Role of Doxycycline as an Osteoarthritis Disease-Modifying Drug.

Doxycycline is a drug that has been proposed to modify osteoarthritis (OA) progression, in addition to its role as an antibiotic. However, available evidence thus far comprises sporadic reports, with no consensus on its benefits. Hence, this review attempts to analyze the evidence available thus far on the role of doxycycline as a disease-modifying osteoarthritis drug (DMOAD) in knee osteoarthritis. The earliest evidence of doxycycline in OA appeared in 1991 when doxycycline was found to inhibit the type XI collagenolytic activity of extracts from the human osteoarthritic cartilage, and gelatinase and tetracycline were found to inhibit this metalloproteinase activity in articular cartilage in vivo, which could modify cartilage breakdown in osteoarthritis. Apart from the inhibition of cartilage damage by metalloproteinases (MMPs) and other cartilage-related mechanisms, doxycycline also affects the bone and interferes with many enzyme systems. The most significant finding after reviewing various studies was that doxycycline has a definitive role in structural changes in osteoarthritis progression and radiological joint space width, but its role in the improvement of clinical outcomes as a DMOAD has not been established. However, there is much of a gap and lack of evidence in this regard. Doxycycline, as an MMP inhibitor, has theoretical advantages for clinical outcomes, but the present studies reveal only beneficial structural changes in osteoarthritis and very minimal or nonexistent advantages in clinical outcomes. Current evidence does not favor the regular use of doxycycline for the treatment of osteoarthritis as an individual treatment option or in combination with others. However, multicenter large cohort studies are warranted to determine the long-term benefits of doxycycline.

Level of Resilience Among Transgenders in Selected Areas of Puducherry, India: An Exploratory Research.

Background Resilience is the process of adapting well in the face of adversity, trauma, tragedy, threats, or significant sources of stress, and it is a predictor of mental health status that specifically indicates self-esteem, perceived social support, emotion-oriented coping, and a sense of personal mastery. The third gender known better as transgender has existed in every culture, race, class, and religion since the inception of human life has been recorded and analyzed. In spite of many advances and reforms, the current plight of transgender is far from being satisfactory. The social integration of transgender with the mainstream community is practically non-existent even today. Aim and objective The objective of the study is to assess the level of resilience among transgenders at selected areas in Puducherry, India, and to find out the association between the levels of resilience among transgenders with the selected demographic variables. Methods A descriptive cross-sectional study was conducted in the selected areas of Puducherry, India, adopting a linear snowball sampling method after consultation with the Nayaks (heads of transgenders) of the transgender groups, and 100 transgenders were enrolled who fulfilled the inclusion criteria and consented to participate in the research. Results About 29 (29%) transgenders were in the age group of 31-40 years, 28 (28%) were in the age group of 21-30 years, 24 (24%) were in the group of 41-50 years, and 19 (19%) were in the age group of 51 and above. In education status, 38 (38%) had secondary education, 23 (23%) had primary education, 20 (20%) had higher secondary education, 12 (12%) had graduation and above, and seven (7%) were diploma holders. Moreover, 54 (54%) were employed, and 46 (46%) were unemployed; 81 (81%) were residing in rural areas, and 19 (19%) were residing in urban areas. The study revealed that 53 (53%) of them had average resilience, 28 (28%) had the least resilience, and 19 (19%) had the highest resilience among transgenders. The minimum score was 28.0, and the maximum score was 52.0. The mean score was 42.50 with a standard deviation of 4.61. The median value was 43.0. Conclusion Transgenders exhibit low and average resilience that reflects poor mental health status among them. The educational status was found to be associated with the level of resilience. Proper education among transgenders would help in improving their resilience and betterment of their life.

Assessment of safety and efficacy of intra-articular injection of stromal vascular fraction for the treatment of knee osteoarthritis-a systematic review.

PURPOSE: Stromal vascular fraction (SVF) as an injectable regenerative therapy for knee osteoarthritis (OA) has gained recent popularity. However, there is no clear consensus on the outcomes of such treatment. We systematically reviewed available evidence on the use of SVF injection in the treatment of knee OA. METHODS: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with keyword search in PubMed, Scopus, and the Cochrane Library Database and related article search in Google Scholar. Clinical studies demonstrating effects of SVF in knee OA and published in English literature were included. Risk of bias assessment was done with modified Coleman Methodology Scoring (CMS). RESULTS: Eleven studies (9 prospective, 2 retrospective) that contributed to 290 knees in 200 patients were included. Two studies that contributed to 3718 knee injections were excluded from pooled analysis and were scrutinized separately. Majority of patients reported improvement in pain, range of motion (ROM), functional rating, six metre walking distance, and functional outcome scores. There was no major donor-site morbidity. There was only one reported case of knee joint infection and no case of tumour formation in relation to SVF injection. DISCUSSION: Intra-articular injection of SVF can be a simple, affordable, and minimally invasive treatment that could serve as an interim option for patients who failed other conservative and arthroscopic options. CONCLUSION: Intra-articular injection of SVF is a safe and effective technique for the management of knee OA. However, comparative Level I studies are needed to support the use of adjuvants with SVF and also to compare the use of SVF (with or without adjuvants) with ADMSCs, PRP, and bone marrow concentrate.

Modulation of inner filter effect of non-conjugated silver nanoparticles on blue emitting ZnS quantum dots for the quantitation of betahistine.

A simple, reliable and efficient fluorescent probe has been developed for the detection and quantitation of betahistine using inner filter effect (IFE) of silver nanoparticles (AgNPs) on zinc sulphide (ZnS) quantum dots. The synthesized ZnS exhibited blue emission at 403 nm which was quenched upon mixing with AgNPs due to intensive localized surface plasmon resonance (LSPR) absorption at 401 nm. The presence of IFE was confirmed by UV-Visible and fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. Addition of betahistine caused aggregation of AgNPs as visualized by the change in colour of nano-suspension. The reduced absorption at LSPR resulted in inhibition of IFE leading to higher fluorescence intensities in the presence of betahistine. Parameters such as pH, incubation time and concentration of AgNPs were suitably optimized. The fluorescence signal (I - I0/I0) responded linearly for betahistine in the concentration range from 0.1 to 10 µM under the optimized experimental conditions. Due to the aggregation of AgNPs, a simple colorimetric approach was also studied for quantitation of betahistine in the range 1.0-20 µM. The limit of detection for fluorescence measurement and colorimetric approach was 0.02 µM and 0.23 µM, respectively. Further, the proposed method exhibited excellent selectivity towards betahistine in presence of several cations, biomolecules such as glucose, uric acid, creatinine, amino acids and several anti-vertigo medications. The method was applied to quantify betahistine from pharmaceutical products and results obtained were in good agreement with the claimed values. The proposed sensor can serve a low cost, selective, sensitive and a precise tool for routine quantitation of betahistine.

Dual Fluorescence-colorimetric Silver Nanoparticles Based Sensor for Determination of Olanzapine: Analysis in Rat Plasma and Pharmaceuticals.

The present work describes a dual-readout assay for the determination of an antipsychotic drug olanzapine using Rhodamine B modified silver nanoparticles (AgNPs). AgNPs, when mixed with Rhodamine B, quenched its fluorescence emission with high quenching efficiency as evident from the Stern Volmer plot. Transmission electron microscopy image and Dynamic Light Scattering histogram of Rhodamine B bound AgNPs showed a stable monodispersed nanosuspension. Addition of olanzapine to Rhodamine B-bound AgNPs resulted in reappearance of fluorescence, which was dependent on the amount of olanzapine added to the system. Besides displacing the surface bound Rhodamine B molecules, it caused aggregation of AgNPs which formed the basis of dual-readout sensor. Several parameters such as pH, reaction time and order of addition of the three components which may influence the analytical signal were studied and optimized. The method was validated for linearity, sensitivity, selectivity, accuracy, precision and recovery. Based on this dual-readout system, linear concentration range was established from 0.05 to 10 µM (fluorescence measurement) and 5.0 to 50 µM (colorimetric response) for olanzapine. The limit of detection (LOD) using fluorescence and colorimetric approach was 0.013 µM and 1.25 µM, respectively. The proposed method showed excellent selectivity for olanzapine in presence of several antipsychotic drugs, cations, sugars and amino acids. Finally, the method was successfully applied to a pharmacokinetic study of olanzapine in rats and also for analyzing pharmaceutical formulations.

Influence of pH and organic modifiers on the dissociation constants of selected drugs using reversed-phase thin-layer chromatography: Comparison with other techniques and computational tools.

Knowledge of the acid-base dissociation constants of drugs is the key to understanding their biopharmaceutical characteristics. In the present work, the effect of pH and organic modifiers (acetonitrile and methanol) was investigated in the determination of dissociation constants (pKa ) of nine representative drugs (atenolol, betahistine, clarithromycin, deferiprone, diclofenac, ibuprofen, metoprolol, naproxen and propranolol) using reversed-phase thin-layer chromatography. Mobile phase consisting of various buffers and methanol-acetonitrile (10, 20, 30, 40, 50 and 60%, v/v) was used to evaluate the retention pattern on reversed-phase plates. Compared with methanol, acetonitrile gave better results for the experimentally determined pKa values by extrapolation to zero organic modifier volume fractions. To assess the effectiveness of the developed method the results were correlated using principal component analysis and hierarchical cluster analysis. The calculated values of the aqueous dissociation constant were compared with those reported previously using potentiometry and capillary electrophoresis and also with different computational platforms like ACD/Lab, ChemAxon and Jchem calculator. The results obtained by the RPTLC method were in good agreement with potentiometric methods for pKa determination.

Densitometry and indirect normal-phase HPTLC-ESI-MS for separation and quantitation of drugs and their glucuronide metabolites from plasma.

The present work describes novel methods using densitometry and indirect or off-line high performance thin-layer chromatography-mass spectrometry (HPTLC-MS) for the simultaneous detection and quantification of asenapine, propranolol and telmisartan and their phase II glucuronide metabolites. After chromatographic separation of the drugs and their metabolites the analytes were scraped, extracted in methanol and concentrated prior to mass spectrometric analysis. Different combinations of toluene and methanol-ethanol-n-butanol-iso-propanol were tested for analyte separation and the best results were obtained using toluene-methanol-ammonia (6.9:3.0:0.1, v/v/v) as the elution solvent. All of the drug-metabolite pairs were separated with a homologous retardation factor difference of ≥22. The conventional densitometric approach was also studied and the method performances were compared. Both of the approaches were validated following the International Conference on Harmonization guidelines, and applied to spiked human plasma samples. The major advantage of the TLC-MS approach is that it can provide much lower limits of detection (1.98-5.83 pg/band) and limit of quantitation (5.97-17.63 pg/band) with good precision (˂3.0% coefficient of variation) compared with TLC-densitometry. The proposed indirect HPTLC-MS method is simple yet effective and has tremendous potential in the separation and quantitation of drugs and their metabolites from biological samples, especially for clinical studies.

Influence of organic modifier and separation modes for lipophilicity assessment of drugs using thin layer chromatography indices.

Lipophilicity constitutes one of the most important physicochemical properties in the design and development of drug molecules. In the present work thin layer chromatography (TLC) has been utilized to evaluate lipophilicity of 11 representative drugs, which included six proton pump inhibitors (omeprazole, pantoprazole, rabeprazole, lansoprazole, ilaprazole, and tenatoprazole), an anti-vertigo drug, betahistine, nonsteroidal anti-inflammatory drug, ibuprofen, anti-malarial drug, atovaquone, an anti-HIV agent, atazanavir and a hormonal drug, calcitriol. Normal as well as reversed-phase separation modes were evaluated to study the effect of different organic modifiers for the estimation of lipophilicity. The quantitative descriptor of lipophilicity, the partition coefficient (logP) was estimated by suitably optimizing the solvent systems for both the modes. The best mobile phase pairs for NPTLC and RPTLC were toluene-acetonitrile and water-methanol respectively. Principal component analysis, hierarchical cluster analysis, as well as non-parametric methods like sum of ranking differences and generalized pair wise correlation revealed the dominant pattern in the data. The results obtained from both the separation modes were comparable and were in good agreement with the computational data for all the drugs.

Design of experiment assisted concurrent enantioseparation of bupropion and hydroxybupropion by high-performance thin-layer chromatography.

A simple and efficient high-performance thin-layer chromatographic method was developed for chiral separation of rac-bupropion (BUP) and its active metabolite rac-hydroxybupropion (HBUP). Design of experiment (DoE)-based optimization was adopted instead of a conventional trial-and-error approach. The Box-Behnken design surface response model was used and the operating variables were optimized based on 17 trials design. The optimized method involved impregnation of chiral reagent, L(+)-tartaric acid, in the stationary phase with simultaneous addition in the mobile phase, which consisted of acetonitrile : methanol : dichloromethane : 0.50% L-tartaric acid (6.75:1.0:1.0:0.25, v/v/v/v). Under the optimized conditions, the resolution factor between the enantiomers of BUP and HBUP was 6.30 and 9.26, respectively. The limit of detection and limit of quantitation for (R)-BUP, (S)-BUP, (R,R)-HBUP, and (S,S)-HBUP were 9.23 and 30.78 ng spot-1 , 10.32 and 34.40 ng spot-1 , 12.19 and 40.65 ng spot-1 , and 14.26 and 47.53 ng spot-1 , respectively. The interaction of L-tartaric acid with analytes and their retention behavior was thermodynamically investigated using van't Hoff's plots. The developed method was validated as per the International Conference on Harmonization guidelines. Finally, the method was successfully applied to resolve and quantify the enantiomeric content from marketed tablets as well as spiked plasma samples.

Surface plasmon resonance based selective and sensitive colorimetric determination of azithromycin using unmodified silver nanoparticles in pharmaceuticals and human plasma.

In this article we report a novel method for colorimetric sensing and selective determination of a non-chromophoric drug-azithromycin, which lacks native absorbance in the UV-Visible region using unmodified silver nanoparticles (AgNPs). The citrate-capped AgNps dispersed in water afforded a bright yellow colour owing to the electrostatic repulsion between the particles due to the presence of negatively charged surface and showed surface plasmon resonance (SPR) band at 394nm. Addition of positively charged azithromycin at a concentration as low as 0.2µM induced rapid aggregation of AgNPs by neutralizing the negative charge on the particle surface. This phenomenon resulted in the colour change from bright yellow to purple which could be easily observed by the naked eye. This provided a simple platform for rapid determination of azithromycin based on colorimetric measurements. The factors affecting the colorimetric response like pH, volume of AgNPs suspension and incubation time were suitably optimized. The validated method was found to work efficiently in the established concentration range of 0.2-100.0µM using two different calibration models. The selectivity of the method was also evaluated by analysis of nanoparticles-aggregation response upon addition of several anions, cations and some commonly prescribed antibiotics. The method was successfully applied for the analysis of azithromycin in pharmaceuticals and spiked human plasma samples with good accuracy and precision. The simplicity, efficiency and cost-effectiveness of the method hold tremendous potential for the analysis of such non-chromophoric pharmaceuticals.

Combining simplicity with cost-effectiveness: Investigation of potential counterfeit of proton pump inhibitors through simulated formulations using thin-layer chromatography.

A simple, accurate and precise high-performance thin-layer chromatographic method has been developed and validated for the analysis of proton pump inhibitors (PPIs) and their co-formulated drugs, available as binary combination. Planar chromatographic separation was achieved using a single mobile phase comprising of toluene: iso-propranol: acetone: ammonia 5.0:2.3:2.5:0.2 (v/v/v/v) for the analysis of 14 analytes on aluminium-backed layer of silica gel 60 FG254. Densitometric determination of the separated spots was done at 290nm. The method was validated according to ICH guidelines for linearity, precision and accuracy, sensitivity, specificity and robustness. The method showed good linear response for the selected drugs as indicated by the high values of correlation coefficients (≥0.9993). The limit of detection and limit of quantiation were in the range of 6.9-159.2ng/band and 20.8-478.1ng/band respectively for all the analytes. The optimized conditions afforded adequate resolution of each PPI from their co-formulated drugs and provided unambiguous identification of the co-formulated drugs from their homologous retardation factors (hRf). The only limitation of the method was the inability to separate two PPIs, rabeprazole and lansoprazole from each other. Nevertheless, it is proposed that peak spectra recording and comparison with standard drug spot can be a viable option for assignment of TLC spots. The method performance was assessed by analyzing different laboratory simulated mixtures and some marketed formulations of the selected drugs. The developed method was successfully used to investigate potential counterfeit of PPIs through a series of simulated formulations with good accuracy and precision.

Study of morbidity pattern among salt workers in marakkanam, Tamil Nadu, India.

BACKGROUND: Salt workers are exposed to occupational hazards like contact with salt crystals and brine, physical stress, sunlight and glare due to sunlight reflected by salt crystals. Very few studies have documented the morbidity among the salt workers. AIM: To assess the morbidity pattern among salt workers in Marakkanam, Tamil Nadu, India. MATERIALS AND METHODS: A community based cross-sectional study was undertaken in 4 randomly selected salt worker villages. Three hundred thirty one salt workers were reached by a house-to-house survey during April 2010 to March 2011. Demographic data was collected; clinical examination was conducted using a predesigned and pretested questionnaire. A pilot study was conducted to estimate the prevalence of morbidity before initiating the study. The data was analyzed using SPSS Version 11.5. Chi-square test and odds ratios (OR) with 95% confidence intervals (CI) were calculated to determine the association of morbidity levels with various factors. RESULTS: Of the 331 salt workers in the study, 58% were females, mean age was 41.9 ± 10.8 y. Eighty seven percent salt workers had some or other morbidity. The observed morbidities include clinical pallor (44.4%), ocular morbidities including cataract, pterygium, conjunctivitis, pingecula and corneal ulcer (42%), caries teeth (41.7%), hypertension (23.3%), underweight (19.3%), goiter (19%), obesity (14.8%) and dermal conditions including dermatitis, thickening of palm and sole, tinea unguum, follicultitis (9.1%). The presence of morbidity did not show any significant association with increase in age, gender, duration of employment or the type of salt work involved with. However, the lower the education level, the higher is the morbidity level among salt workers (OR = 5.23, 95% CI= 2.07 to 13.21). CONCLUSION: Morbidity among salt workers is high. Intervention programs are needed to alleviate the health problems in the salt workers.

Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLC-MS/MS.

A simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards (ISs). Plasma samples were prepared using solid phase extraction and chromatographic separation was performed on UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm) column. The method was established over a concentration range of 0.5-1000 ng/mL for cilostazol and 0.5-500 ng/mL for 3,4-dehydro cilostazol. Intra- and inter-batch precision (% CV) and accuracy for the analytes were found within 0.93-1.88 and 98.8-101.7% for cilostazol and 0.91-2.79 and 98.0-102.7% for the metabolite respectively. The assay recovery was within 95-97% for both the analytes and internal standards. The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in 30 healthy subjects.

Manipulating ratio spectra for the spectrophotometric analysis of diclofenac sodium and pantoprazole sodium in laboratory mixtures and tablet formulation.

OBJECTIVE: Three sensitive, selective, and precise spectrophotometric methods based on manipulation of ratio spectra, have been developed and validated for the determination of diclofenac sodium and pantoprazole sodium. MATERIALS AND METHODS: The first method is based on ratio spectra peak to peak measurement using the amplitudes at 251 and 318 nm; the second method involves the first derivative of the ratio spectra (Δλ = 4 nm) using the peak amplitudes at 326.0 nm for diclofenac sodium and 337.0 nm for pantoprazole sodium. The third is the method of mean centering of ratio spectra using the values at 318.0 nm for both the analytes. RESULTS: All the three methods were linear over the concentration range of 2.0-24.0 µ g/mL for diclofenac sodium and 2.0-20.0 µg/mL for pantoprazole sodium. The methods were validated according to the ICH guidelines and accuracy, precision, repeatability, and robustness are found to be within the acceptable limit. The results of single factor ANOVA analysis indicated that there is no significant difference among the developed methods. CONCLUSIONS: The developed methods provided simple resolution of this binary combination from laboratory mixtures and pharmaceutical preparations and can be conveniently adopted for routine quality control analysis.