc), the latter a classical photosensitizer (PS) species used in photodynamic therapy (PDT) procedures. The sample`s stability was evaluated as a function of time using photocorrelation spectroscopy (PCS) for determination of the average hydrodynamic diameter, diameter dispersion and zeta potential. The ZnPc-loaded magneto nanoemulstion (ZnPc/MNE) formulation was evaluated in vitro assays to access the phototoxicity and the effect of application of AC magnetic fields (magnetohyperthermia damage) after incubation with J774-A1 macrophages cells. Darkness toxicity, phototoxicity and AC magnetic field exposures revealed an enhancement response for combined photodynamic and magnetohyperthermia (MHT) processes, indicating the presence of the synergic effect.

Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score > 2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15-2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.

The effect of oestrogen and alendronate therapies on postmenopausal bone loss around osseointegrated titanium implants

Objectives This study evaluated the influence of oestrogen deficiency and its therapies on bone tissue around osseointegrated implants. Methods Implants were placed in 66 female rats tibiae. The animals were assigned into five groups: control (CTL), sham, ovariectomy (OVX), oestrogen (EST), and alendronate (ALE). While CTL was sacrificed 60 days after implant placement, other groups were subjected to ovariectomy or sham surgery according to group and euthanized after 90 days. Blood and urine samples were collected at sacrifice day for osteocalcin (OCN) and deoxypyridinoline (DPD) quantification. Densitometry of femur and lumbar vertebrae was performed in order to evaluate rats` skeletal impairment. Non-decalcified sections were referred to fluorescent and light microscopy for analyses of mineral apposition rate (MAR), eroded and osteoclastic surfaces, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO). Results Results from the OVX group showed significantly lower bone mineral density (BMD), BIC, BAFO, and MAR, while OCN, deoxipiridinoline, eroded surface and ostecoclastic surface were increased compared with the other groups of the study. ALE reduced OCN and DPD concentrations, MAR, osteoclastic and eroded surfaces, and no difference was in BIC and BAFO relative to SHAM. EST and CTL showed similar results to SHAM for measurements. Conclusions Oestrogen deficiency exerted a negative influence on bone tissue around implants, while oestrogen replacement therapy and alendronate were effective against its effects. Although alendronate therapy maintained the quantity of bone around implants, studies evaluating bone turnover kinetics are warranted. To cite this article:Giro G, Coelho PG, Pereira RMR, Jorgetti V, Marcantonio E Jr, Orrico SRP. The effect of oestrogen and alendronate therapies on postmenopausal bone loss around osseointegrated titanium implants.Clin. Oral Impl. Res. 22, 2011; 259-264.doi: 10.1111/j.1600-0501.2010.01989.x.

Phototherapy Promotes Healing of Chronic Diabetic Leg Ulcers That Failed to Respond to Other Therapies

Objective: We tested the hypothesis that combined 660 and 890 nm LED phototherapy will promote healing of diabetic ulcers that failed to respond to other forms of treatment. Research Design and Methods: A double-blind randomized placebo controlled design was used to study 23 diabetic leg ulcers in two groups of 14 patients. Group one ulcers were cleaned, dressed with 1% silver sulfadiazine cream and treated with ""placebo"" phototherapy (<1.0 J cm(-2)) twice per week, using a Dynatron Solaris 705 (R) device. Group two ulcers were treated similarly but received 3 J cm(-2) dose. Results: At each of 15,30,45,60,75, and 90 days of healing, mean ulcer granulation and healing rates were significantly higher for group two than the ""placebo"" group (P < 0.02). While ""placebo"" treated ulcers worsened during the initial 30 days, group two ulcers healed rapidly; achieving 56% more granulation and 79.2% faster healing by day 30, and maintaining similarly higher rates of granulation and healing over the ""placebo"" group all through. By day 90, 58.3% of group two ulcers had healed fully and 75% had achieved 90-100% healing. In contrast, only one ""placebo"" treated ulcer healed fully by day 90; no other ulcer attained >90% healing. Conclusion: Combined 660 and 890 nm light promotes rapid granulation and healing of diabetic ulcers that failed to respond to other forms of treatment. Lasers Surg. Med. 41:433-441, 2009. (C) 2009 Wiley-Liss, Inc.

Nonsurgical Periodontal Therapy Combined with Laser and Photodynamic Therapies for Periodontal Disease in Immunosuppressed Rats

Background. Periodontal disease is often associated with systemic diseases and is characterized by destruction of the tissues supporting the teeth. Patients using immunosuppressive drugs such as tacrolimus are among those who suffer from tissue destruction. Objective. We sought to evaluate the effects of laser and photodynamic therapies (PDT; nonsurgical) as an adjunct to scaling and rootplaning (SRP) in the treatment of corona-induced periodontitis in rats immunosuppressed with tacrolimus (Prograf). Materials and Methods. The animals were divided into 5 groups. Each groups had 6 rats. Group I, the control group, received only saline solution throughout the study period of 42 days and did not receive periodontal treatment; group II received saline solution and SRP; group III received tacrolimus (1 mg/kg per day) and was treated with SRP; group IV animals were treated identically to group III and then administered laser treatment; and in group V, the animals were treated identically to group III and then administered PDT. Results. Statistical analysis indicated decreased bone loss with the progression of time (P = .035). There was no difference between the bone loss associated with the types of treatment administered to groups I, II, and III (P > .9) or groups IV and V (P > .6). The analysis also indicated that immunosuppression was not a bone loss-determining factor. Conclusion. Laser and PDT therapies were effective as an adjunctive treatment to SRP in reducing bone loss caused by experimental periodontitis induced in animals being treated systemically with tacrolimus.