Tannins as antimicrobial agents: Understanding toxic effects on pathogens.

"Tannins" are compounds that belong to a group of secondary metabolites found in plants. They have a polyphenolic nature and exhibit active actions as first line defenses against invading pathogens. Several studies have demonstrated the multiple activities of tannins, highlighting their effectiveness as broad-spectrum antimicrobial agents. Tannins have reported as antibacterial, antifungal, and antiviral compounds by preventing enzymatic activities and inhibiting the synthesis of nucleic acids. Additionally, tannins primarily strengthen the plant cell wall, making it almost impenetrable to harmful pathogens. Most tannins are synthesized via the phenylpropanoid pathway to become secondary metabolites. Increased uptake of tannins has the potential to provide permanent immunity to subsequent infections by strengthening cell walls and producing antimicrobial compounds. Tannins also demonstrate a synergistic response with other defense-related molecules, such as phytoalexins and pathogenesis-related proteins, including antimicrobial peptides. Studying the mechanisms mediated by tannins on pathogen behaviors would be beneficial in stimulating plant defense against pathogens. This understanding could help explain the occurrence of diseases and outbreaks and enable potential mitigation in both natural and agricultural ecosystems.

Probing nanoliposomes using single particle analytical techniques: effect of excipients, solvents, phase transition and zeta potential.

There has been a steady increase in the interest towards employing nanoliposomes as colloidal drug delivery systems, particularly in the last few years. Their biocompatibility nature along with the possibility of encapsulation of lipid-soluble, water-soluble and amphipathic molecules and compounds are among the advantages of employing these lipidic nanocarriers. A challenge in the successful formulation of nanoliposomal systems is to control the critical physicochemical properties, which impact their in vivo performance, and validating analytical techniques that can adequately characterize these nanostructures. Of particular interest are the chemical composition of nanoliposomes, their phase transition temperature, state of the encapsulated material, encapsulation efficiency, particle size distribution, morphology, internal structure, lamellarity, surface charge, and drug release pattern. These attributes are highly important in revealing the supramolecular arrangement of nanoliposomes and incorporated drugs and ensuring the stability of the formulation as well as consistent drug delivery to target tissues. In this article, we present characterization of nanoliposomal formulations as an example to illustrate identification of key in vitro characteristics of a typical nanotherapeutic agent. Corresponding analytical techniques are discussed within the context of nanoliposome assessment, single particle analysis and ensuring uniform manufacture of therapeutic formulations with batch-to-batch consistency.

Choroid plexus cauterization on treatment of hydranencephaly and maximal hydrocephalus.

INTRODUCTION: The standard treatment for hydranencephaly and maximal hydrocephalus consists of inserting shunts, although complications frequently occur. Choroid plexus cauterization (CPC) is an alternative, but its long-term efficacy and the factors associated with the success and failure of controlling head circumference (HC) are not well defined. OBJECTIVE: This study aims to evaluate the long-term efficacy and factors related to the success rate of CPC in the treatment of hydranencephaly and maximal hydrocephalus. METHOD: Forty-two children with maximal hydrocephalus and hydranencephaly underwent CPC from 2006 to 2014 and were retrospectively evaluated. Children with less than 3 months of follow-up were excluded. The long-term efficacy and success rate of possible variables (i.e., sex, type of malformation, type of surgery performed, treatment hospital, age, and HC at the time of surgery and birth) were evaluated. RESULTS: Thirty-four children were considered for the effectiveness analysis. Treatment was successful in 24 children (70.6%), and failure occurred in 10 children (29.4%). Failure was detected soon after the endoscopic procedure (average 116 days). There was no difference in effectiveness when comparing the age at the moment of surgery (p = 0.473), type of malformation (p = 1), HC at birth (0.699), and HC at the time of surgery (p = 0.648). The surgical death rate was 7.14%. CONCLUSION: Endoscopic CPC was a valid procedure used to treat hydranencephaly and maximal hydrocephaly, and it was effective in 70.6% of cases, with an average follow-up period of 32 months. When failures occurred, they occurred early. None of the analyzed variables interfered with the success of the treatment.

Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional and squamous cell carcinoma of the bladder: effect on survival and bladder preservation.

BACKGROUND: Despite aggressive local therapy, patients with locally advanced bladder cancer have a significant risk of distant metastases. This study evaluated the role of neoadjuvant combination chemotherapy with gemcitabine/cisplatin (GC) in improving the outcome of this group of patients over radical cystectomy alone. PATIENTS AND METHODS: A total of 114 patients with newly diagnosed bladder cancer (T3-4, N0-2, M0) were randomized to radical cystectomy alone or initial 3 cycles of GC, then managed according to response. Patients who achieved complete response completed 6 cycles of GC followed by local radiation therapy (RT) only. If tumors were downstaged to T1, complete transurethral resection was done, followed by 3 cycles of GC and then RT. Patients with partial response underwent radical cystectomy followed by 3 cycles of GC. Patients with stable disease or disease progression underwent radical cystectomy. RESULTS: The overall response rate to GC was 55.1%, and complete response was achieved in 28.6%. The 3-year overall survival (OS) was 51.9% versus 51.2% in the chemotherapy and surgery arms, respectively (P = .399). The 3-year disease-free survival was 31.8% in the chemotherapy arm and 45.1% in the surgery arm (P = .06). Bladder preservation was achieved in 22.5% of patients in the neoadjuvant arm. OS was 78% in responding patients and 100% in patients with complete response. CONCLUSION: Neoadjuvant GC did not improve survival in locally advanced bladder cancer over radical cystectomy alone. However, bladder preservation was feasible, and OS in responding patients was impressive. Therefore, predictive models to select patients are needed. This is the largest prospective study of squamous cell carcinoma and transitional cell carcinoma using neoadjuvant GC.

Scanning tunneling microscopy of cauliflower-like DNA nanostructures synthesised by loop-mediated isothermal amplification.

DNA nanotechnology is a novel approach for synthesis of DNA-based nanostructures. Stem-loops, nanojunctions, sticky-ends and periodic lengths of DNA are the most essential nanostructures in DNA nanofabrications. Loop-mediated isothermal amplification (LAMP) is a powerful technology for repetitive synthesis of double-stranded and cauliflower-like DNAs. The process leads to long and repetitive sequences of DNAs, which are fabricated via loop primers. The authors demonstrate here scanning tunneling micrographs of LAMP-synthesised DNAs deposited on highly ordered pyrolytic graphite. The scans are compared with natural DNAs. Scanning tunneling microscopy (STM) images indicated the creation of periodic long DNAs, stem-looped DNAs and three-way DNA nanojunctions. It is also suggested that such nanomaterials could be promising candidates for use in DNA-based nanodevices.

Detection sensitivity of MRI using ultra-small super paramagnetic iron oxide nano-particles (USPIO) in biological tissues.

Today, by injecting iron oxide based nanoparticles (USPIO) as MRI contrast agents, it is possible to study lymphatic system and some specific tumors and their metastasis. The type of surface coating, and coating characteristics of the nanoparticles are important factors for the biological properties of nanoparticles and their destination target. On the other hand, these properties contribute to different signal intensities. This may confine application of all types of USPIO based contrast agents in routine daily experiments. In this study, the ability of detecting these particles having various sizes and coating properties was evaluated for MRI applications. Signal intensity changes after administration of these particles into tissues have been studied and their detection sensitivity was evaluated using a liver phantom and animal model (rat). IO based nanoparticles of various sizes (8-30 nm) functionalized and coated with various surface polymers such as dextran and starch, amine and hydroxide groups, and bear IO particles were used to investigate the signal changes. The optimized pulse sequences for proper demonstration of lymph nodes using these contrast agents were found (T2* FSPGR protocol with fat suppressions). A detection sensitivity of 98% was achieved in most experiments during applying a proper MR protocol. However, the type of surface coating, and coating characteristics such as thickness were shown to be essential factors for MRI signal intensity in both T1 and T2 protocols.

Renal dysfunction in liver cirrhosis: renal duplex Doppler US vs. scintigraphy for early identification.

A diagnostic tool to detect early renal dysfunction before it becomes irreversible would be useful in cirrhosis. This study was carried out to evaluate the role of Doppler sonography and Tc-99m DTPA renography in the detection of early renal dysfunction in patients with different grades of liver cirrhosis. Renal arteries of 43 patients with cirrhosis and normal renal function tests were compared with 15 age and gender matched normal subjects as a control group using colour Doppler sonography and Tc-99m DTPA scintigraphy. The patients were categorized into three groups, A (14), B (14) and C (15), according to a modified Child's classification that assesses the severity of liver cirrhosis. Doppler results revealed a highly significant increase in both the pulsatility and resistive indices in groups B and C compared with either group A patients or control subjects and in group C compared with group B (P < 0.001) in the main renal arteries as well as in the interlobar and arcuate arteries. Insignificant differences were observed between group A and controls (PI: control 0.96+/-0.08, group A 0.95+/-0.07, group B 1.26+/-0.06, group C 1.48+/-0.06; RI: control 0.57+/-0.02, group A 0.58+/-0.02, group B 0.66+/-0.01, group C 0.72+/-0.02). Abnormal renograms in the form of delayed appearance (34+/-14.6 s), diminished blood flow bilaterally with prolonged secretory (12+/-4.5 min) and excretory phases (> 30 min) and poor response to intravenous frusemide were only observed in group C patients. Radionuclide computed glomerular filtration rate was within the normal range in patients of group A (81+/-9.5 ml/min) and group B (78+/-8.4 ml/min) and reduced only in patients of group C (34+/-14.5 ml/min). Thus Doppler sonography can detect an increase in renal vascular resistance in patients with moderately severe cirrhosis (Child grade B) when renography was normal. We conclude that Doppler sonography can be used for earlier identification of cirrhotic patients with a higher risk of impending renal failure earlier than renography and may also be used to guide therapeutic approaches.

Coronary embolization after balloon angioplasty or thrombolytic therapy: an autopsy study of 32 cases.

OBJECTIVES: This study was undertaken to examine the nature, extent and clinical relevance of coronary embolism after balloon angioplasty or thrombolytic therapy, or both. BACKGROUND: Histopathologic documentation of postinterventional coronary embolization has been reported in only 10 patients from five studies. METHODS: This retrospective autopsy-based study included 32 patients, treated with balloon angioplasty or thrombolysis, or both, who died within 3 weeks of the procedure and underwent autopsy at the Mayo Clinic. Clinical variables included patient age and gender, artery treated, site and type of obstruction, type of intervention, success of the procedure, and postprocedural changes in the electrocardiogram (ECG), cardiac enzymes and hemodynamic status. Histopathologic variables included characteristics of treated plaques, acutely infarcted myocardium and coronary microemboli. Associations between microemboli and clinical and microscopic factors were evaluated by t tests and simple and multiple linear regression. RESULTS: Emboli were observed in 26 (81%) of the 32 patients. Among 83 emboli, 95% were thrombotic or atheromatous. The presence of microemboli was associated statistically with the development of postprocedural infarct extension, new myocardial infarction or new ECG abnormalities. Moreover, the greatest number of microemboli were associated with intervention in the left anterior descending coronary artery, multiple interventional sites, postprocedural medial dissection and plaque rupture or extrusion. CONCLUSIONS: Among patients undergoing balloon angioplasty or thrombolytic therapy who die and undergo autopsy, coronary microemboli occur in a substantial percent. The frequency in survivors is unknown. However, in living patients who develop acute myocardial ischemia or new ECG abnormalities after these interventions, coronary microembolization should be considered a potential cause.

Balloon angioplasty of aortocoronary saphenous vein bypass grafts: a histopathologic study of six grafts from five patients, with emphasis on restenosis and embolic complications.

Among 103 patients undergoing percutaneous transluminal balloon angioplasty of obstructed aortocoronary saphenous vein bypass grafts at the Mayo Clinic, six grafts from 5 patients were available for histopathologic examination. The interval from graft insertion to angioplasty ranged from 5 to 105 months and that from angioplasty to graft excision ranged from 6 h to 24 months. Angioplasty produced intimal fissures in three grafts initially obstructed by intimal fibromuscular proliferation. Healing and restenosis resulted from filling of lacerations with fibrocellular tissue and apparently also from restitution of muscular tone. In two of three grafts initially narrowed by atherosclerosis, balloon angioplasty cause extensive plaque rupture and restenosis resulted from extrusion of plaque debris and secondary luminal thrombosis. In the third graft, angioplasty produced no distinct lesions and late restenosis was due to progressive atherosclerosis of the vein graft. Atheroembolization was observed in both patients with plaque rupture and was associated with reoperation in one and death in the other. In conclusion, the results derived from six saphenous vein bypass grafts subjected to balloon angioplasty indicate that restenosis may result from intimal fibrocellular proliferation, thrombosis, restitution of muscular tone and progressive atherosclerosis. Symptomatic atheroembolization may occur in grafts greater than 1 year old.

Primary unruptured ovarian pregnancy with intrauterine device.

A case of intrafollicular and unruptured ovarian pregnancy associated with intrauterine device which meets the rigid criteria of Spiegelberg (1878) is presented. Clinically, unruptured cases can be confused with ovarian cysts. Intrauterine devices are highly effective for protection against uterine gestation and to a lesser degree against tubal gestation, but they have no effect in preventing ovarian gestation.