Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy

Three drugs namely caffeine, paracetamol, and aceclofenac are commonly used for treating various acute and chronic pain related ailments. These 3 drugs have varied solubility profiles, and formulating them into a single tablet did not have the desired dissolution profile for drug absorption. The objective of the present research was to tailor the drug release profile by altering drug solubility. This was achieved by loading the drug into nanosponges. Here, three-dimensional colloidal nanosponges were prepared using β-cyclodextrin with dimethyl carbonate as a cross-linker using the hot-melt compression method. The prepared nanosponges were characterized by FTIR, ¹H NMR spectroscopy, DSC, XRPD studies and SEM. The FTIR and DSC results obtained indicated polymer-drug compatibility. The ¹H NMR spectroscopy results obtained indicated the drug entrapment within nanosponges with the formation of the inclusion complex. XRPD studies showed that the loaded drug had changed crystalline properties altering drug solubility. SEM photographs revealed the porous and spongy texture on the surface of the nanosponge. Box–Behnken experimental design was adopted for the optimization of nanosponge synthesis. Among the synthesized nanosponges containing paracetamol, aceclofenac and caffeine, batch F3–P31, F3–A31 and F3–C31 were considered optimized. Their particle size was 185, 181 and 199 nm with an entrapment efficiency of 81.53, 84.96, and 89.28% respectively. These optimized nanosponges were directly compressed into tablets and were studied for both pre and post-compression properties including in vitro drug release. The prepared tablet showed desired drug dissolution properties compared to the pure drug. The above outcomes indicated the applicability of nanosponges in modulating the drug release with varied solubility for combination therapy.

Polymeric nanosponges as potential carriers for successful combination therapy of poorly soluble drugs (paracetamol, aceclofenac, caffeine).     

Biological activation of bone grafts using injectable platelet-rich fibrin

Platelet-rich fibrin (PRF) is gaining acceptance as a bioactive surgical additive in regenerative dentistry. However, PRF has only been available in gel or membrane form and is not suitable for injection. Recently, however, a liquid, injectable PRF has been introduced. This paper introduces the concept of injectable PRF and discusses its applications for biologic activation of bone grafts.     

Association of pulse pressure,pulse pressure index,and ambulatory arterial stiffness index with kidney function in a cross‐sectional pediatric chronic kidney disease cohort from the CKiD study

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end‐stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1‐16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non‐immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non‐immunological group. There were no significant differences with iohexol‐based glomerular filtration rate (iGFR), LVMI, PPi, or high‐sensitivity C‐reactive protein (hs‐CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non‐immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.     

The feasibility of using mobile phone technology for sexual behaviour research in a population vulnerable to HIV: a prospective survey with female sex workers in South India

Sexual behaviour studies are often challenged by sampling, participation and measurement biases, and may be unacceptable to participants. We invited 293 randomly selected female sex workers (FSWs) in Bangalore, India, to participate in a telephone survey, with condom breakage as the main outcome. Free cell phones were supplied and trained interviewers telephoned FSWs daily to ask about all sex acts the previous day. Later, we undertook focus groups to discuss the methodology with the participants. We evaluated technical and operational feasibility; data reliability and measurement error; emotional and fatigue effects; interviewer bias; survey reactivity effects; and user acceptability. Response rates were high, with 84% of invited participants complying fully with the protocol. The study ran smoothly, with little evidence of biases. The methodology was highly acceptable; the respondents enjoyed using a new telephone and being interviewed at times convenient to them. Other reasons for the success of the method were that the study was sanctioned and supported by the sex worker collective, and the interviewers were well trained and developed a strong rapport with the participants. The success of this methodology, and the wealth of data produced, indicates that it can be an important tool for conducting sexual behaviour research in low literacy, high sex volume populations.     

Clinical findings associated with bladder trabeculations in women

Introduction and hypothesis

This study evaluated whether bladder trabeculations are associated with advanced prolapse, urinary urgency, or detrusor overactivity among women undergoing office cystoscopy. It is well established that bladder trabeculations are associated with bladder outlet obstruction (BOO) in men; however, the clinical significance of trabeculations in women is unclear. Whereas an analogous relationship has been proposed between prostatic obstruction in men and advanced pelvic organ prolapse (POP) in women, little data in the medical literature supports this theory.

Methods

A retrospective cohort study was conducted using Current Procedural Terminology (CPT) codes (52000, 52204) to identify all women who underwent office cystoscopy at our urogynecology center between January 2008 and May 2011. The 551 women identified were grouped by the presence or absence of bladder trabeculations. Multivariable logistic regression was used to estimate the association between trabeculations and the primary aim, increasing stage of prolapse, and the secondary aims: bladder outlet obstruction, detrusor overactivity, or urge urinary incontinence (UUI).

Results

Of the 551 women meeting inclusion criteria, 86 had trabeculations. Controlling for age, the odds of bladder trabeculations were eightfold greater for women with stage IV POP when compared with women with stage 0 prolapse [odds ratio (OR) 8.2, 95 % confidence interval (CI) 1.6–43.1]. The odds of bladder trabeculations were twofold greater for women with detrusor overactivity (OR 2.3, 95 % CI 1.3–4.0) found on urodynamic study and also as reflected subjectively by answers to Pelvic Floor Distress Inventory (PFDI) item number 16 (OR 4.2, 95 % CI 1.3–14.5).

Conclusion

In this study, bladder trabeculations were associated with stage IV prolapse in the anterior compartment as well as with detrusor overactivity and UUI.     

A retrospective analysis of early experience with modified complete primary repair of exstrophy bladder (CPRE) in neonates and children

Objective:

To study the problems faced during the surgery and follow-up of modified complete primary repair of exstrophy (CPRE) technique. Initial experience with CPRE and its short- and long-term outcomes with respect to continence status and psychosocial impact are reported.

Materials and Methods:

A retrospective review of the hospital case records from March 2008 to September 2012 was performed. Data of patients with bladder exstrophy managed by a single paediatric surgeon using modified CPRE technique were analysed. Quality of life and psychosocial impact of the surgery were assessed using Pediatric Quality of Life Inventory (PedsQL 4.0) and compared with those of typical peers.

Results:

Eight children (age 4 days-12 years) underwent CPRE using modified Mitchell''s technique. Two patients (25%) experienced early postoperative complications, with infection and fistula developing in one each. All the patients were doing well on follow-up, with variable continence rates and good cosmesis. Mean duration of follow-up was 18.5 months (range 6 months-4 years). Five out of seven (71%) children were continent or partially continent. One case was lost to follow-up. PedsQL scores were comparable with those of age-matched peers in all domains except the social functioning domain in 8-12 years age group (83.53 ± 9.70 vs. 77.86 ± 10.22, P < 0.05).

Conclusion:

Our preliminary results with modified CPRE in neonates and children have been encouraging. No major complications were observed. Continence rate was satisfactory and cosmetic results were good. Though the technique is being practiced at several Indian centres, there is a paucity of comprehensive Indian data on CPRE.KEY WORDS: Bladder exstrophy, complete primary repair, urinary continence     

A rare presentation of hepatic and splenic cystic malignant fibrous histiocytoma: A case report and literature review

INTRODUCTIONMalignant fibrous histiocytoma is one of the most common soft tissue sarcomas in late adult life. But primary visceral malignant fibrous histiocytoma is a very rare entity. In peripheries, it is known to have an aggressive behavior but its biological pattern when involving liver and spleen is not well understood due to the rarity of its occurrence.PRESENTATION OF CASEA case of malignant fibrous histiocytoma of the liver and spleen as multiple cystic lesions in a 30 years old man is reported. The patient presented with hepatosplenomegaly resulting in central abdominal distention. Pre-operative investigations pointed toward the diagnosis of malignant cystic disease. The tumor presented as multiple hepatic cysts with massive hepatomegaly and splenomegaly. These cysts contained hemorrhagic fluid. Biopsy revealed highly cellular pleomorphic spindle cells fascicles arranged in storiform pattern at places with frequent mitoses. Immunohistochemistry revealed viamentin positivity. The tumor is compared with previous case reports.DISCUSSIONMalignant fibrous histiocytoma of liver and spleen has been mentioned in the literature as isolated case reports and most of these present as solid lesions but presentation as multiple cysts is also a possibility as was seen in this patient. It can be confirmed only on histo-pathology supported by immunohistochemistry. The disease carries guarded prognosis due to its rapid progression and diagnostic dilemma pre-operatively.CONCLUSIONThis rare malignancy affecting the viscera can be diagnosed only with high index of suspicion and awareness regarding its presentation can help surgeons deal with it.