Formulation Development and Evaluation of Innovative Two-Polymer (SR-2P) Bioadhesive Vaginal Gel

The main objective of this investigation was to study the feasibility of developing a vaginal bioadhesive microbicide using a SRI’s proprietary two-polymer gel platform (SR-2P). Several formulations were prepared with different combinations of temperature-sensitive polymer (Pluronic® F-127) and mucoadhesive polymer (Noveon® AA-1), producing gels of different characteristics. Prototype polymeric gels were evaluated for pH, osmolality, buffering capacity, and viscosity under simulated vaginal semen dilutions, and bioadhesivity using ex vivo mini pig vaginal tissues and texture analyzer. The pH of the polymeric gel formulations ranged from 5.1 to 6.4; the osmolality varied from 13 to 173 mOsm. Absolute viscosity ranged from 513 to 3,780 cPs, and was significantly reduced (1.5- to 3-fold) upon incubation with simulated vaginal and semen fluid mixture. Among the tested gels (indicated in the middle row as a molar ratio of a mixture of Noveon vs. Pluronic), only SR-2P retained gel structure upon dilution with simulated fluids and mild simulated coital stress. The pH of the SR-2P gel was maintained at about 4.6 in simulated vaginal fluid and also showed high peak force of adhesion in mini pig vaginal tissue. Furthermore, SR-2P gel caused no or only minimal irritation in a mouse vaginal irritation model. The results of this preliminary study demonstrated the potential application of SR-2P gel as a vaginal microbicide vehicle for delivery of anti-HIV agents.

Bladder Leiomyoma Presenting With LUTS and Coexisting Bladder and Uterine Leiomyomata: A Review of Two Cases

Mesenchymal tumors of the urinary bladder are a rare occurrence, the most common among them being leiomyoma of the bladder. These tumors commonly present with irritative urinary symptoms progressing gradually to obstructive symptoms as the size increases. We report on two patients who presented with lower urinary tract symptoms (LUTS). One of the patients also had concomitant bladder and uterine leiomyomata, which is the first such case to be reported in the literature. It is essential to differentiate leiomyoma from other common causes of LUTS. Cold cup biopsy has a significant false-negative rate and, in such cases, a wide local excision provides an optimal cure with excellent results.Key words: Bladder leiomyoma, Uterine fibroid, Lower urinary tract symptomsBenign tumors of the urinary bladder are rare and can present with a wide spectrum of complaints ranging from irritative to obstructive urinary symptoms.¹ Here we report on two patients who presented with lower urinary tract symptoms (LUTS), one of whom also had concomitant multiple uterine fibroids. To our knowledge, this is the first case to be reported in the literature.     

Effect of protonation and hydrogen bonding on 2, 4, 6-substituted pyrimidine and its salt complex-experimental and theoretical evidence

The short-range properties of alkylpiperazine ionic liquids paired with propionate and lactate anions were analyzed and their affinity for CO₂ molecules studied using density functional theory. Anion–cation interactions led to the development of strong intermolecular hydrogen bonding through the cation amine position, as confirmed through variations in structural and vibrational properties upon pair formation. Topological analysis via the atoms-in-molecules approach revealed the development of intense bond and ring critical points in the intermolecular regions, which is in agreement with charge transfer from lone pairs in anion oxygen atoms of carboxylate groups through antibonding orbitals in cation amine groups. Such anion–cation interactions are weakly dependent on cation alkyl chain length but are remarkably affected by the presence of an anion hydroxyl group. Interactions with CO₂ molecules are stronger for anions than for cations, especially for propionate anions, and are also affected strongly by the anion hydroxyl group.     

HDAC3-dependent reversible lysine acetylation of cardiac myosin heavy chain isoforms modulates their enzymatic and motor activity

Reversible lysine acetylation is a widespread post-translational modification controlling the activity of proteins in different subcellular compartments. We previously demonstrated that a class II histone deacetylase (HDAC), HDAC4, and a histone acetyltransferase, PCAF, associate with cardiac sarcomeres, and a class I and II HDAC inhibitor, trichostatin A, enhances contractile activity of myofilaments. In this study, we show that a class I HDAC, HDAC3, is also present at cardiac sarcomeres. By immunohistochemical and electron microscopic analyses, we found that HDAC3 was localized to the A band of sarcomeres and was capable of deacetylating myosin heavy chain (MHC) isoforms. The motor domains of both cardiac α- and β-MHC isoforms were found to be reversibly acetylated. Biomechanical studies revealed that lysine acetylation significantly decreased the K(m) for the actin-activated ATPase activity of both α- and β-MHC isoforms. By an in vitro motility assay, we found that lysine acetylation increased the actin sliding velocity of α-myosin by 20% and β-myosin by 36%, compared to their respective non-acetylated isoforms. Moreover, myosin acetylation was found to be sensitive to cardiac stress. During induction of hypertrophy, myosin isoform acetylation increased progressively with duration of stress stimuli, independent of isoform shift, suggesting that lysine acetylation of myosin could be an early response of myofilaments to increase contractile performance of the heart. These studies provide the first evidence for localization of HDAC3 at myofilaments and uncover a novel mechanism modulating the motor activity of cardiac MHC isoforms.     

Colorimetric detection of melamine in milk by citrate-stabilized gold nanoparticles

Here, we report a simple and sensitive colorimetric method for detection of melamine in milk using gold nanoparticles (AuNPs). AuNPs of 21-nm size were synthesized by the citrate reduction method. The method is based on the principle that the melamine causes the aggregation of AuNPs and, hence, the wine red color of AuNPs changes to blue or purple. This change in color can be visualized with the naked eye or an ultraviolet–visible (UV–Vis) spectrometer. Under optimized conditions, AuNPs are highly specific for melamine and can detect melamine down to a concentration of 0.05 mg L⁻¹.     

Genetic diversity analysis in disjunct populations of Rhododendron arboreum from the temperate and tropical forests of Indian subcontinent corroborate Satpura hypothesis of species migration

Rhododendron arboreum of the family Ericaceae represents one of the ancient relict tree species of the genus showing extreme disjunction in the Indian subcontinent. It is represented by two sub-species viz., ssp. arboreum Smith in the forests of north-eastern India (temperate) and spp. nilagiricum (Zenker) Tagg distributed in the southern Western Ghats (tropical) of India with apparently no distribution in the intervening plains. 35 Samples corresponding to different locations in the tropical montane forests of Nilgiris and temperate forests of northeast India were analyzed for distribution of genetic variation using 25 random primers. Relatively high genetic diversity was measured in the temperate populations (Ht = 0.21; Nm = 1.13) than tropical Rhododendrons. The hierarchical analysis of molecular variance showed that among the total variance, 25% is residing within populations while 63% of variance is among regions apparently revealing that disjunct distribution has structured genetic differentiation pattern in this species. Grouping of samples was in conformity with their spatial distribution, which was confirmed by UPGMA cluster analysis and PCA scatter plot. The taxon with its unique distribution pattern and wide cross compatibility between sub-species is however threatened by low genetic variation and gene flow that catalyses it’s shifting towards genetic drift and hence long-term conservation strategies need to be formulated particularly for the tropical Rhododendron sub-species. Among the various hypotheses and theory proposed to explain the Malayan affinity in the flora and fauna of Western Ghats, Satpura hypothesis based on dispersal model of distribution largely explains the discontinues distribution of R. arboreum.     

New and unusual forms of calcium oxalate raphide crystals in the plant kingdom

Calcium oxalate crystals in higher plants occur in five major forms namely raphides, styloids, prisms, druses and crystal sand. The form, shape and occurrence of calcium oxalate crystals in plants are species- and tissue-specific, hence the presence or absence of a particular type of crystal can be used as a taxonomic character. So far, four different types of needle-like raphide crystals have been reported in plants. The present work describes two new and unusual forms of raphide crystals from the tubers of Dioscorea polystachya—six-sided needles with pointed ends (Type V) and four-sided needles with beveled ends (Type VI). Both of these new types of needles are distinct from the other four types by each having a surrounding membrane that envelopes a bundle of 10–20 closely packed thin crystalline sheets. The previously known four types of needles have solid or homogenous crystalline material, surrounded by a membrane or lamellate sheath called a crystal chamber. Only the Type VI crystals have beveled ends and the needles of the other five types have pointed ends.     

The State-Led Large Scale Public Private Partnership ‘Chiranjeevi Program’ to Increase Access to Institutional Delivery among Poor Women in Gujarat,India: How Has It Done? What Can We Learn?

Background

Many low-middle income countries have focused on improving access to and quality of obstetric care, as part of promoting a facility based intra-partum care strategy to reduce maternal mortality. The state of Gujarat in India, implements a facility based intra-partum care program through its large for-profit private obstetric sector, under a state-led public-private-partnership, the Chiranjeevi Yojana (CY), under which the state pays accredited private obstetricians to perform deliveries for poor/tribal women. We examine CY performance, its contribution to overall trends in institutional deliveries in Gujarat over the last decade and its effect on private and public sector deliveries there.

Methods

District level institutional delivery data (public, private, CY), national surveys, poverty estimates, census data were used. Institutional delivery trends in Gujarat 2000–2010 are presented; including contributions of different sectors and CY. Piece-wise regression was used to study the influence of the CY program on public and private sector institutional delivery.

Results

Institutional delivery rose from 40.7% (2001) to 89.3% (2010), driven by sharp increases in private sector deliveries. Public sector and CY contributed 25–29% and 13–16% respectively of all deliveries each year. In 2007, 860 of 2000 private obstetricians participated in CY. Since 2007, >600,000 CY deliveries occurred i.e. one-third of births in the target population. Caesareans under CY were 6%, higher than the 2% reported among poor women by the DLHS survey just before CY. CY did not influence the already rising proportion of private sector deliveries in Gujarat.

Conclusion

This paper reports a state-led, fully state-funded, large-scale public-private partnership to improve poor women’s access to institutional delivery - there have been >600,000 beneficiaries. While caesarean proportions are higher under CY than before, it is uncertain if all beneficiaries who require sections receive these. Other issues to explore include quality of care, provider attrition and the relatively low coverage.