Appendicolith classification: physical and chemical properties of appendicoliths in patients with CT diagnosed acute appendicitis - a prospective cohort study.

OBJECTIVE: Appendicoliths are associated with a more complicated course of acute appendicitis and failure of non-operative treatment. We aimed to update the appendicolith classification originally described in 1966 and to assess the association of appendicolith characteristics with appendicitis severity. DESIGN: This prospective predefined MAPPAC-trial (ClinicalTrials.gov NCT03257423) substudy included patients with CT diagnosed appendicitis presenting with an appendicolith. CT visible appendicoliths were harvested at surgery, measured and characterised by morphological examination complemented with micro-CT and micro-X-ray fluorescence spectroscopy. Patients were categorised into two groups: appendicolith appendicitis without other complications and appendicolith appendicitis with complications (appendiceal gangrene, perforation and/or abscess). The association of appendicolith classification and characteristics with appendicitis severity was evaluated. RESULTS: Of 78 patients with a CT appendicolith, 41 appendicoliths were collected and classified based on the degree of hardness into three classes. The hardest appendicoliths (class 3) were less common (19.5%) presenting with a stone-hard outer layer and concentrically layered inner structure around a core. The layered inner structure was also observed in class 2 appendicoliths, but was absent in soft, class 1 appendicoliths. Appendicolith hardness or measures (maximum length, diameter and weight) were not associated with appendicitis severity. The spatial distribution of the main inorganic elements of calcium and phosphorus varied within most appendicoliths. CONCLUSION: This updated classification confirms categorisation of CT visible appendicoliths into three classes based on their physical and chemical characteristics. The data on clinical and aetiopathological characteristics of appendicoliths is scarce and using this systematic classification would add to this understanding.

Reaction mechanisms of flavins and flavoproteins from an electronic-structure perspective / Mecanismos de reação de flavinas e flavoproteínas por uma perspectiva de estrutura eletrônica

Proteins equipped with flavin adenine dinucleotides (FAD) or flavin mononucleotides (FMN) are named flavoproteins and constitute about 1% of all existing proteins. They catalyze redox, acid-base and photochemical reactions in a variety of biochemical phenomena that goes from energy metabolism to DNA repair and light sensing. The versatility observed in flavoproteins is ultimately a balance of flavin intrinsic properties modulated by a protein environment. This thesis aims to investigate how flavoproteins work by systematic evaluating flavin properties and reactivity. In particular, the mechanism of fumarate reduction by the flavoenzyme fumarate reductase Fcc3 was determined. Electronic-structure calculations were used for this task based on rigorous calibration with experimental data and error assessment. Flavin properties at chemical accuracy were obtained with single reference coupled-cluster CCSD(T) calculations at the complete basis set limit. Density functional theory was demonstrated an excellent alternative with lower computational costs and slightly less accuracy. Flavin protonation and tautomerism were shown to be important modulators of flavin properties and reactivity, with the possibility of various tautomers existing at neutral pH. Regarding flavin redox properties, an analysis based on multiconfigurational wave function weights was proposed for categorizing flavin redox reactions as hydride or hydrogen-atom transfers. This analysis is an upgrade over traditional partial charges methods and can be applied not only to flavin reactions but to any protoncoupled electron transfer. In the investigation of the enzymatic mechanism of fumarate reduction, the reaction was determined as a nucleophilic addition by hydride transfer with carbanion formation. Fumarate reductase employs electrostatic catalysis in contrast to previous proposals of substrate straining and general-acid catalysis. Also, hydride transfer was shown to be vibronically adiabatic with low tunneling contribution. These findings give new insights into the mechanisms of fumarate reductases and provide a framework for future computational studies of flavoproteins in general. The analyses and benchmark studies presented can be used to build better models of properties and reactivity of flavins and flavoproteins

Proteínas equipadas com dinucleotídeos de flavina-adenina (FAD) e mononucleotídeos de flavina (FMN) são chamadas flavoproteínas e constituem cerca de 1% de todas as proteínas existentes. Elas catalisam reações redox, ácido-base e fotoquímicas numa variedade de fenômenos bioquímicos que vão desde o metabolismo energético até reparo de DNA e captação de luz. A versatilidade observada em flavoproteínas é em última instância um balanço das propriedades intrínsecas de flavinas moduladas por um ambiente proteico. Esta tese busca investigar como flavoproteínas funcionam através de avaliações sistemáticas de propriedades e reatividade de flavinas. Em particular, o mecanismo de redução de fumarato pela flavoenzima fumarato redutase Fcc3 foi determinado. Cálculos de estrutura eletrônica foram usados para esta tarefa com base em rigorosa calibração com dados experimentais e avaliação de erros. As propriedades de flavinas foram determinadas com acurácia química com cálculos monoconfiguracionais de coupled-cluster CCSD(T) no limite de conjunto base completo. A teoria do funcional da densidade mostrou-se uma alternativa excelente com menor custo computacional e um pouco menos de acurácia. Protonação e tautomerismo de flavinas mostraram-se moduladores importantes de suas propriedades e reatividade, com a possibilidade de vários tautômeros existirem em pH neutro. Em relação às propriedades redox de flavinas, uma análise baseada nos pesos de funções de onda multiconfiguracionais foi proposta para categorizar as reações redox de flavinas como transferências de hidreto ou hidrogênio. Esta análise é uma melhoria em relação aos métodos tradicionais de cargas parciais e pode ser aplicada não apenas para reações de flavinas mas para qualquer transferência de próton acoplada a elétrons. Na investigação do mecanismo enzimático de redução de fumarato, a reação foi designada como uma adição nucleofílica por transferência de hidreto e formação de carbânion. A fumarato redutase usa catálise eletrostática diferentemente de prospostas anteriores envolvendo distorção do substrato e catálise ácida geral. Além disso, a transferência de hidreto mostrou-se vibronicamente adiabática com pouca contribuição de tunelamento. Estas descobertas abrem novas perspectivas sobre os mecanismos de fumarato redutases e fornecem uma base para estudos computacionais futuros sobre flavoproteínas em geral. As análises e estudos comparativos apresentados podem ser usados para construir melhores modelos para propriedades e reatividade de flavinas e flavoproteínas

Exploration of the Potential Mechanism of Calculus Bovis in Treatment of Primary Liver Cancer by Network Pharmacology.

AIM AND OBJECTIVE: Calculus Bovis (CB) has been employed to treat diseases for a long time. It has been identified to play significant anti-inflammatory and anti-tumor roles. However, the mechanism of treating primary liver cancer (PLC) remains to be revealed. This study aims to clarify the molecules and mechanisms of CB in treating PLC. MATERIALS AND METHODS: After oral bioavailability (OB) and drug-likeness (DL) screening, 15 small molecules were identified as the potential ingredients against PLC. Following this, related targets network constructions and pathways were applied to clarify the mechanism of CB in treating PLC. An in vitro experiment was carried out to identify the function of CB in treating PLC. RESULTS: Eleven compounds of CB were identified that play an anti-PLC role, including oleanolic acid, ergosterol, ursolic acid, etc. The potential targets which were observed include IL6, MAPK-8, VEGFA, Caspase-3, etc. Further analysis showed that the mechanism of CB in the treatment of PLC involved apoptosis-related pathways and immune-related pathways. CONCLUSION: In summary, the current study combines network pharmacology and in vitro experiments to reveal the mechanism of CB against PLC. We concluded that 11 ingredients of CB have an anti-PLC effect. Furthermore, CB plays a key role in treating PLC mainly by apoptosisrelated pathways and immune-related pathways. Our experiment verifies that CB promotes the apoptosis of SMMC-7721.

Vaginal Calculus in a Woman With Mixed Urinary Incontinence and Vaginal Mesh Exposure.

Vaginal calculi are extremely rare and are most commonly encountered in the setting of an urethrovaginal or vesicovaginal fistula. We present a case of a 72-year-old woman with mixed urinary incontinence and vaginal mesh exposure incidentally found to have a large vaginal calculus. We removed the calculus surgically and analyzed the components. Results demonstrated the presence of ammonium-magnesium phosphate hexahydrate and carbonate apatite.

[Simultaneous determination of seven residual solvents in bovis calculus artifactus by headspace gas chromatography].

A headspace gas chromatography (HS-GC) method was developed for the simultaneous determination of seven residual solvents (petroleum ether (60-90 degrees C), acetone, ethyl acetate, methanol, methylene chloride, ethanol and butyl acetate) in bovis calculus artifactus. The DB-WAX capillary column and flame ionization detector (FID) were used for the separation and detection of the residual solvents, and the internal standard method was used for the quantification. The chromatographic conditions, such as equilibrium temperature and equilibrium time, were optimized. Under the optimized conditions, all of the seven residual solvents showed good linear relationships with good correlation coefficients (not less than 0.999 3) in the prescribed concentration range. At three spiked levels, the recoveries for the seven residual solvents were 94.7%-105.2% with the relative standard deviations (RSDs) less than 3.5%. The limits of detection (LODs) of the method were 0.43-5.23 mg/L, and the limits of quantification (LOQs) were 1.25-16.67 mg/L. The method is simple, rapid, sensitive and accurate, and is suitable for the simultaneous determination of the seven residual solvents in bovis calculus artifactus.

Predicting urinary stone composition based on single-energy noncontrast computed tomography: the challenge of cystine.

OBJECTIVE: To study several measurements from a single-energy noncontrast computed tomography (NCCT) that may distinguish calcium oxalate, uric acid, and cystine stones. METHODS: Patients with pure urinary stones who had at least 1 single-energy NCCT before the stone composition analysis from January 2008 to December 2012 were enrolled in this study. The analyzed data comprised stone size, volume, core Hounsfield unit (HU), periphery HU, absolute and relative HU differences between core and periphery, and HU density. After these measurements, an NCCT bone window was subjectively evaluated to study the homogeneity of each stone from core to periphery. The Spearman correlation test was used to determine the correlation between HU values and stone size and volume for each group. RESULTS: A total of 113 patients were found with pure urinary stones who also had a corresponding NCCT. There were 36, 47, and 30 patients in the calcium oxalate, uric acid, and cystine groups, respectively. The core HU, periphery HU, absolute and relative HU differences, and HU density were significantly different among the 3 groups (P<.001). Stone size and volume had a positive correlation with core and periphery HUs only for calcium oxalate and cystine stones. The subjective evaluation of the urinary calculi revealed a different pattern for each stone composition. CONCLUSION: Single-energy NCCT may predict calcium oxalate stones with a high degree of accuracy. There is an overlap in radiographic profiles of cystine and uric acid stones, making a definitive differentiation more challenging.

Timing of intra-lesion shaving for surgical treatment of chronic tophus.

OBJECTIVES: Gouty arthritis results from the deposition of monosodium urate crystals in synovial spaces. The literature shows that a tophus may require surgical treatment to improve cosmesis or function, to alleviate pain, to eradicate sinus drainage or to remove large urate deposits. However, forceful curettage to remove tophus particles embedded in the thin attenuated skin flap may compromise blood circulation and cause other complications. This series presents the experience of the authors in performing intra-lesion shaving during the surgical treatment of tophus patients. METHODS: This study analysed 147 surgical procedures performed in 108 patients with chronic tophus at a single hospital during November 2000 to July 2010. All patients underwent a soft-tissue shaver-assisted intra-lesion excavating technique developed by the authors. Bimanual palpation of the skin was performed to avoid trauma to the skin envelope. The shaving technique proved to be a simple and efficient method of reducing the total urate burden in the body. RESULTS: Compared to conventional surgical treatment, the shaver technique is a safer and more effective option for treating tophus lesions. In this series, wound cultures were positive in 18.4% of operations. Patients with positive wound cultures and chronic renal impairment had significantly longer hospital stays compared to patients with negative wound cultures and patients without chronic renal impairment (P=0.0019 and P=0.0045, respectively); patients with C-reactive protein (CRP)<5 mg l(-1) and white blood cell (WBC) count<10,000 µl(-1) had significantly shorter hospital stays compared to patients with CRP>5 mg l(-1) and WBC>10,000 µl(-1) (P=0.0002 and 0.006, respectively). The upper extremities group and the upper-lower extremities group had significantly shorter hospital stays compared to the lower extremities group (P=0.001 and P=0.0014, respectively). CONCLUSIONS: Medical treatment to control hyperuricaemia is important for reducing the risk of an acute attack of tophus formation. However, the data in this series show that surgery should be performed before the skin becomes ulcerated and before the tophus mass becomes infected. The proposed shaver technique markedly reduces tophus of the extremities with minimal surgical complications.

Prostatic stones: evidence of a specific chemistry related to infection and presence of bacterial imprints.

Prostatic stones are a common condition in older men in industrialized countries. However, aging appears not to be the unique pathogenesis of these calcifications. Our morpho-constitutional investigation of 23 stone samples suggested that infection has a significant role in the lithogenic process of prostate calcifications, even without detection of infection by clinical investigation. Most stones (83%) showed bacterial imprints and/or chemical composition, suggestive of a long-term infection process. Chronic infection may induce persistent inflammation of the tissue and secondarily, a cancerization process within a few years. Thus, the discovery of prostate calcifications by computerized tomodensitometry, for example, might warrant further investigation and management to search for chronic infection of the prostate gland.

Application of mineralogical techniques in the study of human lithiasis.

The authors review the mineralogical methods and techniques of analyzing calculi, stony concretions in the body. They discuss the main types of kidney stones (prostate, testicular, salivary, and bile) and the different diagnostic methods in mineralogy. By applying the techniques of optical microscopy and electron microscopy, they describe the different characteristics of human stones, based on extensive experience as evidenced by their numerous studies.

Lithiazis in the periurethral gland of a woman.

We present a very rare case of stone formation in the periurethral gland of a 49-year-old woman who was referred to our hospital with suspicion of a malignant or granulomatous soft-tissue lesion in the paraurethral area. The lesion was excised and the histopathological examination revealed cystic dilatation and squamous metaplasia in the lining of the glandular structure and surrounding lymphocyte infiltration. The scanning electron microscope examination of the stone revealed egg shell-like stratified concentric calcifications. The chemical composition revealed by the X-ray diffraction technique was a mixture of calcium oxalate and phosphate similar both at the outer and inner layers.

Bacterial and mucopeptide concretions of the lacrimal drainage system: an analysis of 30 cases.

PURPOSE: To demonstrate the histopathologic characteristics of different types of lacrimal drainage system concretions with clinical correlations. METHODS: Thirty lacrimal drainage system concretions submitted to the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary over a 2-year period were reviewed. Concretions were studied in detail using their histopathologic staining features as revealed with hematoxylin and eosin, Gomori methenamine silver, periodic acid-Schiff, iron stain, and Brown-Hopps tissue gram stain. A separate retrospective chart review was conducted for each patient to identify any clinical correlations. RESULTS: Two major forms of concretions were identified histopathologically: mucopeptide (7) and bacterial (20). Mucopeptide concretions were found exclusively within the lacrimal sac, while bacterial concretions were found chiefly in the canaliculus. A third category of "mixed" concretions with substantial mucopeptide and bacterial characteristics comprised 3 specimens. Bacterial concretions consisted of large matted masses of filamentous, presumed Actinomyces organisms that were easily identified with the Grocott's methenamine silver stain; they were frequently cocolonized at their edges with coccal bacterial forms. Mucopeptide concretions were generally devoid of cellular elements and were composed of broad bland whorls of diffusely eosinophilic, acellular, periodic acid-Schiff-positive material punctuated by lacunae. They were often cocolonized by small numbers of bacterial cocci and occasional fungi. Culture results disclosed low virulence species. All 3 types of concretions predominated in women. Patients with bacterial concretions frequently had dry eye symptoms. CONCLUSIONS: The 2 major types of lacrimal system concretions differ in their primary location and histopathologic composition. Further characterization may lead to an understanding of the mechanisms for their formation. Mucopeptide concretion is more appropriate than terms such as "dacryolith" and "mucolith," and bacterial concretion is a more appropriate term than "canaliculith," because of the absence of significant calcium or stone-like density in these masses.

Bilateral very large calcium oxalate stones in the seminal vesicles: case report and literature review.

A 29-year-old man with hypospadias and bilateral undescended testicles presented with recurrent attacks of lower urinary tract infections and painful ejaculation. He was diagnosed to have very large bilateral seminal vesicle stones. The pelvis X-ray showed two radio-densities located in the pelvis with symmetrical appearance while Ultrasound showed them as echogenic structures with posterior acoustic shadowing. In magnetic resonance imaging (MRI) of the pelvis they appeared hypointense in both T1-weighted and T2-weighted images while pelvic computed tomography scan (CT scan) showed bilateral huge stones in the seminal vesicles. The stones were extracted by open surgery through the bladder after transurethral excision of the ejaculatory ducts. Here, we report the first case of bilateral, large, heart-shaped, calcium oxalate monohydrate of seminal vesicle caliculi with brief literature review.

Preliminary feasibility study of FTIR microscopic mapping system for the rapid detection of the composited components of prostatic calculi.

Awareness of the chemical composition of prostatic calculi is of great importance for pathogenesis of prostatic lithiasis, the feasibility of FTIR microspectroscopic mapping system used for rapidly screening and detecting the real composited components of prostatic calculi in a short time was initially evaluated. Prostatic calculi were retrieved during transurethral resection of the prostate from nine patients diagnosed having benign prostatic hyperplasia with lower urinary tract symptoms. The level of serum prostatic-specific antigen was within 0-12.63 ng/ml. The calculi samples were examined and compared using FTIR microspectroscopic mapping system, or the traditional FTIR and Raman microspectroscopies. The traditional FTIR microspectroscopic results indicate that nine calculi samples mainly consisted of carbonated HA (hydroxyapatite), but calcium oxalate (undifferentiated) might be also detected in some samples. However, Raman spectral results could detect three components, HA, COM (calcium oxalate monohydrate) or COD (calcium oxalate dihydrate) separated in nine samples. Different compositions in the prostatic calculi were obtained by both spectroscopic detections with manual single-point random analysis implying that both manually traditional methods were failed to provide the real chemical composition of the prostatic calculi in a short time. The FTIR microscopic mapping system via point-by-point mapping analysis evidenced that it could rapidly detect all the complicated components distributed within the prostatic calculi rather than uncertain components detected by traditional FTIR or Raman microspectroscopy. More studies should be carried out in future. This preliminary result suggests that the FTIR mapping better characterizes the stone composition over single-point FTIR and Raman microscopic analysis in prostatic calculi.

[Prostatic calculi: silent stones]. / Litiasis prostática: cálculos silentes.

INTRODUCTION AND OBJECTIVES: Prostate stones are frequently encountered during transurethral resection of the prostate in urology practice. We aimed to demonstrate the physical and chemical properties of prostate stones. We also aimed to determine possible relationship between inflammation of prostate gland and prostate stones. METHODS: The consecutive patients (excluding subjects with PSA>or=4ng/ml and urolithiasis), who underwent TURP operation and who were observed to have prostatic calculi during TURP, were included in the study. The prostatic stones obtained from each patient during TURP were analysed for chemical composition and observed under electron microscopy (SEM) for structure and surface morphology. The pathological specimens were assessed by the uropathologist for the final diagnosis and existence and degree of inflammation. RESULTS: Five patients were included in the study. From each patient at least three (range 3-8) samples of stones (diameter varying from 1mm up to 5mm) were obtained. The stones were made of mixed composition of calcium phosphate and calcium carbonate. The stones were found to have lobular surface made up of small spheres under SEM. Histopathological examination of the TURP specimens revealed being prostatic hyperplasia accompanied with inflammation of mild to severe degree. CONCLUSIONS: Prostatic stones are concentrically precipitated calcium stones within the prostatic ductuli with granular grape like morphology. Histopathological inflammation seems to be associated with these prostatic calculi.

Evaluation of trends in urolith composition and characteristics of dogs with urolithiasis: 25,499 cases (1985-2006).

OBJECTIVE: To evaluate trends in urolith composition and urolithiasis in dogs during the past 21 years. DESIGN: Retrospective case series. SAMPLE POPULATION: 25,499 uroliths and the dogs from which they were obtained. PROCEDURES: Database of the Gerald V. Ling Urinary Stone Analysis Laboratory was searched from January 1985 through December 2006. All uroliths from dogs and the accompanying submission forms were evaluated. Age, sex, breed, and urolith location were recorded. RESULTS: Minerals identified in uroliths included struvite, calcium oxalate (CaOx), urate, apatite, brushite, cystine, silica, potassium magnesium pyrophosphate, sulfa drug, xanthine, and newberyite. Although more struvite-containing uroliths were submitted during this period, a significant decrease in the proportion of struvite-containing uroliths submitted as a percentage of all uroliths submitted was detected. Also, a significant increase in the proportion of CaOx-containing uroliths submitted over time was detected. There was a significant nonlinear decrease in submission of urate-, silica-, and cystine-containing uroliths. The CaOx-, cystine-, and silica-containing uroliths were obtained significantly more often from male dogs; struvite- and urate-containing uroliths were obtained significantly more often from female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: An increase in the proportion of CaOx uroliths submitted over time was detected. Reasons for long-term changes in this trend were likely multifactorial and could have included alterations in diet formulations and water consumption and possibly the fact that people favor ownership of breeds more prone to developing CaOx-containing uroliths. The decrease in metabolic uroliths could have been related to better breeding practices and increased awareness of results of genetic studies.

Vaginal stones in a 5-year-old girl: a novel approach of removal.

BACKGROUND: Primary vaginal stones in children are extremely rare and removal can be difficult. We describe a procedure for safe extraction of vaginal stones. CASE: A 5-year-old, wheelchair-bound girl was referred to the urologic department with recurrent febrile urinary tract infection. Diagnostics of the kidneys showed no abnormalities. The bladder appeared to contain two stones. On urethro-cystoscopy no stones were seen. Vaginoscopy identified vaginal stones. After 4 weeks of estrogen treatment, a second procedure via vaginal introduction of a nephroscope in combination with an ultrasonic device, effectively disintegrated the stones. SUMMARY AND CONCLUSION: We recommend the use of a nephroscope in visualizing the vagina and cervix and facilitating instrumentation in prepubertal girls.

Mechanism of formation of concentrically laminated spherules: implication to Randall's plaque and stone formation.

We report on the formation of calcium phosphate multi-laminated spherules via a polymer-induced liquid-like precursor (PILP) process. In this non-classical crystallization route, the precipitation of liquid-like amorphous calcium phosphate (ACP) particles is promoted using anionic polypeptide additives, and these droplets coalesce to form globules that later crystallize into spherulites. During crystallization of the amorphous globules, the polymer additive, as well as the waters of hydration, is excluded ahead of the crystallization front, but some polymer becomes entrapped within diffusion-limited zones. This results in the formation of concentric laminations with layers of variable density from organic-rich inclusions. The striking resemblance of these spherules with the crystals of the Randall's plaque and other laminated stones suggests that such biological structures may form via an amorphous precursor process as well. Given the organic-rich environment present in the urinary tract, one might expect a large amount of organic materials to become entrapped within the stratified zones of a forming stone during this type of solidification and transformation process.