Linking inflammation and angiogenesis with fibrogenesis: Expression of FXIIIA, MMP-9, and VEGF in oral submucous fibrosis / Vinculación de la inflamación y la angiogénesis con la fibrogénesis: expresión de FXIIIA, MMP-9 y VEGF en la fibrosis submucosa oral

Objectives Interplay of Factor XIIIa (FXIIIa), a transglutaminase, responsible for cross-linking of matrix proteins, Matrix Metalloproteinase-9 (MMP-9), a gelatinase, and Vascular Endothelial Growth Factor (VEGF), an angiogenic inducer, were studied in relation to fibrogenesis and disease progression in oral submucous fibrosis (OSMF). Material and methods Immunohistochemical expression of markers was studied in 60 formalin-fixed paraffin-embedded tissue blocks of OSMF and 20 normal oral mucosal tissues. FXIIIa was studied quantitatively while MMP-9 and VEGF were assessed semi-quantitatively. Expression was compared with histopathological grades of OSMF. Results FXIIIa expression significantly increased in OSMF (p-value 0.000). However, expression decreased and cells became quiescent with increasing grades (p-value 0.000). MMP-9 (p-value epithelium 0.011, p-value connective tissue 0.000) and VEGF expression (p-value epithelium 0.000, connective tissue 0.000) increased in OSMF. A negative correlation between FXIIIa and MMP-9 (−0.653) in early grade (p-value of 0.021) and a positive correlation between FXIIIa and VEGF (0.595) (p-value of 0.032) was found in the moderate grade OSMF. Regression analysis showed a significant association (p<0.01) of FXIIIa in OSMF and with increasing grades of OSMF. Conclusion FXIIIa may play a crucial role in initiation of fibrosis in OSMF. MMP-9 may have a diverse role to play in OSMF as a regulator of fibrosis. VEGF may show an angio-fibrotic switch and contribute to fibrosis in OSMF. These cytokines may show altered function and can contribute to fibrosis and chronicity of disease due to changes in the microenvironment. Tissue stiffness in OSMF itself creates an environment that enhances the chronicity of the disease. (AU)

Objetivos Se estudió la interacción del factor XIIIa (FXIIIa), una transglutaminasa responsable de los entrecruzamientos de las proteínas de la matriz, la metaloproteinasa de matriz-9 (MMP-9), una gelatinasa y el factor de crecimiento endotelial vascular (VEGF), un inductor angiogénico, en relación con la fibrogénesis y la progresión de la enfermedad en la fibrosis submucosa oral (OSMF). Material y métodos Se estudió la expresión inmunohistoquímica de marcadores en 60 bloques de tejido de OSMF fijados con formalina e incluidos en parafina y 20 tejidos de mucosa oral normales. FXIIIa se estudió cuantitativamente mientras que MMP-9 y VEGF se evaluaron semicuantitativamente. La expresión se comparó con los grados histopatológicos de OSMF. Resultados La expresión de FXIIIa aumentó significativamente en OSMF (valor de p 0,000). Sin embargo, la expresión disminuyó y las células se volvieron inactivas a medida que aumentaban los grados (valor de p 0,000). MMP-9 (valor de p epitelio 0,011, tejido conectivo valor de p 0,000) y expresión de VEGF (valor de p epitelio 0,000, tejido conectivo 0,000) aumentaron en OSMF. Se encontró una correlación negativa entre FXIIIa y MMP-9 (-0,653) en grado temprano (valor de p de 0,021) y una correlación positiva entre FXIIIa y VEGF (0,595) (valor de p de 0,032) en OSMF de grado moderado. El análisis de regresión mostró una asociación significativa (p<0,01) de FXIIIa en OSMF y con grados crecientes de OSMF. Conclusión FXIIIa puede desempeñar un papel crucial en el inicio de la fibrosis en OSMF. MMP-9 puede desempeñar un papel diverso en OSMF como regulador de la fibrosis. VEGF puede mostrar un interruptor angiofibrótico y contribuir a la fibrosis en OSMF. Estas citocinas pueden mostrar una función alterada y pueden contribuir a la fibrosis y la cronicidad de la enfermedad debido a cambios en el microambiente. La rigidez del tejido en el propio OSMF crea un entorno que mejora la cronicidad de la enfermedad. (AU)

Linking inflammation and angiogenesis with fibrogenesis: Expression of FXIIIA, MMP-9, and VEGF in oral submucous fibrosis / Vinculación de la inflamación y la angiogénesis con la fibrogénesis: expresión de FXIIIA, MMP-9 y VEGF en la fibrosis submucosa oral

Objectives Interplay of Factor XIIIa (FXIIIa), a transglutaminase, responsible for cross-linking of matrix proteins, Matrix Metalloproteinase-9 (MMP-9), a gelatinase, and Vascular Endothelial Growth Factor (VEGF), an angiogenic inducer, were studied in relation to fibrogenesis and disease progression in oral submucous fibrosis (OSMF). Material and methods Immunohistochemical expression of markers was studied in 60 formalin-fixed paraffin-embedded tissue blocks of OSMF and 20 normal oral mucosal tissues. FXIIIa was studied quantitatively while MMP-9 and VEGF were assessed semi-quantitatively. Expression was compared with histopathological grades of OSMF. Results FXIIIa expression significantly increased in OSMF (p-value 0.000). However, expression decreased and cells became quiescent with increasing grades (p-value 0.000). MMP-9 (p-value epithelium 0.011, p-value connective tissue 0.000) and VEGF expression (p-value epithelium 0.000, connective tissue 0.000) increased in OSMF. A negative correlation between FXIIIa and MMP-9 (−0.653) in early grade (p-value of 0.021) and a positive correlation between FXIIIa and VEGF (0.595) (p-value of 0.032) was found in the moderate grade OSMF. Regression analysis showed a significant association (p<0.01) of FXIIIa in OSMF and with increasing grades of OSMF. Conclusion FXIIIa may play a crucial role in initiation of fibrosis in OSMF. MMP-9 may have a diverse role to play in OSMF as a regulator of fibrosis. VEGF may show an angio-fibrotic switch and contribute to fibrosis in OSMF. These cytokines may show altered function and can contribute to fibrosis and chronicity of disease due to changes in the microenvironment. Tissue stiffness in OSMF itself creates an environment that enhances the chronicity of the disease. (AU)

Objetivos Se estudió la interacción del factor XIIIa (FXIIIa), una transglutaminasa responsable de los entrecruzamientos de las proteínas de la matriz, la metaloproteinasa de matriz-9 (MMP-9), una gelatinasa y el factor de crecimiento endotelial vascular (VEGF), un inductor angiogénico, en relación con la fibrogénesis y la progresión de la enfermedad en la fibrosis submucosa oral (OSMF). Material y métodos Se estudió la expresión inmunohistoquímica de marcadores en 60 bloques de tejido de OSMF fijados con formalina e incluidos en parafina y 20 tejidos de mucosa oral normales. FXIIIa se estudió cuantitativamente mientras que MMP-9 y VEGF se evaluaron semicuantitativamente. La expresión se comparó con los grados histopatológicos de OSMF. Resultados La expresión de FXIIIa aumentó significativamente en OSMF (valor de p 0,000). Sin embargo, la expresión disminuyó y las células se volvieron inactivas a medida que aumentaban los grados (valor de p 0,000). MMP-9 (valor de p epitelio 0,011, tejido conectivo valor de p 0,000) y expresión de VEGF (valor de p epitelio 0,000, tejido conectivo 0,000) aumentaron en OSMF. Se encontró una correlación negativa entre FXIIIa y MMP-9 (-0,653) en grado temprano (valor de p de 0,021) y una correlación positiva entre FXIIIa y VEGF (0,595) (valor de p de 0,032) en OSMF de grado moderado. El análisis de regresión mostró una asociación significativa (p<0,01) de FXIIIa en OSMF y con grados crecientes de OSMF. Conclusión FXIIIa puede desempeñar un papel crucial en el inicio de la fibrosis en OSMF. MMP-9 puede desempeñar un papel diverso en OSMF como regulador de la fibrosis. VEGF puede mostrar un interruptor angiofibrótico y contribuir a la fibrosis en OSMF. Estas citocinas pueden mostrar una función alterada y pueden contribuir a la fibrosis y la cronicidad de la enfermedad debido a cambios en el microambiente. La rigidez del tejido en el propio OSMF crea un entorno que mejora la cronicidad de la enfermedad. (AU)

Linking inflammation and angiogenesis with fibrogenesis: Expression of FXIIIA, MMP-9, and VEGF in oral submucous fibrosis.

OBJECTIVES: Interplay of Factor XIIIa (FXIIIa), a transglutaminase, responsible for cross-linking of matrix proteins, Matrix Metalloproteinase-9 (MMP-9), a gelatinase, and Vascular Endothelial Growth Factor (VEGF), an angiogenic inducer, were studied in relation to fibrogenesis and disease progression in oral submucous fibrosis (OSMF). MATERIAL AND METHODS: Immunohistochemical expression of markers was studied in 60 formalin-fixed paraffin-embedded tissue blocks of OSMF and 20 normal oral mucosal tissues. FXIIIa was studied quantitatively while MMP-9 and VEGF were assessed semi-quantitatively. Expression was compared with histopathological grades of OSMF. RESULTS: FXIIIa expression significantly increased in OSMF (p-value 0.000). However, expression decreased and cells became quiescent with increasing grades (p-value 0.000). MMP-9 (p-value epithelium 0.011, p-value connective tissue 0.000) and VEGF expression (p-value epithelium 0.000, connective tissue 0.000) increased in OSMF. A negative correlation between FXIIIa and MMP-9 (-0.653) in early grade (p-value of 0.021) and a positive correlation between FXIIIa and VEGF (0.595) (p-value of 0.032) was found in the moderate grade OSMF. Regression analysis showed a significant association (p<0.01) of FXIIIa in OSMF and with increasing grades of OSMF. CONCLUSION: FXIIIa may play a crucial role in initiation of fibrosis in OSMF. MMP-9 may have a diverse role to play in OSMF as a regulator of fibrosis. VEGF may show an angio-fibrotic switch and contribute to fibrosis in OSMF. These cytokines may show altered function and can contribute to fibrosis and chronicity of disease due to changes in the microenvironment. Tissue stiffness in OSMF itself creates an environment that enhances the chronicity of the disease.

Biofabrication of nanoparticles: sources, synthesis, and biomedical applications.

Nanotechnology is an emerging applied science delivering crucial human interventions. Biogenic nanoparticles produced from natural sources have received attraction in recent times due to their positive attributes in both health and the environment. It is possible to produce nanoparticles using various microorganisms, plants, and marine sources. The bioreduction mechanism is generally employed for intra/extracellular synthesis of biogenic nanoparticles. Various biogenic sources have tremendous bioreduction potential, and capping agents impart stability. The obtained nanoparticles are typically characterized by conventional physical and chemical analysis techniques. Various process parameters, such as sources, ions, and temperature incubation periods, affect the production process. Unit operations such as filtration, purification, and drying play a role in the scale-up setup. Biogenic nanoparticles have extensive biomedical and healthcare applications. In this review, we summarized various sources, synthetic processes, and biomedical applications of metal nanoparticles produced by biogenic synthesis. We highlighted some of the patented inventions and their applications. The applications range from drug delivery to biosensing in various therapeutics and diagnostics. Although biogenic nanoparticles appear to be superior to their counterparts, the molecular mechanism degradation pathways, kinetics, and biodistribution are often missing in the published literature, and scientists should focus more on these aspects to move them from the bench side to clinics.

Surface Functionalization of Nanofibers: The Multifaceted Approach for Advanced Biomedical Applications.

Nanocarriers are gaining significant importance in the modern era of drug delivery. Nanofiber technology is one of the prime paradigms in nanotechnology for various biomedical and theranostic applications. Nanofibers obtained after successful electrospinning subjected to surface functionalized for drug delivery, biomedical, tissue engineering, biosensing, cell imaging and wound dressing application. Surface functionalization entirely changes physicochemical and biological properties of nanofibers. In physicochemical properties, wettability, melting point, glass transition temperature, and initial decomposition temperature significantly change offer several advantageous for nanofibers. Similarly, biological properties include cell adhesion, biocompatibility, and proliferation, also changes by functionalization of nanofibers. Various natural and synthetic materials polymers, metals, carbon materials, functional groups, proteins, and peptides, are currently used for surface modification of nanofibers. Various research studies across the globe demonstrated the usefulness of surface functionalized nanofibers in tissue engineering, wound healing, skin cancers, melanoma, and disease diagnosis. The delivery of drug through surface functionalized nanofibers results in improved permeation and bioavailability of drug which is important for better targeting of disease and therapeutic efficacy. This review provides a comprehensive insight about various techniques of surface functionalization of nanofibers along with its biomedical applications, toxicity assessment and global patent scenario.

Recent Advancements in Microneedle Technology for Multifaceted Biomedical Applications.

Microneedle (MNs) technology is a recent advancement in biomedical science across the globe. The current limitations of drug delivery, like poor absorption, low bioavailability, inadequate skin permeation, and poor biodistribution, can be overcome by MN-based drug delivery. Nanotechnology made significant changes in fabrication techniques for microneedles (MNs) and design shifted from conventional to novel, using various types of natural and synthetic materials and their combinations. Nowadays, MNs technology has gained popularity worldwide in biomedical research and drug delivery technology due to its multifaceted and broad-spectrum applications. This review broadly discusses MN's types, fabrication methods, composition, characterization, applications, recent advancements, and global intellectual scenarios.

Comprehensive Review on the Degradation Chemistry and Toxicity Studies of Functional Materials.

In recent decades there has been growing interest of material chemists in the successful development of functional materials for drug delivery, tissue engineering, imaging, diagnosis, theranostic, and other biomedical applications with advanced nanotechnology tools. The efficacy and safety of functional materials are determined by their pharmacological, toxicological, and immunogenic effects. It is essential to consider all degradation pathways of functional materials and to assess plausible intermediates and final products for quality control. This review provides a brief insight into chemical degradation mechanisms of functional materials like oxidation, photodegradation, and physical and enzymatic degradation. The intermediates and products of degradation were confirmed with analytical methods such as proton nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), UV-vis spectroscopy (UV-vis), infrared spectroscopy (IR), differential scanning calorimetry (DSC), mass spectroscopy, and other sophisticated analytical methods. These analytical methods are also used for regulatory, quality control, and stability purposes in industry. The assessment of degradation is important to predetermine the behavior of functional materials in specific storage conditions and can be relevant to their behavior during in vivo applications. Another important aspect is the evaluation of the toxicity of functional materials. Toxicity can be accessed with various methods using in vitro, in vivo, ex vivo, and in silico models. In vitro cell culture methods are used to determine mitochondrial damage, reactive oxygen species, stress responses, and cellular toxicity. In vitro cellular toxicity can be measured by MTT assay, LDH leakage assay, and hemolysis. In vivo studies are performed using various animal models involving zebrafish, rodents (mice and rats), and nonhuman primates. Ex vivo studies are also used for efficacy and toxicity determinations of functional materials like ex vivo potency assay and precision-cut liver slice (PCLS) models. The in silico tools with computational simulations like quantitative structure-activity relationships (QSAR), pharmacokinetics (PK) and pharmacodynamics (PD), dose and time response, and quantitative cationic-activity relationships ((Q)CARs) are used for prediction of the toxicity of functional materials. In this review, we studied the principle methods used for degradation studies, different degradation pathways, and mechanisms of functional material degradation with prototype examples. We discuss toxicity assessments with different toxicity approaches used for estimation of the safety and efficacy of functional materials.

Development and pharmacokinetic evaluation of osmotically controlled drug delivery system of Valganciclovir HCl for potential application in the treatment of CMV retinitis.

Valganciclovir HCl (VGH) is the widely used drug for the treatment of cytomegalovirus (CMV) retinitis infection with an induction dose of 900 mg per oral (p.o.) twice a day and a maintenance dose of 900 mg (p.o.). This required dose of the drug also leads to multiple side effects due to repeated administration. The research was highlighted to develop, formulate, optimize, and evaluate single-core osmotic pump (SCOP) tablet of VGH with the dose of 450 mg to reduce dosing frequency and associated side effects. The decrease in dose also minimizes the hepatic and nephrotic load. The optimized batch of the formulation was subjected to comparative in vitro and in vivo evaluation. The tablet core composition is the primary influencer of the drug delivery fraction in a zero order, whereas the membrane characteristics control the drug release rate. In vivo pharmacokinetic studies revealed that the newly developed osmotic formulation has controlled zero-order release for 24 h with a single dose of 450 mg while the marketed formulation requires twice administration within 24 h to maintain the plasma concentration in the therapeutic window. The pharmacokinetic study demonstrated that the developed formulation has the area under curve (AUC) of 58.415 µg h/ml with single dose while the marketed formulation shows the AUC of about 37.903 µg h/ml and 31.983 µg h/ml for first and second dose, respectively. The large AUC demonstrates the extended release of drug with a single dose and effective plasma concentration. Hence, the developed formulation can be a promising option for the treatment of CMV retinitis with the minimum dose and dosing frequency.

Mometasone furoate-loaded aspasomal gel for topical treatment of psoriasis: formulation, optimization, in vitro and in vivo performance.

BACKGROUND: Present investigation was aimed to develop aspasomal gel of Mometasone Furoate for the treatment of Psoriasis that are biologically active and deliver drug at controlled rate and decrease dosing frequency. METHODS: The vesicles were fabricated using film hydration method and optimized using 32 factorial Design. Prepared formulations were evaluated for percent drug loading, vesicle size, Zeta potential, polydispersity index and morphological studies. Gel was prepared using carbopol by loading optimized drug loaded asposomes and was evaluated for drug content, pH, viscosity and spreadability. The drug release study from the gel was done using dialysis membrane and goat skin. Anti- oxidant potency of the prepared aspasomal gel was determined by Ferric Reducing Assay whereas, in-vivo performance for inflammation and skin irritation was carried out using Wistar rats. RESULTS: Optimized aspasomes demonstrated desired properties for entrapment efficiency (74.72 ± 1.8), vesicle size (282.9 ± 1.7), polydispersity index (0.2), zeta potential (-20.2 mV) with spherical shape. The results recorded for drug release from the optimized aspasomal gel exhibited sustained release (24h) compared to the marketed cream (5h). Depot formation of Mometasone furoate loaded aspasomal gel in the epidermis was confirmed by ex vivo skin penetration study by using fluorescent marker. In-vivo study revealed no any irritation and inflammation to the skin promoting drug delivery system to treat psoriasis. CONCLUSION: In conclusion, Mometasone furoate loaded aspasomal gel releases the drug for longer duration of time and reduce dosing frequency, providing the new dimension for the treatment of psoriasis.

Development, evaluation and biodistribution of stealth liposomes of 5-fluorouracil for effective treatment of breast cancer.

The current research was undertaken to design stealth liposomes of 5-Fluorouracil for reducing its cardiotoxicity and prolong the half-life by developing long-circulating liposomes. The liposomes were prepared by the NH4EDTA gradient method, where EDTA is used as a cardioprotectant. Ascorbyl-6-palmitate was also used which helped for the synergistic effect of 5-Fluorouracil to counteract the cancer cells and provide promising application in the treatment of breast cancer cells. Taguchi design was used for screening of formulation and HSPC phospholipid was selected. The drug-excipient compatibility was checked through FTIR which showed all the excipients were compatible with the drug. The formulation was optimized by using 32 factorial design. The drug to lipid ratio (1:5) and Ascorbyl-6-Palmitate concentration (15 mg) were selected. The vesicle size of the prepared liposomes was found to be 70.12 ± 0.58 nm and uniform distribution was observed. The zeta potential and entrapment efficiency of the stealth liposomes were found -16.28 mV and 92 ± 0.007% respectively. In-vitro drug release study of formulation showed drug release of 63.50 ± 0.94% in 24 hrs. The formulation was sterilized by 0.22 µm Mixed cellulose esters (MCE) membrane filter and passed sterility test. Moreover, a biodistribution study was performed by Fluorescence microscopy and by HPLC method, which showed formulation was circulated for 24 hours. Finally, a cell line study indicated that prepared formulation possess greater anti-tumour activity. The cardiotoxicity study revealed that the stealth liposomes have minimum cardiotoxicity as compare to the plain drug.

Solid State Characterization and Dissolution Enhancement of Nevirapine Cocrystals.

Purpose: Novel cocrystals of nevirapine (NP) were designed and prepared with salicylamide and 3-hydroxy benzoic acid (3-HBA). Methods: The cocrystals were prepared by solvent drop grinding method by adding few drops of acetone to enhance the solubility and dissolution. The drug and cocrystals were characterized by differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD). The solubility of NP, its wet ground form, and cocrystals were investigated at different pH. Moreover, the effect of surfactant on solubility of cocrystals was also studied. Finally, intrinsic dissolution rate (IDR) and stability of cocrystals was examined. Results: The characterization of cocrystals by DSC and PXRD revealed formation of new solid forms due to changes in thermogram and PXRD pattern. The cocrystal of NP with 3-HBA showed 4.5 folds greater solubility in pH 1.2 buffer and 5.5 folds in 1% Tween 80 as compared to original drug. IDR of cocrystals was higher than the pure drug in 0.1 N hydrochloric acid (HCl). Moreover, cocrystals were found physically stable after 3 months as evident from unchanged IDR. Conclusion: Hence, the present research indicates the new stable solid forms of NP with improved dissolution rate than pure drug.

Evaluation and Comparison of Human Chorionic Amniotic Membrane and Platelet-Rich Fibrin in Achieving Bone Formation and Soft Tissue Healing in Extraction Sockets Indicated for Rehabilitation with Implants: A Preliminary Study.

PURPOSE: To evaluate and compare human chorionic amniotic membrane and platelet-rich fibrin on new bone formation and soft tissue healing in extraction sockets indicated for rehabilitation with dental implants. MATERIALS AND METHODS: A prospective, triple blind clinical study was conducted. The inclusion criteria were as follows: patient with two extraction sites each in the same arch, intact buccal bone and soft tissue around the socket, and recommended rehabilitation with dental implants. Postextraction, the sockets were randomly placed with human chorionic amniotic membrane in one site and platelet-rich fibrin in the other site. After 3 months, a trephine drill was used to take a biopsy of the respective sites for soft and hard tissue samples. The outcome parameters that were assessed histologically were percentage of new bone formation and lymphocyte density. RESULTS: After screening 80 patients, eight participants were recruited for the study. The mean percentage of new bone formation in the human chorionic amniotic membrane group was 45.71% ± 4.82%, and for the plasma-rich fibrin group, it was 41.39% ± 6.29%, showing no statistically significant difference (z = 0.99, P = .31). In the human chorionic amniotic membrane group, six out of eight sites had mild lymphocyte density, while the plasmarich fibrin group had equal numbers of mild and moderate lymphocyte density. No statistically significant difference between the groups (Fischer test value = 0.60, P = .25) was noted. CONCLUSION: Within the limitations of the study, the results showed that there is no difference in the efficiency of human chorionic amniotic membrane compared with platelet-rich fibrin in achieving new bone formation and soft tissue healing in the extraction socket.

Enhanced brain targeting efficiency using 5-FU (fluorouracil) lipid-drug conjugated nanoparticles in brain cancer therapy.

The present investigation was aimed to synthesize, optimize, and characterize lipid/drug conjugate nanoparticles for delivering 5-fluorouracil (5-FU) to treat brain cancer. The Box-Behnken design was used to optimize the formulation, evaluate the particle size, entrapment efficiency, morphology, in vitro drug release study, and stability profiles. The in vitro performance was executed using cell line studies. The in vivo performance was carried out for pharmacokinetic studies, sterility test, biodistribution studies, and distribution lipid-drug conjugated (LDC) nanoparticles in the brain. Particle size, zeta potential, entrapment efficiency, and morphology of the optimized formulation demonstrated desirable results. In vitro release pattern showed initial fast release, followed by sustained release up to 48 h. Cytotoxic effects of blank stearic acid nanoparticles, LDC nanoparticles, and 5-FU solution on human glioma cell lines U373 MG cell showed more cytotoxicity by LDC-NPs compared to others. The values reported for LDC (AUC = 19.37 ± 0.09 µg/mL h and VD 2.4 ± 0.24 mL) and pure drug (AUC = 8.37 ± 0.04 µg/mL h and VD = 5.24 ± 0.29 mL) indicate higher concentrations of LDC in systemic circulation, while pure 5-FU was found to be largely available in tissue rather than blood circulation. The t1/2 for LDC represents an approximate rise by ninefold, while MRT (12.10 ± 0.44 h) denotes 12-fold rise than pure 5-FU indicating the prolonged circulation of LDC. Free 5-FU concentration in the brain was maximum (5.24 ± 0.01 µg/g) after 3 h, while for the optimized formulation of LDC it was twofold greater estimated as 11.52 ± 0.32 µg/g. In conclusion, the efficiency of 5-FU to treat the brain is increased when it is formulated with LDC nanoparticles.

Laser pilonidotomy - a new approach in management of complex pilonidal sinus disease: an exploratory study / Pilonidotomia a laser - uma nova abordagem no tratamento da doença do seio pilonidal complexo: um estudo exploratório

Abstract Background The treatment of pilonidal sinus disease still remains challenging mainly because of multiple factors responsible for wound healing and its recurrence. With recent advances in surgical field, use of laser found to be an effective technique in the destruction of a pilonidal cyst. Laser Piolonidotomy is a new promising technique. Methodology An exploratory study was planned with the Aim, to evaluate a new technique for the excision of pilonidal sinus. Objectives were to investigate its effectiveness in terms of operation time, healing time, and the duration of hospitalization, resumption of normal activity the degree of postoperative complications and rate of recurrence and patient's satisfaction. All the patients with pilonidal sinus were categorized and laser pilonidotomy was planned for patients satisfying inclusion criteria. Data collected in pre-structured, pre-tested proforma and analyzed using SPSS. Results Mean duration of Procedure was 33 min (SD = 11), mean duration of Hospital Stay was 12 h (SD = 3), resumption of normal activity within 4 days (SD = 2), mean duration for Complete Wound Healing by secondary intention 6 Weeks (SD = 1.25). Among complications, infection reported in 1.08%. The difference between the mean pre and post-operative VAS score was statistically highly significant (p < 0.0001). Recurrence rate was 3.24%. Success rate was 96.75% and Overall patient's satisfaction was 97.84%. Conclusion Laser Pilonidotomy is effective in destruction of a pilonidal cyst with good success rate, fewer complications and with high patient's satisfaction.

Resumo Justificativa O tratamento da doença do seio pilonidal ainda permanece desafiador, principalmente devido a vários fatores responsáveis pela cicatrização das feridas e sua recorrência. Com os recentes avanços no campo cirúrgico, o uso do laser mostrou ser uma técnica eficaz na destruição de um cisto pilonidal. A piolonidotomia a laser é uma nova técnica promissora. Metodologia Foi planejado um estudo exploratório com o objetivo de avaliar uma nova técnica para a excisão de seio pilonidal. Os objetivos foram investigar sua eficácia quanto aos tempos de operação, de cicatrização, de internação e de retomada da atividade normal, além do grau de complicações pós-operatórias, a taxa de recorrência e o índice de satisfação do paciente. Todos os pacientes com seio pilonidal foram categorizados, e a pilonidotomia a laser foi planejada para os pacientes que satisfizessem os critérios de inclusão. Os dados foram coletados em forma pré-estruturada e pré-testada e analisados usando o SPSS. Resultados O tempo médio do procedimento foi de 33 min (DP = 11), o tempo médio da internação hospitalar foi de 12 horas (DP = 3), o tempo médio de retomada da atividade normal foi de 4 dias (DP = 2) e o tempo médio de cicatrização completa por intenção secundário foi de 6 semanas (DP = 1,25). Entre as complicações, infecção foi observada em 1,08%. A diferença entre as médias do escore EVA pré e pós-operatório foi estatisticamente significativa (p < 0,0001). A taxa de recorrência foi de 3,24%. A taxa de sucesso foi de 96,75% e o índice de satisfação geral do paciente foi de 97,84%. Conclusão A pilonidotomia a laser é eficaz na destruição de um cisto pilonidal com boa taxa de sucesso, menos complicações e com alta satisfação do paciente.

Sustained release formulation of Ondansetron HCl using osmotic drug delivery approach.

Ondansetron HCl (OSH) is a 5-HT3 receptor antagonist indicated for the prevention of nausea and vomiting associated with radiotherapy (adults: 8 mg, t.i.d) and/or chemotherapy (adults: 8 mg, b.i.d to t.i.d) and prevention of postoperative nausea and/or vomiting (adults: 8 mg, b.i.d). In elderly subjects, bioavailability may be somewhat higher (65%) and lower clearance, presumably due to reduced hepatic first-pass metabolism. OSH is extensively distributed in the body; about 70-75% of the drug in plasma is protein-bound and terminal elimination half-life is about 3 h after oral administration. The study was aimed to develop Push-pull Osmotic Pump (PPOP) bi-layered tablets for Ondansetron HCl ER tablets. The granulation was carried out using non-aqeous solvents followed by compression, seal coating, semi permeable coating, laser drilling (0.6 mm), and drug film coating with loading dose. The drug release was controlled by swelleable osmotic polymers of pull layer and push layer and orifice on the surface of tablet. The formulations were optimized for its core composition, extended release coating (Semipermeable membrane) polymer as to plasticizer ratio and orifice diameter. Optimized formulations were evaluated for micromeritic properties and in vitro drug release. The analytical methods were developed and validated to estimate in vitro drug potency, drug release, and in vivo pharmacokinetic parameters. Stability studies were done as per the ICH guidelines. The results of in vivo study concludes that the once OSH ER dose consistently maintains plasma concentration of drug within the therapeutic window over a period of 24 h.

Comparative evaluation of 2-point vs 3-point fixation in the treatment of zygomaticomaxillary complex fractures - A systematic review.

BACKGROUND: The zygomaticomaxillary complex (ZMC) functions as the main buttress for the lateral portion of the middle third of the facial skeleton and because of its prominent position & convex shape, it is frequently fractured, alone or along with other bones of the midface. The management of the ZMC fractures is debatable as the literature is saturated with various theories. A number of techniques, from closed reduction to open reduction and internal fixation can be effectively used to manage these fractures. Controversies lie right from the amount of fixation (1-, 2-, 3- or 4- point fixation) required to the ideal approach, and there is no conclusive view on its ideal line of management. OBJECTIVE: To compare Malar asymmetry after 2-point vs 3-point fixation in the treatment of zygomaticomaxillary complex fractures. DATA SOURCE: Electronic search of Pub Med, Google Scholar, Institutional Library, Email to authors and manual search of various journals. STUDY ELIGIBILITY CRITERIA: The following criteria were used to select the studies on 2- point and 3-point fixation methods in Zygomaticomaxillary complex fractures. Inclusion criteria had articles that included clinical studies published in the English language or those having sufficient data in English on 2-point or 3-point fixation in the treatment of zygomaticomaxillary complex fractures between the period of 1st January 2008 to 30th September 2018. While exclusion criteria were articles not published in the English language before 1st January 2008 and after 30th September 2018, any reviews, abstracts, letters to editors, editorials and in vitro studies were excluded. Studies that included patients with craniofacial and secondary deformities were also excluded. INTERVENTION: Open reduction and internal fixation using 2-point and 3-point fixation methods in the treatment of Zygomaticomaxillary complex fractures. RESULTS: Preliminary screening consisted of 757 studies and additional records identified through other sources of 272 studies. Amongst these 1029 studies, 837 studies were excluded after reviewing the titles. A review of abstract further excluded 71 studies, so 34 studies that remained were evaluated to fit the eligibility criteria. On the basis of information on fixation methods and parameters of evaluation of fixation method, 26 studies were further excluded. Thus 8 studies with a total of 823 estimates were included in qualitative synthesis. LIMITATIONS: Parameters assessed by all the authors varied and hence a standardisation for comparison could not be done. CONCLUSION: Five out of eight studies showed that the use of 3-point fixation in the treatment of zygomaticomaxillary complex fractures was superior than 2-point fixation for the same. Hence it can be concluded that 3-point fixation is superior than 2-point fixation in reducing malar asymmetry in zygomaticomaxillary complex fractures. FUTURE IMPLICATIONS: Future studies with uniform parameters being assessed can be done. 3-point fixation can be used as a standard treatment modality in the effective management of Zygomaticomaxillary complex fractures.

A Prospective Open-labeled Study of Tattoo Removal with Q-Switched Nd:YAG Laser Utilizing the R0 Technique and Correlation with Kirby-Desai Scale.

INTRODUCTION: The Q-switched Nd: YAG (QSNY) laser is considered the standard device of choice for laser tattoo removal. Newer concepts such as R0 , R20 methods aided in faster clearance of tattoos. The Kerby-Desai scale [KD scale] has been proposed to predict the approximate number of sessions needed for tattoo clearance. OBJECTIVE: To access the efficacy of R0 technique for tattoo removal in skin types IV to VITo evaluate the Kerby-Desai scale and its correlation to the number of sessions actually required for tattoo clearance. MATERIAL AND METHODS: Twenty-two patients with single colored amateur were treated using modified R0 technique and the number of sessions were corelated with Kirby Desai scale. RESULTS: We found that R0 method require significantly less sessions than predicted by KD scale. CONCLUSION: Tattoo removal with the R0 technique using PFD allows faster clearing of tattoos and significantly cuts down the total treatment duration needed for tattoo removal.

Comparison of TORS with Conventional Surgery for Oropharyngeal Carcinomas in T1-T4 Lesions.

OBJECTIVES: Transoral Robotic Simulation (TORS) is an innovative surgical technique indicated for resection of selected head-and-neck cancers. The authors conducted a systematic review discussing the indications, advantages, and disadvantages of this technique. DATA SOURCES: The search included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, COCHRANE, and bibliographies of relevant studies through January 2006. MATERIALS AND METHODS: Studies included patients treated for T1-T4 stage oropharynx cancer with TORS. Study retrieval and data extraction were conducted in duplicate and resolved by consensus. Treatment specific details, as well as recurrence, survival, and adverse events, were collected. Methodological quality for each study was appraised. RESULTS: Nine studies were included which met the inclusion criteria. Patients receiving TORS required adjuvant radiotherapy (26%) or chemoradiotherapy (41%). Two-year overall survival estimates ranged from 82% to 94% for TORS. CONCLUSION: The minimally invasive transoral robotic simulation (TORS) for the treatment of oropharyngeal cancers is proved to be less time-consuming, compliant to the patients, and having less complications as compared to the more invasive techniques involving conventional surgery although the quality of this evidence is limited.

Long term explant culture for harvesting homogeneous population of human dental pulp stem cells.

Dental pulp stem cells have emerged as a preferred source of mesenchymal stem cells, because of its easy availability and high stem cell content. Dental pulp is a specific fibrous tissue that contains heterogeneous populations of odontoblasts, fibroblasts, pericytes, progenitors, stem cells, leukocytes and neuronal cells. In this study, we propose sustained explant culture as a simple, economical and efficient process to isolate dental pulp stem cells from human Dental pulp Tissue. Historically explant cultures were used to get fibroblast cells from embryonic chick heart using plasma clot cultures. The subculture was performed by lifting mother explant (original explant) and grafting it in a new plasma clot. We modified this age old technique to suit the modern times. Here we demonstrate for the first time that the mother explant (E0) of human dental pulp tissue could be sub-cultured consecutively seven times (E7) without displacement. This technique is highly reproducible and permits growth and proliferation of dental pulp stem cells yielding an enriched homogeneous mesenchymal stem cells population in the first passage itself as revealed by surface marker expression. These dental pulp stem cells exhibit differentiation into adipogenic, chondrogenic and osteogenic lineage revealing their mesenchymal stem cell nature. We propose that dental pulp stem cells isolated by sustained explant culture are phenotypically and functionally comparable to those obtained by enzymatic method. It is a simple, inexpensive and gentle method, which may be preferred over the conventional techniques for obtaining stem cells from other tissue sources as well especially in cases of limited starting material.

Odontome, Cyst, Impacted Tooth, and Space Infection in a Single Patient: All-in-One Diagnostic Dilemma.

This case report analyzes the clinical and radiographic features of odontogenic infection with underlying pathology. Systematic approach leads to narrow the differential diagnosis on the basis of exclusion. This results in correct diagnosis, proper treatment, and avoiding unnecessary treatment. This case report highlighted an unusual case of odontogenic infection involving adjacent fascial spaces with underlying pathology which was mimicking a cyst, tumor, and odontome. Systematic approach helped us achieve accurate diagnosis, treatment, and avoiding complications.