Formulation of sildenafil citrate loaded nasal microsphers: An in vitro, ex vivo characterization

The aim of the present study was to prepare gellan gum microspheres of Sildenafil citrate, for intranasal delivery to avoid the first pass metabolism. The microspheres were prepared using spray drying method. The microspheres were evaluated for characteristics like particle size, incorporation efficiency, swelling ability, zeta potential, in-vitro mucoadhesion, ex-vivo mucoadhesion, thermal analysis, XRD study and in-vitro drug release. Treatment of in-vitro data to different kinetic equations indicated diffusion controlled drug delivery from gellan gum microspheres. The results of DSC and XRD studies revealed the molecular amorphous dispersion of Sildenafil citrate into the gellan gum microspheres. Microspheres so prepared were discrete, bulky, free flowing and showed an average encapsulation efficiency ranging from 95-98%. The formulation exhibited a good mucoadhesive strength which was determined in in vitro conditions through falling film technique and was compared with ex vivo studies. The microspheres so prepared also exhibited a good swelling index which confirmed the strong mucoadhesive property of the formulation.Keywords: Gellan gum, Microsperes, Spray drying, Sildinafil citrate, Nasal delivery

Formulation of sildenafil citrate loaded nasal microsphers: An in vitro, ex vivo characterization

The aim of the present study was to prepare gellan gum microspheres of Sildenafil citrate, for intranasal delivery to avoid the first pass metabolism. The microspheres were prepared using spray drying method. The microspheres were evaluated for characteristics like particle size, incorporation efficiency, swelling ability, zeta potential, in-vitro mucoadhesion, ex-vivo mucoadhesion, thermal analysis, XRD study and in-vitro drug release. Treatment of in-vitro data to different kinetic equations indicated diffusion controlled drug delivery from gellan gum microspheres. The results of DSC and XRD studies revealed the molecular amorphous dispersion of Sildenafil citrate into the gellan gum microspheres. Microspheres so prepared were discrete, bulky, free flowing and showed an average encapsulation efficiency ranging from 95-98%. The formulation exhibited a good mucoadhesive strength which was determined in in vitro conditions through falling film technique and was compared with ex vivo studies. The microspheres so prepared also exhibited a good swelling index which confirmed the strong mucoadhesive property of the formulation.Keywords: Gellan gum, Microsperes, Spray drying, Sildinafil citrate, Nasal delivery

Niska masa szkieletu ważnym czynnikiem predykcyjnym osteoporozy u mężczyzn zakażonych wirusem HIV w Indiach

Introduction: This study evaluated prevalence and predictors of osteoporosis and sarcopenia in men with HIV. Material and methods: 220 men with HIV were screened, of which 115 men, 30–50 years-age, having at least 1-year follow-up, underwent hormonal and DEXA analysis. 40 controls were also evaluated. Results: Males with HIV had significantly lower BMD and Z-scores at all sites. Osteoporosis was diagnosed in 64.35%; commonest site being radius total (49.56%), followed by radius 33% (45.21%), radius ultra distal (36.52%), lumbar spine (19.13%), neck of femur (17.39%), total femur and greater trochanter (7.82% each). HIV patients had significantly lower fat mass (FM), lean mass (LM), total fat percent, bone mineral content, gynoid fat, percent skeletal muscle mass (PSMM). Men with osteoporosis had higher use of anti retroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS), tuberculosis, lower FM, LM and PSMM. Logistic regression revealed PSMM, age and delta (Δ) CD4 count (change in CD4 count after 6–12 months of ART, compared to pre-ART) were best predictors of osteoporosis. Greater PSMM was associated with decreased osteoporosis, without adjusting for any variable (Model-1), adjusting for disease duration, tuberculosis and IRIS (Model-2), and model-2 plus gonadotropins and sex steroids (Model-3). Greater ΔCD4 count and age were associated with increased osteoporosis after adjusting for different models. Sarcopenia was observed in 40% men and none in controls. Conclusions: Men with decreased skeletal mass, age, severe immune dysfunction at diagnosis, having rapid increase in CD4 count following ART and IRIS have higher risk of osteoporosis in the long run.Introduction: This study evaluated prevalence and predictors of osteoporosis and sarcopaenia in men with HIV. Material and methods: A total of 220 men with HIV were screened, of which 115 men, 30–50 years-age, having at least one-year follow-up, underwent hormonal and DEXA analysis. Forty controls were also evaluated. Results: Males with HIV had significantly lower BMD and Z-scores at all sites. Osteoporosis was diagnosed in 64.35%, the common­est site being radius total (49.56%), followed by radius 33% (45.21%), radius ultra distal (36.52%), lumbar spine (19.13%), neck of femur (17.39%), and total femur and greater trochanter (7.82% each). HIV patients had significantly lower fat mass (FM), lean mass (LM), total fat percentage, bone mineral content, gynoid fat, and percentage skeletal muscle mass (PSMM). Men with osteoporosis had higher use of anti-retroviral therapy (ART), immune reconstitution inflammatory syndrome (IRIS), tuberculosis, and lower FM, LM, and PSMM. Logistic regression revealed that PSMM, age, and delta (Δ) CD4 count (change in CD4 count after 6–12 months of ART, compared to pre-ART) were the best predictors of osteoporosis. Greater PSMM was associated with decreased osteoporosis, without adjusting for any variable (Model-1), adjusting for disease duration, tuberculosis and IRIS (Model-2), and model-2 plus gonadotropins and sex steroids (Model-3). Greater ΔCD4 count and age were associated with increased osteoporosis after adjusting for different models. Sarcopaenia was observed in 40% of men and in none of the controls. Conclusions: Men with decreased skeletal mass, age, severe immune dysfunction at diagnosis, having rapid increase in CD4 count fol­lowing ART and IRIS have higher risk of osteoporosis in the long run. Wnioski: Mężczyźni z obniżoną masą szkieletu, w starszym wieku i z ciężkimi niedoborami immunologicznymi w czasie rozpoznania, u których następuje gwałtowny wzrost liczby limfocytów CD4 po ART i IRIS, cechują się wyższym ryzykiem osteoporozy w perspektywie długoterminowej

Glycaemic and weight-loss outcomes of graded doses of canagliflozin in type 2 diabetes — a real-world study

Background. Costs are the most important cause of therapeutic non-compliance. Half canagliflozin (CANA)–300 tablet has lowest cost/mg among all CANA preparations; data are unavailable on efficacy of half CANA-300. This study evaluated weight loss and glycaemic outcomes of 100 mg versus 150 mg versus 300 mg of canagliflozin as part of standard therapy.Methods. Data, retrospectively captured from medical records of two centres in Delhi for patients > 35 years with type-2 diabetes (T2DM), and on canagliflozin, having > 6 months follow-up, were analysed. Patients were in 3-groups depending on canagliflozin dosage: Group 1 on canagliflozin 100 mg/day (1 tablet CANA-100), Group-2 on canagliflozin 150 mg/day (half tablet CANA-300), and Group 3 on canagliflozin 300 mg/day (1 tablet CANA-300). Primary endpoints were glycaemicefficacy and weight-loss.Results. From 3,569 records evaluated, 1,232 people with T2DM on canagliflozin were screened; data from 528 individuals analysed (257, 138 and 133 in Groups: 1, 2 and 3 respectively). People in all three groups were comparable with regards to sex, T2DM duration, glycated haemoglobin (HbA1c), haemoglobin, creatinine, lipids, albuminuria and medications. Group-2 patients were youngest and had highest BMI. Following 6-months, both absolute and percent weight-loss was significantly higher in Group-2 (–3.5 kg [–6.60–0.00]; –3.62%), followed by Group-3 (–3.0 kg [–5.3 to –0.8]; –3.33%), and lowest in Group-1 (–1.05 kg [–2.85 to –0.17]; –1.31%) (P = 0.002 and 0.014, respectively). Glycaemic efficacy was comparable among groups.Conclusion. Half CANA-300 tablet has comparable glycaemic efficacy and weight-loss compared to single CANA-300 tablet, but superior weight-loss compared to CANA-100

Post-traumatic extensive scalp ulceration: A diagnostic and management challenge!

Dissecting cellulitis of scalp (DCS) is an uncommon inflammatory dermatosis, which can be difficult to diagnose in the absence of concomitant cutaneous markers. We present an interesting case of DCS in a 60-year-old male, with an onset after blunt trauma to head. The progression was fast and diagnosis could be achieved on multiple biopsies only. The response to therapy with a combination of oral isotretinoin and intralesional triamcinolone acetonide injections is highlighted in this difficult to treat dermatoses

Organic acids and root exudates of Brachypodium distachyon: effects on chemotaxis and biofilm formation of endophytic bacteria

Root colonization by plant-growth-promoting bacteria could not be useful without the beneficial properties of the bacterium itself. Thus, it is necessary to evaluate the bacterial capacity to form biofilms and establish a successful interaction with the plant roots. We assessed the ability of growth-promoting bacterial strains to form biofilm and display chemotactic behaviour in response to organic acids and (or) root exudates of the model plant Brachypodium distachyon. This assessment was based on the evaluation of single strains of bacteria and a multispecies consortium. The strains coexisted together and formed biofilm under biotic (living root) and abiotic (glass) surfaces. Citric acid stimulated biofilm formation in all individual strains, indicating a strong chemotactic behaviour towards organic acids. Recognizing that the transition from single strains of bacteria to a “multicellular” system would not happen without the presence of adhesion, the alginate and exopolysaccharide (EPS) contents were evaluated. The EPS amounts were comparable in single strains and consortium forms. Alginate production increased 160% in the consortium subjected to drought stress (10% PEG). These findings demonstrated that (i) bacteria–bacteria interaction is the hub of various factors that would not only affect their relation but also could indirectly affect the balanced plant–microbe relation and (ii) root exudates could be very selective in recruiting a highly qualified multispecies consortium.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Sclerosing angiomatoid nodular transformation of spleen masquerading as carcinoma breast metastasis: Importance of splenic biopsy in obviating splenectomy

Metastasis to spleen is rare and usually occurs in the setting of extensive multivisceral metastatic disease. A 60-year-old lady with appropriately managed early breast cancer (breast conservative surgery for Grade-2 infiltrative ductal carcinoma [0.7 cm × 0.5 cm diameter]) in 2006, was detected to have splenic incidentaloma (1.4 cm × 0.8 cm) in November 2012, which was fluoro-deoxy-glucose (FDG) avid on positron emission tomography. Fine needle spiration cytology (FNAC) was normal. More than doubling of lesion size by March 2015 (3.83 cm × 3.03 cm diameter) with persistent FDG positivity lead to Tru-Cut biopsy of spleen, which revealed multiple nodular areas of congestion and hemorrhage, composed of sinusoids (CD31+, CD8+, and CD34−), capillaries (CD31+, CD8−, and CD34+), and small veins (CD31+, CD8−, and CD34−), fibrosis, around these nodular areas along with numerous histiocytes (CD68+) consistent with diagnosis of sclerosing angiomatoid nodular transformation (SANT) of spleen. SANT is a benign, reactive vascular transformation of spleen, notorious to mimic metastasis, the cause of its 18FDG avidity due to its rich content of macrophages and myofibroblasts, usually diagnosed postsplenectomy. This report highlights the importance of splenic biopsy over FNAC is diagnosing splenic incidentalomas, which can help prevent splenectomy, and hence the associated morbidity. This is the first report of SANT in carcinoma breast mimicking metastasis

Efficacy and safety of ultra-rapid lispro insulin in managing type-1 and type-2 diabetes: A systematic review and meta-analysis

Background: Mechanistically, subcutaneous ultra-rapid lispro (URLi) is faster than lispro. Whether this translates into a better post-prandial glucose (PPG) and glycemic control in type-1 diabetes (T1DM) and type-2 diabetes (T2DM) is unclear. Hence, we undertook this meta-analysis. Methods: Databases were searched for randomized controlled trials (RCTs) involving patients with T1DM/T2DM receiving URLi in intervention-arm, and placebo/prandial insulin as control. The primary outcome was a change in PPG. Secondary outcomes were alterations in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), time in range (TIR), and adverse events. Results: Data from six RCTs (3687 patients) were analyzed. Lispro was the control arm in all RCTs. T1DM patients receiving mealtime URLi had lower HbA1c [mean difference (MD) −0.07%; 95% confidence interval (CI): −0.12 to − 0.01; P = 0.02; I2 = 42%] and 1-h PPG [MD − 1.18 mmol/L; 95% CI: −1.91 to − 0.44; P = 0.002; I2 = 100%]. T1DM patients receiving post-meal URLi had comparable HbA1c [MD 0.07%; 95% CI: −0.01 to 0.15; P = 0.07; I2 = 55%] and 1-h PPG [MD 0.22 mmol/L; 95% CI: −0.80 to 1.24; P = 0.67; I2 = 100%). T1DM patients on pumps receiving URLi had comparable TIR [MD 1.70; 95% CI: −0.29 to 3.69; P = 0.09; I2 = 98%], lower time in blood glucose <3 mmol/L with increased infusion-set reactions. T2DM patients receiving mealtime URLi had lower 1-h PPG [MD − 0.66 mmol/L; 95% CI: −0.69 to − 0.63; P < 0.00001; I2 = 0%(LH), 2-h-PPG [MD − 0.96 mmol/L; 95% CI: −1.00 to − 0.92; P < 0.00001; I2 = 0%], higher FPG [MD 0.18 mmol/L; 95% CI: 0.11–0.24; P < 0.00001; I2 = 20%], and higher HbA1c [MD 0.07%; 95% CI: −0.06 to 0.08; P < 0.00001; I2 = 0%]. Conclusion: Pre-meal URLi is better than lispro with regard to PPG control. Post-meal URLi is as good as lispro for PPG control. Post-meal URLi is inferior to pre-meal URLi for PPG control