Assessment of Unicuspid Aortic Valve Stenosis Using Multimodality Imaging, X-ray Radiography and Raman Analysis.

Unicuspid aortic valve (UAV) is an extremely rare form of congenital cardiac malformation, leading to aortic stenosis (AS), aortic regurgitation (AR), or both. We report the case of a 55-year-old man with unicommissural UAV associated with severe AS and mild AR using different multimodality imaging approaches. The excised UAV isolated after aortic valve replacement exhibited an eccentric "teardrop" opening with a slit-shaped unicommissural structure. Raman spectroscopic results indicated that 3 unevenly distributed components were deposited on the surface of the UAV, in which calcium hydroxyapatite and type-B carbonate apatite were the predominate components deposited on the surface, leading to severe AS formation.

Echocardiographic manifestations and chemical composition of stenotic bicuspid aortic valves.

Bicuspid aortic valve (BAV) is an inherited form of heart disease with only two aortic valve leaflets via a disorder of cardiac valvulogenesis. We investigated the in vivo echocardiographic features of cardiac morphology in patients with BAV and the ex vivo compositional components of all the excised BAV leaflets isolated from BAV patients. Three BAV patients were randomly selected. All patients underwent 2D transthoracic echocardiography (TTE) with a Doppler ultrasound tool. The compositional components of each respective BAV leaflet for all the excised BAVs were determined by a portable fiber-optic Raman spectroscopy. Preoperative TTE revealed the thickened and calcified BAV leaflets, and stenotic aortic flow for all BAV patients. These BAV patients exhibited severe aortic stenosis (AS) by the lower values of aortic valve area (AVA) index. One patient showed a more significant left ventricle hypertrophy, whereas two patients exhibited a significant aortic regurgitation (AR). In addition, three different Raman spectral patterns were summed up from 121 randomized Raman determinations for all the excised BAV leaflets. The main calcified deposition in each BAV leaflet was formed by large amounts of calcium hydroxyapatite and type-B carbonate apatite (Raman bands at 960 and 1070 cm-1). The calcified BAV leaflets were composed of different compositional components such as calcium hydroxyapatite, type-B carbonate apatite, lipids, proteins, cholesterol and ß-carotene. The rare NL subtype of type 1 BAV morphotype was found in one patient, but two patients had the purely BAV morphotype with two equal-sized leaflets.

One-step Real-time Food Quality Analysis by Simultaneous DSC-FTIR Microspectroscopy.

This review discusses an analytical technique that combines differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy, which simulates the accelerated stability test and detects decomposition products simultaneously in real time. We show that the DSC-FTIR technique is a fast, simple and powerful analytical tool with applications in food sciences. This technique has been applied successfully to the simultaneous investigation of: encapsulated squid oil stability; the dehydration and intramolecular condensation of sweetener (aspartame); the dehydration, rehydration and solidification of trehalose; and online monitoring of the Maillard reaction for glucose (Glc)/asparagine (Asn) in the solid state. This technique delivers rapid and appropriate interpretations with food science applications.

Dual-Energy Computed Tomography Gemstone Spectral Imaging: A Novel Technique to Determine Human Cardiac Calculus Composition.

OBJECTIVE: Understanding the chemical composition of any calculus in different human organs is essential for choosing the best treatment strategy for patients. The purpose of this study was to assess the capability of determining the chemical composition of a human cardiac calculus using gemstone spectral imaging (GSI) mode on a single-source dual-energy computed tomography (DECT) in vitro. METHODS: The cardiac calculus was directly scanned on the Discovery CT750 HD FREEdom Edition using GSI mode, in vitro. A portable fiber-optic Raman spectroscopy was also applied to verify the quantitative accuracy of the DECT measurements. RESULTS: The results of spectral DECT measurements indicate that effective Z values in 3 designated positions located in this calculus were 15.02 to 15.47, which are close to values of 15.74 to 15.86, corresponding to the effective Z values of calcium apatite and hydroxyapatite. The Raman spectral data were also reflected by the predominant Raman peak at 960 cm for hydroxyapatite and the minor peak at 875 cm for calcium apatite. CONCLUSIONS: A potential single-source DECT with GSI mode was first used to examine the morphological characteristics and chemical compositions of a giant human cardiac calculus, in vitro. The CT results were consistent with the Raman spectral data, suggesting that spectral CT imaging techniques could be accurately used to diagnose and characterize the compositional materials in the cardiac calculus.

Biochemical and molecular aspects of spectral diagnosis in calcinosis cutis.

Calcinosis cutis (CC) is a type of calcinosis wherein insoluble compounds or salts deposited on the skin. Clinical diagnosis of CC is usually achieved through time consuming histopathological or immunohistochemical procedures, but it can only be empirically identified by experienced practitioners. The use of advanced vibrational spectroscopy has been recently shown to have great potential as a diagnostic technique for various diseased tissues because it analyses the chemical composition of diseased tissue rather than its anatomy and predicts disease progression. This review article includes a summary of the application of Fourier transform infrared (FT-IR) and Raman spectroscopic or microspectroscopic analysis for the rapid diagnosis and identification of the chemical composition of skin calcified deposits in patients with various CC symptoms. Both advanced techniques not only can detect the types of insoluble salts such as calcium phosphate, calcium carbonate, and monosodium urate, and ß-carotene in the calcified deposits of human skin tissue but also can directly differentiate the carbonate substitution in the apatite structure of the skin calcified deposits. In particular, the combination of both vibrational techniques may provide complementary information to simultaneously assess the intact components of the calcified deposits. In the future, both FT-IR and Raman vibrational microspectroscopic techniques will become available tools to support the standard test techniques currently used in some clinical diagnoses. Molecular spectroscopy technique is rapidly changing disease diagnosis and management.

An overview of famotidine polymorphs: solid-state characteristics, thermodynamics, polymorphic transformation and quality control.

Crystal polymorphism of pharmaceuticals has well-known profound effects on the physical, chemical, and pharmaceutical properties of drugs, which can result in changes in the solubility, stability, dissolution, bioavailability, and efficacy of drugs. In this review article, famotidine (FAM), which has a well-known trade name of Pepcid®, was selected as a model drug. Although FAM has three polymorphs (forms A, B and C), forms A and B have been commonly discussed. The active pharmaceutical ingredient (API) in the commercial version of FAM is the metastable form B. FAM has been a concern of FDA because of the physical properties, solubilities, bioavailabilities, or bioequivalencies of the different polymorphic forms. In addition, a patent infringement suit of FAM polymorph had been made sound legal arguments in the pharmaceutical market. We review the solid-state characteristics, thermodynamics, polymorphic transformation, and quality control of FAM in drug products. In particular, pharmaceutical processes, such as grinding, compression, and heating temperature have a significant effect on the polymorphic transformation of FAM. Moreover, environmental humidity and residual water content should be well controlled to prevent polymorphic transformation of FAM during pharmaceutical processing. Several thermal and spectroscopic analytical techniques used for qualitative and quantitative determinations of polymorphic transformation of FAM after different treatments or quality control of FAM in the commercial tablets before and after the expiration dates have been discussed.

Application of scanning electron microscopy and X-ray microanalysis: FE-SEM, ESEM-EDS, and EDS mapping for studying the characteristics of topographical microstructure and elemental mapping of human cardiac calcified deposition.

To explore the pathogenic mineral formation in a huge cardiolith isolated from the left heart atrium of an 80-year-old male patient, field emission scanning electron microscopy (FE-SEM) was used to analyze the topographic microstructure and perform elemental mapping in a cross-section of the cardiac calcified deposit after dissection. Environmental SEM equipped with an energy dispersive X-ray spectrometer (EDS) was also used to investigate the composition and spatial distribution of elements in the cross-section, and fiberoptic Raman spectroscopy was used to reidentify the chemical composition of designated positions. The results indicated that calcium hydroxyapatite and cholesterol were the main components of the cardiac calculus. The plate-like structures of calcium hydroxyapatite were unevenly spread over the cholesterol of the cardiac calculus. The calcium hydroxyapatite-rich area exhibited higher amounts of C, O, P, and Ca elements as well as trace amounts of N, Na, Mg, and Al, whereas the major concentration of C, minor concentrations of N and O, and trace amounts of P and Ca were observed in the cholesterol-rich area. Hypercholesterolemia associated with calcification of this cardiac calculus was proposed. Both FE-SEM and ESEM energy dispersive X-ray microanalyses were performed directly, for the first time, to provide useful information on the microstructural characteristics and spatial distribution of elements on the surface of human cardiac calculi.

One-step simultaneous differential scanning calorimetry-FTIR microspectroscopy to quickly detect continuous pathways in the solid-state glucose/asparagine Maillard reaction.

The stepwise reaction pathway of the solid-state Maillard reaction between glucose (Glc) and asparagine (Asn) was investigated using simultaneous differential scanning calorimetry (DSC)-FTIR microspectroscopy. The color change and FTIR spectra of Glc-Asn physical mixtures (molar ratio = 1:1) preheated to different temperatures followed by cooling were also examined. The successive reaction products such as Schiff base intermediate, Amadori product, and decarboxylated Amadori product in the solid-state Glc-Asn Maillard reaction were first simultaneously evidenced by this unique DSC-FTIR microspectroscopy. The color changed from white to yellow-brown to dark brown, and appearance of new IR peaks confirmed the formation of Maillard reaction products. The present study clearly indicates that this unique DSC-FTIR technique not only accelerates but also detects precursors and products of the Maillard reaction in real time.

Thermal FT-IR microspectroscopy for rapid detection of solid-state ion-exchange reaction between metoclopramide HCl monohydrate and potassium bromide.

The combination of Fourier transform infrared (FT-IR) microspectroscopy with a thermal analyzer was applied to quickly investigate the solid-state ion-exchange reaction of metoclopramide HCl monohydrate (MCP H(2)O) by clipping MCP H(2)O powder between two KBr or KCl pellets. The physical and ground mixtures of MCP H(2)O or 150 °C-preheated MCP powder and KBr or KCl powders with a weight ratio of 1 : 100 were also prepared and determined by FT-IR microspectroscopy. The samples of MCP H(2)O or 150 °C-preheated MCP were identified by using differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis. The results of present study indicate that the ion-exchange reaction was easily induced between MCP H(2)O and KBr by grinding and heating processes. The possible mechanism of ion-exchange reaction may take place between the HCl salt of MCP H(2)O and a KBr matrix by grinding or heating to yield a mixture of HCl and HBr salts of the MCP sample in the presence of hydrated water. The crystal hydrate played an important role to improve this ion-exchange reaction between MCP H(2)O and KBr. However, no ion-exchange reaction occurred between MCP H(2)O and KCl or between 150 °C-preheated MCP and KBr. The solid-state ion-exchange reaction was more easily determined by this novel thermal FT-IR microspectroscopy than other conventional methods.

Simultaneous DSC-FTIR microspectroscopy used to screen and detect the co-crystal formation in real time.

We first report that the formation of pharmaceutical co-crystal can be synchronously screened and confirmed by a simultaneous DSC-FTIR microspectroscopic system, in which this combined unique system giving spectroscopic and thermodynamic information could provide a easy and direct way for one step screening and qualitative detection of the co-crystal formation in real time.

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.

Idiopathic calcinosis cutis in a child: chemical composition of the calcified deposits.

Idiopathic calcinosis cutis (CC) is a rare disease in a child. The chemical composition of the calcified deposits in idiopathic CC was first qualitatively and quantitatively examined using vibrational microspectroscopy via spectral diagnosis. The combined application of the Fourier transform infrared (FT-IR) and Raman microscopic techniques was used to detect and identify the nature of the components of the calcified deposits in idiopathic CC and to compare the results with histopathological findings. Two major components of type B carbonated apatite and ß-carotene interspersing subcutaneous tissue were clearly evidenced to make up the calcified deposits in idiopathic CC in our pediatric patient. Moreover, the calcified deposits of idiopathic CC contained a relatively larger amount of type B carbonated apatite and a smaller amount of type A carbonated apatite than the calcified deposits analyzed in dystrophic CC. This is the first report on the chemical composition of calcified deposits in idiopathic CC established by spectral analysis. The combination of FT-IR and Raman microscopic techniques was very useful for simultaneous assessment of the intact components of the calcified deposits in idiopathic CC.

Current and potential applications of simultaneous DSC-FTIR microspectroscopy for pharmaceutical analysis.

Quality control (QC) is the most important key issue in the pharmaceutical industry to ensure the quality of drug products. Many analytical instruments and techniques in pharmaceutical analysis are applied to assess the quality and quantity of the drugs. In the current and future trends, a combination of digitization, automation and hyphenation with high throughput on-line performance will be the topics for the future of pharmaceutical QC. The hyphenated analytical techniques have recently received great attention as unique means to solve complex analytical problems in a short period of time. This review article is an update on the recent potential applications of hyphenated technique developed from the coupling of a rapid separation or induction technique (differential scanning calorimetry; DSC) and an on-line spectroscopic (Fourier transform infrared; FTIR) detection technology to carry out an one-step solid-state analysis in pharmaceutical formulation developments, including (1) intramolecular condensation of pharmaceutical polymers, (2) intramolecular cyclization of drugs and sweetener, (3) polymorphic transformation of drugs and excipients, (4) drug-polymer (excipient) interaction, (5) fast cocrystal screening and formation. This simultaneous DSC-FTIR microspectroscopy can also provide an easy and direct method for one-step screening and qualitative detection of drug stability in real time.

Correlations among mineral components, progressive calcification process and clinical symptoms of calcific tendonitis.

OBJECTIVE: To establish the correlations among the mineral components, progressive calcification process and clinical symptoms of calcific tendonitis. METHODS: The morphology of the calcified deposits on the shoulders of 28 patients with calcific tendonitis was determined by high-resolution ultrasonography. The calcified deposit from each patient was aspirated and determined by the Fourier transform infrared and Raman microspectroscopies. The curve-fitting program was applied to estimate the chemical component in the calcified deposits of calcific tendonitis. RESULTS: The morphology of calcified deposits for 28 patients was classified into four shapes: arc shape (7 patients), fragmented/punctuate shape (4 patients), nodular shape (13 patients) and cystic shape (4 patients). These classified shapes markedly correlated with the pain levels in patients. The infrared spectra of all the calcified deposits for 28 patients were easily classified into three types in the blind study and corresponded to the formative, resting and resorptive phases in the progressive calcification process of calcific tendonitis. With the progressive calcification, the IR wavenumber at 1018 cm(-1) assigned to poorly crystalline, non-stoichiometric apatite for the formative phase was shifted to 1028 cm(-1) for the resting phase and then to 1031 cm(-1) due to matured crystalline stoichiometric apatite for the resorptive phase. The curve-fitted results revealed that calcified deposits in calcific tendonitis were composed of different quantities of A-type and B-type carbonated apatites in the three phases. A significant difference was found in carbonated apatite content among the three phases (P < 0.001). CONCLUSIONS: The different quantities of A-type and B-type carbonated apatites determined by vibrational microspectroscopy in calcified deposits were well correlated with those of the four shapes of morphologic classification, with the three phases in the progressive calcification process and with the clinical symptoms of calcific tendonitis.

Quantitation of ceramides in nude mouse skin by normal-phase liquid chromatography and atmospheric pressure chemical ionization mass spectrometry.

A sensitive and accurate normal-phase liquid chromatography and atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS) method for determining the standard ceramide [NS] (Cer[NS]) was developed and validated so as to improve the traditional thin-layer chromatography (TLC) technique and LC-electrospray ionization (ESI)-MS method to profile and quantify ceramides in nude mouse skin. Normal-phase LC-APCI-MS was optimized to separate the nine classes of ceramides presented in the stratum corneum (SC) of nude mouse skin. A normal-phase silica column eluted with the gradient system from heptane:acetone/butanol (90:10, v/v) of 75:25 to 100% acetone/butanol (90:10, v/v) (with each solvent containing 0.1% [v/v] triethylamine and 0.1% [v/v] formic acid) at a flow rate of 0.8 ml/min was found to be optimal for analyzing standard Cer[NS]. The analysis of Cer[NS] was validated and employed as the standard for constructing a calibration curve to quantitate all classes of ceramides. This method was applied to profile the classes and contents of ceramides in the SC of nude mouse skin and proved to be workable. It was concluded that this improved method can be used to directly detect and quantify all classes of ceramides in the SC of nude mouse skin and that it is more convenient and labor-saving than the traditional TLC method.

Progressive steps of polymorphic transformation of gabapentin polymorphs studied by hot-stage FTIR microspectroscopy.

PURPOSE: The aim of this study was to determine the progressive processes of polymorphic transformation of different gabapentin (GBP) polymorphs by using hot-stage Fourier transform infrared (FTIR) microspectroscopy. METHODS: Four polymorphs of GBP were previously prepared and then identified by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, FTIR microspectroscopy and X-ray powder diffractometry. A novel hot-stage FTIR microspectroscopic technique was used to investigate the progressive steps of polymorphic transformation of each GBP polymorph sealed within two pieces of KBr plates. RESULTS: Four polymorphs (Forms I, II, III and IV) of GBP were well characterized. The GBP form I was proven to be a monohydrate, but other GBP forms II-IV were anhydrous. Different thermal-induced progressive processes and steps of polymorphic interconversion of GBP polymorphs were clearly found from the changes in the three-dimensional IR spectral contour and peak intensity by using hot-stage FTIR microspectroscopy. The results also indicate that GBP form I was dehydrated and transformed to form III, and then converted to form IV; whereas GBP forms II and III directly transformed to form IV during heating. The GBP form IV was the last polymorph before the intramolecular lactamization of GBP. CONCLUSION: A one-step novel hot-stage FTIR microspectroscopy was successfully applied to simultaneously and continuously investigate the progressive processes and steps of thermal-induced polymorphic interconversion of GBP polymorph in the solid state.

Thermoresponsive gating membranes embedded with liquid crystal(s) for pulsatile transdermal drug delivery: An overview and perspectives.

Due to the circadian rhythm regulation of almost every biological process in the human body, physiological and biochemical conditions vary considerably over the course of a 24-h period. Thus, optimal drug delivery and therapy should be effectively controlled to achieve the desired therapeutic plasma concentrations and therapeutic drug responses at the required time according to chronopharmacological concepts, rather than continuous maintenance of constant drug concentrations for an extended time period. For many drugs, it is not always necessary to constantly deliver a drug into the human body under disease conditions due to rhythmic variations. Pulsatile drug delivery systems (PDDSs) have been receiving more attention in pharmaceutical development by providing a predetermined lag period, followed by a fast or rate-controlled drug release after application. PDDSs are characterized by a programmed drug release, which may release a drug at repeatable pulses to match the biological and clinical needs of a given disease therapy. This review article focuses on thermoresponsive gating membranes embedded with liquid crystals (LCs) for transdermal drug delivery using PDDS technology. In addition, the principal rationale and the advanced approaches for the use of PDDSs, the marketed products of chronotherapeutic DDSs with pulsatile function designed by various PDDS technologies, pulsatile drug delivery designed with thermoresponsive polymers, challenges and opportunities of transdermal drug delivery, and novel approaches of LC systems for drug delivery are reviewed and discussed. A brief overview of all academic research articles concerning single LC- or binary LC-embedded thermoresponsive membranes with a switchable on-off permeation function through topical application by an external temperature control, which may modulate the dosing interval and administration time according to the therapeutic needs of the human body, is also compiled and presented. In the near future, since thermal-based approaches have become a well-accepted method to enhance transdermal delivery of different water-soluble drugs and macromolecules, a combination of the thermal-assisted approach with thermoresponsive LCs membranes will have the potential to improve PDDS applications but still poses a great challenge.

Identification of monoclinic calcium pyrophosphate dihydrate and hydroxyapatite in human sclera using Raman microspectroscopy.

Raman microspectroscopy was first used to determine the composition of a calcified plaque located at the pterygium-excision site of a 51-year-old female patient's left nasal sclera after surgery. It was unexpectedly found that the Raman spectrum of the calcified sample at 1149, 1108, 1049, 756, 517, 376 and 352/cm was similar to the Raman spectrum of monoclinic form of calcium pyrophosphate dihydrate (CPPD) crystal, but differed from the Raman spectrum of triclinic form of CPPD. An additional peak at 958/cm was also observed in the Raman spectrum of the calcified plaque, which was identical to the characteristic peak at 958/cm of hydroxyapatite (HA). This is the first study to report the spectral biodiagnosis of both monoclinic CPPD and HA co-deposited in the calcified plaque of a patient with sclera dystrophic calcification using Raman microspectroscopy.

Spectral diagnosis and analysis of a superior vesical artery calcification.

A case of urinary vessel calcification was detected incidentally in pelvic cavity of a 59-year-old man by computed tomography. The silver reticulin, actin, and hematoxylin and eosin stains were applied to diagnose the feature of vessel and confirmed that the vessel was the vesical artery. To our knowledge, this is the first report to find out the obliteration of superior vesical artery caused by calcified deposit. The calcified deposit in superior vesical artery was qualitatively identified to consist of hydroxyapatite, cholesterol and beta-carotene by Fourier transform infrared and Raman microspectroscopies, in which A-type carbonated apatite was a predominate component.