Chronic relapsing inflammatory optic neuropathy in a patient with triple antiphospholipid antibody positivity

Neurological Sciences -     

In vitro preliminary study of osteoblast response to surface roughness of titanium discs and topical application of melatonin

Objectives: To observe human osteoblast behavior cultured in vitro on titanium discs (Ti) in relation to surface roughness and melatonin application. Study Design: Human osteoblasts (MG-63) were cultured on 60 Ti6Al4V discs divided into three groups: Group I: discs treated with dual acid etching; Group II dual acid etching and blasting with calcium phosphate particles; Group III (control) machined discs. Surface roughness and topography of the discs were examined with scanning electron microscope (SEM) and confocal laser scanning electron microscope( CLSM). Osteoblast adhesion, proliferation and cell morphology were determined by means of fluorescence microscopy with Image-Pro Plus software and SEM. Results: Group II presented the roughest discs, while the least rough were Group III. Cell adhesion was greatest in Group II. The addition of melatonin improved cell proliferation. Conclusions: 1. Surface treatments (dual acid etching, calcium phosphate impaction) increase surface roughness in comparison with machined titanium. 2. Greater surface roughness tends to favor cell adhesion after 24-hour cell culture. 3. The addition of melatonin tends to favor osteoblast proliferation. Key words:Osteoblasts, titanium, roughness, melatonin, dental implants, osseointegration.     

Chagas disease immunogenetics: elusive markers of disease progression

Introduction: Chagas disease (CD) is caused by a parasitic infection. The disease usually occurs after decades of the primary infection and can involve the myocardium or the digestive system. Of note, around 30% of T. cruzi infected patients develop CD while the other 70% may remain asymptomatic for their entire life. CD is usually observed as familial clustered phenomena. Moreover, individuals with chronic Chagas heart disease (CCHD) usually present a strong, deregulated immune response, which strongly suggests an immunogenetic effect.

Areas covered: In this article we review and discuss the information currently available from the published scientific literature regarding the genetic variants of molecules of the immune system that contribute to the clinical presentation of the disease.

Expert commentary: Of note, the most promissory results are found on the polymorphisms of chemokine receptors, particularly CCR5 and CCR2. Additional investigations are required, particularly with a focus on the genes that regulate the immune system.     

SARS-CoV-2 (COVID-19) en pacientes con algún grado de inmunosupresión

BackgroundIt is not clear whether patients with some degree of immunosuppression have worse outcomes in SARS-CoV-2 infection, compared to healthy people.ObjectiveTo carry out a narrative review of the information available on infection by SARS-CoV-2 in immunosuppressed patients, especially patients with cancer, transplanted, neurological diseases, primary and secondary immunodeficiencies.ResultsPatients with cancer and recent cancer treatment (chemotherapy or surgery) and SARS-CoV-2 infection have a higher risk of worse outcomes. In transplant patients (renal, cardiac and hepatic), with neurological pathologies (multiple sclerosis [MS], neuromyelitis optica [NMODS], myasthenia gravis [MG]), primary immunodeficiencies and infection with human immunodeficiency virus (HIV) in association with immunosuppressants, studies have shown no tendency for worse outcomes.ConclusionGiven the little evidence we have so far, the behaviour of SARS-CoV-2 infection in immunosuppressed patients is unclear, but current studies have not shown worse outcomes, except for patients with cancer.     

A side by side comparison of cytology and biomarkers for bladder cancer detection

PURPOSE: The identification of accurate bladder tumor markers/tests could improve diagnosis, recurrence monitoring and treatment in patients with bladder cancer. In this study we compared the efficacy of the hyaluronic acid (HA)-hyaluronidase (HAase), BTA-Stat (Bard/Bion Diagnostics, Redmond, Washington), Hemastix (Bayer Corp., Elkhart, Indiana) (hematuria detection) and UBC-Rapid (IDL Biotech, Borl?nger, Sweden) tests, and cytology to detect bladder cancer. The HA-HAase test measures urinary HA and HAase levels, BTA-Stat detects complement factor-H and H related protein in urine, the Hemastix hemoglobin dipstick detects hematuria and UBC-Rapid detects cytokeratin 8 and 18 fragments in urine. MATERIALS AND METHODS: A total of 138 urine specimens from 115 patients were collected at University Hospital Hamburg-Eppendorf, including 59 with active bladder cancer and 79 with a history of bladder cancer (73) or with benign genitourinary conditions (6). Specimens were assayed by the HA-HAase test, BTA-Stat, Hemastix (hemoglobin dipstick) and UBC-Rapid. Cystoscopy and histological findings were used to make the clinical diagnosis. Cytology results were available on 92 patients. RESULTS: In a side by side comparison the HA-HAase test, cytology, BTA-Stat, Hemastix and UBC-Rapid had 88.1%, 70.6%, 52.5%, 50.8% and 35.6% sensitivity, and 81%, 81%, 76.7%, 78.2% and 75% specificity, respectively. The accuracy, and negative and positive predictive values of the HA-HAase test were the highest (84.1%, 90.1% and 77.6%), followed by cytology (77.2%, 82.5% and 68.6%), Hemastix (66.4%, 67.8% and 63.8%), BTA-Stat (66.2%, 67.8% and 63.3%) and UBC-Rapid (57.8%, 60% and 52.5%), respectively. CONCLUSIONS:: The HA-HAase test is superior to cytology, BTA-Stat, Hemastix and UBC-Rapid for detecting bladder cancer recurrence. A side-by-side comparison of tumor markers should help identify a marker for monitoring bladder cancer recurrence.     

Enhanced prostate cancer targeting by modified protease sensitive photosensitizer prodrugs

Prodrugs combining macromolecular delivery systems with site-selective drug release represent a powerful strategy to increase selectivity of anticancer agents. We have adapted this strategy to develop new polymeric photosensitizer prodrugs (PPP) sensitive to urokinase-like plasminogen activator (uPA). In these compounds (to be referred to as uPA-PPPs) multiple copies of pheophorbide a are attached to a polymeric carrier via peptide linkers that can be cleaved by uPA, a protease overexpressed in prostate cancer (PCa). uPA-PPPs are non-phototoxic in their native state but become fluorescent and produce singlet oxygen after uPA-mediated activation. In the present work, we studied the influence of side-chain modifications, molecular weight, and overall charge on the photoactivity and pharmacokinetics of uPA-PPPs. An in vitro promising candidate with convertible phototoxicity was then further investigated in vivo. Systemic administration resulted in a selective accumulation and activation of the prodrug in luciferase transfected PC-3 xenografts, resulting in a 4-fold increase in fluorescence emission over time. Irradiation of fluorescent tumors induced immediate tumor cell eradication as shown by whole animal bioluminescence imaging. PDT with uPA-PPP could therefore provide a more selective treatment of localized PCa and reduce side effects associated with current radical treatments.     

Uronate peaks and urinary hyaluronic acid levels correlate with interstitial cystitis severity

PURPOSE: Levels of uronate, a basic component of urothelial glycosaminoglycans, are increased in urine specimens of patients with interstitial cystitis with severe symptoms. In this study we examined the urinary glycosaminoglycan profile and correlated the profile and urinary hyaluronic acid (a glycosaminoglycan) levels with symptom severity. MATERIALS AND METHODS: Urine specimens and completed O'Leary-Sant interstitial cystitis symptom and problem indexes questionnaires were obtained from 29 patients with interstitial cystitis, 14 normal individuals, and 14 patients with other benign pelvic and bladder conditions. Patients with interstitial cystitis were divided into group 1-1 or both indexes less than 50% maximum score, and group 2-both indexes 50% of maximum score or greater. All patients met the National Institutes of Diabetes and Digestive and Kidney Diseases criteria except regarding glomerulation. In a followup study 30 urine specimens were collected from 8 patients with interstitial cystitis and from 4 normal individuals during 12 months. The urinary glycosaminoglycan profile was determined by gel filtration chromatography. Glycosaminoglycan peaks were analyzed by polyacrylamide gel electrophoresis. Urinary hyaluronic acid levels were determined by the hyaluronic acid test. RESULTS: Group 2 urine specimens contained 3 uronate peaks, whereas urine specimens from normal individuals and patients in group 1 contained 1 or 2 peaks. Peak 1 consisted of macromolecular glycosaminoglycans whereas peaks 2 and 3 contained oligosaccharides. Urinary hyaluronic acid levels were 3 to 4-fold increased in group 2. Glycosaminoglycan profile and hyaluronic acid levels detected interstitial cystitis severity with 83% sensitivity, and 89.7% and 74.4% specificity, respectively. Interstitial cystitis urothelial cells/tissues also over expressed hyaluronic acid synthase 1 (which synthesizes hyaluronic acid) compared to normal urothelial cells/tissues. In the followup study urinary uronate levels, glycosaminoglycan profile and hyaluronic acid levels detected patients with severe symptoms with 73% sensitivity and 87% to 94% specificity. In both studies uronate, glycosaminoglycan profile and hyaluronic acid levels significantly correlated with interstitial cystitis severity (p <0.001). CONCLUSIONS: Urinary glycosaminoglycan profile, uronate content and hyaluronic acid levels are potentially useful markers for monitoring interstitial cystitis severity, and are likely to be involved in interstitial cystitis pathophysiology.     

Cost-effectiveness of biological therapy compared with methotrexate in the treatment for rheumatoid arthritis in Colombia

The objectives of the study are to develop a cost-effectiveness model comparing biological therapy (BT) with methotrexate (MTX) alone, in the treatment for rheumatoid arthritis (RA), combining clinical and quality-of-life data from international trials with local costs and local epidemiological data. We designed a six-month cycle Markov model with five functional states, based on Health Assessment Questionnaire, with patients initiating treatment in any of the predefined states, based on a sample of 150 local RA patients. Simulations ran for 10 and 20 years, and for the whole life span. Utilities, in quality-adjusted life years (QALY), were taken from international literature. Discount rate was 3 % for costs and utilities. We calculated direct and indirect costs using a combination of international and local data. Results are presented as incremental cost-effectiveness ratios (ICER). ICERs in euros per QALY were €143,072 for 10 years; €139,332 for 20 years; and €137,712 for the whole life span. Total costs with MTX were lower than with BT, despite higher out of pocket, productivity, and complication costs. Under conventional thresholds, and for the “average” RA patient, BT would not be cost-effective in Colombia. BT compared to MTX provides more QALYs, but at a high cost. When ICERs were estimated for Colombia, BT would not be cost-effective. We propose different thresholds for different conditions, perhaps prioritizing chronic diseases that lead to disability.