Fluoride content and labelling of toothpastes marketed in India.

OBJECTIVE: To enumerate the fluoride content and labelling practices of toothpastes marketed in India and to determine if the content is in accordance with the information provided on the packaging. METHOD: In vitro analysis of total and free available fluoride in 5 adult and 5 children's fluoride toothpastes in India using fluoride ion electrode. Information on the tube and carton was checked to assess the labelling. RESULTS: The mean Total Fluoride concentrations (TF) in the toothpastes labelled 1,000 ppm, 500ppm and 458 ppm were 1,000, 500 and 449mg/L (sd values 3, 5 and 4mg/L) respectively. The toothpastes' Total Soluble Fluoride (TSF) concentration was generally slightly less than the TF concentration. Overall mean percentage of TSF concentration was 94% sd 9%. The mean percentage of TSF concentration in SMFP (sodium monofluorophosphate)/CaCO3 (calcium carbonate) containing toothpastes was 86% sd 16% while that in NaF (sodium fluoride)/Si (silica) based toothpastes was 98% sd 1% and 95% sd 1% in the remaining toothpastes with unknown abrasive. NaF/Si based toothpastes had more TSF concentration than the others (p<0.05). All the information required by the Indian regulations was shown on all 10 toothpastes. CONCLUSION: The available fluoride content of one of the ten toothpastes was substantially less than the total fluoride content. Although the toothpastes were labelled following the guidelines of the regulatory body of India, 3 of the 10 failed to mention the abrasive present.

Cost savings with a new screening algorithm for pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is now standard care in this disease. The existing Australian Scleroderma Interest Group algorithm (ASIGSTANDARD ) is based on transthoracic echocardiography (TTE) and pulmonary function tests (PFT). Recently, ASIG has derived and validated a new screening algorithm (ASIGPROPOSED ) that incorporates N-terminal pro-B-type natriuretic peptide level together with PFT in order to decrease reliance on TTE, which has some limitations. Right heart catheterisation (RHC) remains the gold standard for the diagnosis of PAH in patients who screen 'positive'. AIM: To compare the cost of PAH screening in SSc with ASIGSTANDARD and ASIGPROPOSED algorithms. METHODS: We applied both ASIGSTANDARD and ASIGPROPOSED algorithms to 643 screen-naïve SSc patients from the Australian Scleroderma Cohort Study (ASCS), assuming a PAH prevalence of 10%. We compared the costs of screening, the number of TTE required and both the total number of RHC required and the number of RHC needed to diagnose one case of PAH, and costs, according to each algorithm. We then extrapolated the costs to the estimated total Australian SSc population. RESULTS: In screen-naïve patients from the ASCS, ASIGPROPOSED resulted in 64% fewer TTE and 10% fewer RHC compared with ASIGSTANDARD , with $1936 (15%) saved for each case of PAH diagnosed. When the costs were extrapolated to the entire Australian SSc population, there was an estimated screening cost saving of $946 000 per annum with ASIGPROPOSED , with a cost saving of $851 400 in each subsequent year of screening. CONCLUSIONS: ASIGPROPOSED substantially reduces the number of TTE and RHC required and results in substantial cost savings in SSc-PAH screening compared with ASIGSTANDARD .

Prospects for improving outcomes in systemic sclerosis-related pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). Approximately one in 10 will develop PAH during their lifetime. These patients have a worse prognosis than those with PAH due to other causes. The most common clinical feature of SSc-PAH in the early stages is non-specific exercise intolerance that can be erroneously attributed to other manifestations of SSc. Screening provides an opportunity for early identification of SSc-PAH and prompt initiation of therapies with the potential to improve quality of life and survival. International guidelines recommend annual transthoracic Doppler echocardiography (TTE), but TTE has limitations. The tricuspid regurgitant jet required for estimating the systolic pulmonary artery pressure is absent in up to 39% of patients, including a proportion with PAH. This has prompted a move to new screening algorithms that are less dependent on TTE. Not all pulmonary hypertension (PH) in patients with SSc is PAH. Other causes include PH secondary to left heart disease, interstitial lung disease-related PH, chronic thromboembolic PH and pulmonary veno-occlusive disease. With the advent of evidence-based therapies, including newer agents such as macitentan, riociguat and selexipag, the establishment of centres with expertise in PAH and the focus on early detection, there has been considerable improvement in survival. The role of anti-coagulation for SSc-PAH has been the subject of a recent meta-analysis of nine observational studies that suggests it may confer a survival benefit, but to date, there have been no randomised controlled trials to confirm this.

The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis.

OBJECTIVES: To determine the prevalence and correlates of antiphospholipid antibodies (APLA) in systemic sclerosis (SSc). METHODS: Nine hundred and forty SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical manifestations were defined as present, if ever present from SSc diagnosis. Logistic regression analysis was used to determine the associations of APLA. RESULTS: One or more types of APLA were present in 226 (24.0%) patients. Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA-IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA-IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI: 1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08-5.27, p=0.031). There was no association between APLA and SSc disease subtype, peak skin score, presence of other autoantibodies, mortality or other disease manifestations. CONCLUSIONS: The association of APLA with PAH, ILD, ILD-PH, Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features.

Performance of screening algorithms in systemic sclerosis-related pulmonary arterial hypertension: a systematic review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). There is emerging evidence that screening may enable the earlier detection and treatment of SSc-PAH, and thereby improve survival. AIMS: We undertook a systematic review to evaluate the performance of current screening algorithms in SSc-PAH. METHODS: We searched the Medline and EMBASE databases to 31 March 2012. We selected studies if they applied a screening algorithm to consecutively enrolled SSc patients not known to have PAH; SSc-PAH had to be confirmed on right heart catheterisation (RHC). The performance of each screening algorithm and the methodological quality of each study was evaluated. RESULTS: Nine studies met the inclusion criteria with a total intent-to-screen population of 3504 participants. In studies of patients with prevalent disease, the positive predictive value (PPV) of screening for PAH was 20.4-87.0%. In studies of patients with incident disease, the PPV of screening for PAH was 20.0-30.7%. The PPV of algorithms using echocardiography alone, or in combination with other tests, was comparable. No study enabled an accurate determination of negative predictive value, sensitivity or specificity of the screening algorithm as only patients who screened positive underwent confirmatory testing with RHC. The optimal timing and frequency of repeat screening is unknown. CONCLUSION: The low to moderate PPV of current screening algorithms, coupled with the inability to determine accurately the negative predictive value, sensitivity and specificity, suggests that there is a need to validate further these algorithms before making recommendations regarding screening for SSc-PAH.

The angiotensin-converting enzyme gene insertion/deletion polymorphism in Indian patients with vitiligo: a case-control study and meta-analysis.

BACKGROUND: Vitiligo is a common, acquired, idiopathic depigmenting skin disorder. Although the exact pathogenesis remains unknown, genetic susceptibility and autoimmune responses play a role in vitiligo development. Previous studies have suggested that the D allele of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with vitiligo in Indians and Koreans. Furthermore, significantly higher serum ACE levels have been demonstrated in patients with some autoimmune and autoinflammatory disorders. OBJECTIVES: The objectives were to investigate any association between the ACE I/D polymorphism and vitiligo susceptibility in an Indian population, and to compare serum ACE levels in patients with vitiligo and healthy subjects. METHODS: The ACE I/D genotypes of 79 patients with vitiligo and 100 normal individuals were determined by polymerase chain reaction amplification. A meta-analysis was done to compare the distribution of the ACE I/D alleles and genotypes in the current and three previous studies. Serum ACE levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: A significant increase in the frequency of the ACE I/D D allele was evident in patients with vitiligo in both the case-control study [P=0·005; odds ratio (OR) 1·87; 95% confidence intervals (CI) 1·22-2·85] and the meta-analysis (P=0·044; OR 1·44; 95% CI 1·01-2·06). Serum ACE levels were significantly increased in patients with vitiligo compared with healthy subjects (P<0·0001). CONCLUSIONS: In agreement with earlier reports, the ACE I/D D allele is associated with vitiligo susceptibility in the Indian population. The significantly elevated serum ACE levels in our cohort of patients with vitiligo concur with those previously found in patients with some other autoimmune diseases.

Vitiligo patients from India (Mumbai) show differences in clinical, demographic and autoantibody profiles compared to patients in western countries.

BACKGROUND: Vitiligo is a common, idiopathic skin disorder characterized by depigmented skin due to the loss of cutaneous melanocytes. Several studies have reported the clinical and demographic characteristics of Indian vitiligo patients, however, none has characterized their antibody profiles. OBJECTIVE: To establish the clinical, demographic and serological details of a population of vitiligo patients from Mumbai, India, and to evaluate the data for any associations between clinical presentations and the occurrence of antibody responses. METHODS: Vitiligo patients (n = 79) were recruited to the study and their clinical and demographic details recorded. Serum antibodies, including those against melanocyte-specific antigens, thyroid antigens and keratinocytes, were evaluated. RESULTS: The prevalence of vitiligo was independent of sex, and non-segmental vitiligo was the most common form of the disease occurring in 65% of the patients. Patients with segmental vitiligo (mean age = 14.4 ± 4.6 years) presented at a younger age than those with non-segmental disease (mean age = 32.5 ± 17.8 years). Personal and family histories of other autoimmune diseases occurred in 3% and 8% of patients, respectively. Antibodies were detected against tyrosinase, tyrosine hydroxylase, thyroid peroxidase, thyroglobulin and keratinocytes at frequencies of 11%, 22%, 18%, 24% and 27%, respectively. Overall, antibodies were more common in patients with non-segmental vitiligo (50-67%) than in those with segmental disease (0-17%), and were detected more frequently in patients with shorter disease durations (<10 years). CONCLUSION: Our study provides novel information relative to the clinical details, demographic features and serological parameters of a population of vitiligo patients from Mumbai, India. Important distinctions from similar surveys conducted in European patients were evident such as an infrequency of family history, a low prevalence of clinical autoimmune disease, and an absence of particular antibody specificities. These differences may have a bearing on the pathogenesis and course of the disease in Indian patients.

Development and characterisation of thermo reversible mucoadhesive moxifloxacin hydrochloride in situ ophthalmic gel.

A sustain release thermo reversible in situ gel of Moxifloxacin Hydrochloride using mucoadhesive polymer was prepared. Mucoadhesive polymer was used to obtain an ophthalmic delivery system with improved mechanical and mucoadhesive properties that will provide prolong retention time for treatment of ocular diseases. Developed formulations were evaluated for drug-excipient compatibility study, pH, Clarity, Gelation temperature study, Mucoadhesion properties and in-vitro release studies. Drug-excipient compatibility study was performed by FTIR technique. The individual IR spectra of the pure drug and polymers as well as the combination spectra of the drug and polymer were taken, which indicate no interaction between Moxifloxacin and polymers when compared with infrared spectrum of pure drug as all functional group frequencies were present. The values of other parameters obtained were in acceptable range. In vitro release tests revealed that 98% drug was released from the in situ gel containing 0.5% and 1.00% HPMC in 12 hr. provides prolonged release.

Optimization of the experimental parameters of fluticasone propionate microparticles for pulmonary delivery using a box behenken design.

The objective of this study was to examine extensively the influences of formulation and process variables on the microparticles. The microparticles were generated by the spray-drying technique using polymer chitosan, mannitol along with L-leucine. The effects of various experimental parameters such as polymer concentration, inlet temperature, and feed flow rate on particle size and production yields were evaluated by means of experimental box-behnken design. Multiple regression analysis was carried out and response surfaces were obtained. Optimized formulation and check points batches were selected by feasibility and grid search. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the production yield. Feed flow rate impact on particle size. Results showed that spray drying technique yield 985 to 4060 nm indicate micro size range and production yield was found in between 27.01-52.96%. The selection of appropriate parameters yielded spray-dried microparticles characterized by narrow dimensional distribution. In our present work, prepared microparticles using the spray-drying technique and systematically estimated their feasibility for the pulmonary delivery of microparticles by careful investigations of their characteristics and aerosolization properties. Spray drying technique yield optimum size for deposition beyond the narrow airway into the alveoli and suitable for respiratory deposition.

Effects of spray drying conditions on the physicochemical properties of the Tramadol-Hcl microparticles containing Eudragit(®) RS and RL.

The preparation of Tramadol-HCL spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug-polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain tramadol spray-dried microspheres using the Eudragit(®) RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. The effects of matrix composition on microparticle properties were characterized by Laser Light scattering, differential scanning calorimetry (DSC), X-ray diffraction study, FT-infrared and UV-visible spectroscopy. The spray-dried microparticles were evaluated in terms of shape (SEM), size distribution (Laser light scattering method), production yield, drug content, initial drug loding and encapsulation efficiency. The results of X-ray diffraction and thermal analysis reveals the conversion of crystalline drug to amorphous. FTIR analysis confirmed the absence of any drug polymer interaction. The results indicated that the entrapment efficiency (EE), and product yield were depended on polymeric composition and polymeric ratios of the microspheres prepared. Tramadol microspheres based on Eudragit(®) blend can be prepared by spray-drying and the nebulization parameters do not influence significantly on particle properties.

Development and in vivo evaluation of silver sulfadiazine loaded hydrogel consisting polyvinyl alcohol and chitosan for severe burns.

A new Hydrogel containing silver Sulfadiazine (SSD) was developed for enhanced burns wound healing. The hydrogel was prepared by cross-linking of PVA and Chitosan by freeze thawing method. Their gel properties, moisture retaining capacity, fluid uptake capacity, in vitro release study, in vivo burn healing effect were evaluated. Chitosan and PVA cross linking decreased gel fraction upto 70% determined the good gel properties. This cross linked hydrogel increased the Swelling ratio and Water vapour transmission rate (WVTR) which provides the sustained release of drug and moist environment for healing respectively. The hydrogel containing 7.5% of PVA, 0.75% of chitosan found to have increased gel strength, higher water vapour transmission rate and fluid uptake capacity suitable for faster healing of burns. This hydrogel also sustained the release of 1% SSD required for longer antimicrobial activity and found better in vivo burn healing capacity as compared to marketed preparation. Thus hydrogel containing 7.5% of PVA, 0.75% of chitosan and 1% SSD is a potential burns dressing with better gel properties and excellent burns healing capacity.

Evaluation of bioequivalence of two oral formulations of olanzapine.

Olanzapine is an atypical antipsychotic drug, used for the management of schizophrenia and for the treatment of moderate to severe mania associated with bipolar disorder. The objective of the present randomised, crossover study was to compare the bioavailability of olanzapine 10 mg/5 ml powder for oral suspension with olanzapine 10 mg orally disintegrating tablet. Eighteen healthy male volunteers were randomly assigned to crossover, single-dose treatment regimens. Serial blood samples were collected, and plasma concentrations of olanzapine were analysed using the LC-MS/MS technique. Pharmacokinetic parameters and bioequivalence limits were calculated using non-compartmental methods. Average C(max) following administration of the single 10 mg disintegrating tablet formulation and 10 mg/5 ml suspension were 14.47±4.25 ng/ml and 13.56±3.99 ng/ml respectively. Corresponding median T(max) were 5.0 h and 6.0 h, respectively. The average AUC(0-t) values and AUC(0-inf) values were similar following each of the olanzapine preparations. Overall, the 90% Confidence Interval for the intra-individual ratios of the log-transformed C(max) and AUC values of the two formulations were within the bioequivalence interval of 80-125%. The study has demonstrated the bioequivalence of the 10 mg tablet and the 10 mg/5 ml oral suspension of olanzapine.

DNA cleavage, binding and intercalation studies of drug-based oxovanadium(IV) complexes.

The complexes of oxovanadium(IV) with ciprofloxacin and various uni-negative bidentate ligands have been prepared and their structure investigated using spectral, physicochemical and elemental analyses. The viscosity measurement suggest that the complexes bind to DNA by intercalation. The DNA binding efficacy was determined using absorption titration to obtain the binding constant (K(b)). The DNA cleavage efficacy was determined using gel electrophoresis. The DNA binding and cleavage efficacy were increased in the complexes relative to the parental ligands and metal salts. Antibacterial activity has been assayed against two Gram((- ve)) i.e. Escherichia coli, Pseudomonas aeruginosa and three Gram((+ ve)) Staphylococcus aureus, Bacillus subtilis, Serratia marcescens microorganisms using the doubling dilution technique. The results show a significant increase in antibacterial activity in the complexes compared with parental ligands and metal salts.

Variation in metabolites constituent in leaves of downy mildew resistant and susceptible genotypes of pearl millet.

In the present investigation biochemical characterization of pearl millet genotypes was carried at pre (45 DAS) and post-infection (57 DAS i.e. 7 days after infection) stage. Total soluble sugar was greater at pre infection than post infection in downy mildew resistant and susceptible genotypes of pearl millet. Total soluble sugar decreased in all genotypes at 7 days after infection (d.a.i.) except in 7042 S in which it increased 4.6 %. However, total soluble sugar was 2-3 folds more in highly susceptible genotypes (J-2296 and 7042 S) compared to resistant genotypes at 7 d.a.i. but it was decreased as compared to pre infection. The total amino acid content of all genotypes whether resistant or susceptible, finally increased as a result of infection. Moreover, susceptible genotypes registered 2-2.5 % higher amino acid, whereas resistant genotypes possessed 6.2-76 % higher amino acid than their constitutive level. Total chlorophyll and carotenoids content did not show any clear cut difference in resistant and susceptible genotypes at pre-infection stage. However, at post-infection stage a significant decrease in chlorophyll and carotenoids content occurred in susceptible genotypes from pre-infection. Amino acid profiling through HPTLC showed sulphur containing amino acids were higher in resistant genotypes.

Response surface methodology to optimize the nutritional parameters for enhanced production of jasmonic acid by Lasiodiplodia theobromae.

AIMS: To find out the cumulative effect of the nutritional parameters and to enhance the production of jasmonic acid (JA) in static fermentation by Lasiodiplodia theobromae using response surface methodology (RSM). METHOD AND RESULTS: Malt extract, sucrose, NaNO(3) and MgSO(4).7H(2)O were analysed by a 30-trial central composite design using RSM for optimizing their concentrations in the medium and the effect of their mutual interaction on JA production. Sucrose and NaNO(3) were found highly significant in influencing the JA production. Malt extract and MgSO(4).7H(2)O showed an effect on the JA production in interaction with other variables. When the optimum values of the parameters obtained through RSM (19.95 g l(-1) malt extract, 50 g l(-1) sucrose, 7.5 g l(-1) NaNO(3) and 3.51 g l(-1) MgSO(4).7H(2)O) were applied, 32% increase in JA production (299 mg l(-1)) was observed in comparison with 225 mg l(-1) of JA produced with same media components not analysed by RSM and subsequently validated the statistical model. CONCLUSIONS: Increase in JA production was achieved by optimizing the nutritional parameters. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of using RSM for optimizing a medium for JA production. It resulted in an increase in JA production without augmentation of costly additives.

The impact of a geriatrics evaluation and management unit compared to standard care in a community teaching hospital.

A prospective, controlled trial was initiated to determine whether an acute inpatient geriatrics unit located in a community-based teaching hospital provides better care for frail elderly patients at less cost than conventional medical-surgical units.

Perceiving individuals and groups: expectancies, dispositional inferences, and causal attributions.

Two experiments investigated differences in forming impressions of individual and group targets. Experiment 1 showed that when forming an impression of an individual, perceivers made more extreme trait judgments, made those judgments more quickly and with greater confidence, and recalled more information than when the impression target was a group. Experiment 2 showed that when participants were forming an impression of an individual, expectancy-inconsistent behaviors spontaneously triggered causal attributions to resolve the inconsistency; this was not the case when the impression target was a group. Results are interpreted as reflecting perceivers' a priori assumptions of unity and coherence in individual versus group targets.