A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine

Background: There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine.

Study design: Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices.

Results: A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm.

Conclusions: The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. © 2013 Elsevier Inc. All rights reserved.

The automatic layout model in the sequencing of construction activities of multi-objective diaphragm wall unit by using self-learning neural network

Foundation construction process has been an important key point in a successful construction engineering. The frequency of using diaphragm wall construction method among many deep excavation construction methods in Taiwan is the highest in the world. The traditional view of managing diaphragm wall unit in the sequencing of construction activities is to establish each phase of the sequencing of construction activities by heuristics. However, it conflicts final phase of engineering construction with unit construction and effects planning construction time. In order to avoid this kind of situation, we use management of science in the study of diaphragm wall unit construction to formulate multi-objective combinational optimization problem. Because the characteristic (belong to NP-Complete problem) of problem mathematic model is multi-objective and combining explosive, it is advised that using the 2-type Self-Learning Neural Network (SLNN) to solve the N=12, 24, 36 of diaphragm wall unit in the sequencing of construction activities program problem. In order to compare the liability of the results, this study will use random researching method in comparison with the SLNN. It is found that the testing result of SLNN is superior to random researching method in whether solution-quality or Solving-efficiency.

Anatomical study of the diaphragm of the opossum (Didelphis albiventris)

The anatomical characteristics of the South American opossum diaphragm were described. Five male and seven female adult opossums, weighing between 700 and 1110 g, were used. Animals were killed by ether inhalation saturation. The abdominal and thoracic walls were dissected and opened, the viscerae were removed and the diaphragm anatomy was described and photographed in situ . After diaphragm removal, some dimensional data were taken and tabled. Primary branches of the phrenic nerves were dissected under a surgical microscope. The secondary branches were studied and described by transillumination after clarification in acetic acid. The opossum diaphragm is domed and has a mean area of 54.33 +/- 3.8 cm(2) . Well-identified costal, sternal and lumbar parts form the peripheral muscular region. The central tendinous region presents with a V-like form. Three folioles comprise the phrenic centre and present different dimensions. The caudal vena cava passes through its foramen between the ventral and right dorsal folioles. Both right and left phrenic nerves present one ventral branch and one dorsolateral trunk in 50.0% and 66.67% of the cases, respectively.

Morphometric and morphological analysis of neuromuscular junction alterations in the denervated rat diaphragm

The morphological and structural alterations that occur in the neuromuscular junctions of the denervated rat diaphragm were studied. Fifteen adult male albino rats (Rattus norvegicus) aged about 60 days and with a mean weight of 200 g were used. Chronically denervated diaphragms were obtained and the animals were sacrificed after 4, 8 and 12 weeks of denervation. The left antimere of the diaphragm was denervated by section of the phrenic nerve and the right antimere was used as control. Each antimere was divided into three fragments: one was used for histochemical (nonspecific esterase) and morphometric study of neuromuscular junctions, and the other two were used for transmission and scanning electron microscopy (SEM) analysis. Histochemical analysis of the diaphragm neuromuscular junctions after denervation showed only small changes in junction morphology. However, these junctions became smaller and elongated and presented less visible contours with increasing time of denervation. Ultrastructural analysis of neuromuscular junctions after 12 weeks showed more or less organized junctional folds on the muscle fiber surface. The junctional cytoplasm exhibited important alterations such as mitochondrial degeneration and the presence of numerous filaments. SEM revealed the presence of deep primary synaptic grooves with peripheral excavations which housed the nerve terminal boutons and exhibited internally the secondary synaptic clefts present among the junctional folds of the sarcolemma. This study showed that some of the morphological changes demonstrated in other denervated striated skeletal muscles are not repeated at the same intensity or in the same temporal pattern in the rat diaphragm.

Morphologic alterations resulting from denervation of the diaphragm in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Down-regulation of MyoD gene expression in rat diaphragm muscle with heart failure

Diaphragm myopathy has been described in patients with heart failure (HF), with alterations in myosin heavy chains (MHC) expression. The pathways that regulate MHC expression during HF have not been described, and myogenic regulatory factors (MRFs) may be involved. The purpose of this investigation was to determine MRF mRNA expression levels in the diaphragm. Diaphragm muscle from both HF and control Wistar rats was studied when overt HF had developed, 22 days after monocrotaline administration. MyoD, myogenin and MRF4 gene expression were determined by RT-PCR and MHC isoforms by polyacrylamide gel electrophoresis. Heart failure animals presented decreased MHC IIa/IIx protein isoform and MyoD gene expression, without altering MHC I, IIb, myogenin and MRF4. Our results show that in HF, MyoD is selectively down-regulated, which might be associated with alterations in MHC IIa/IIx content. These changes are likely to contribute to the diaphragm myopathy caused by HF.

Guanidine Affects Differentially the Twitch Response of Diaphragm, Extensor Digitorum Longus and Soleus Nerve-Muscle Preparations of Mice

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The number of podocyte and slit diaphragm is decreased in experimental diabetic nephropathy

Purpose: To determine the number of podocyte, slit diaphragms, slit diaphragm extensions and GBM thickness in diabetic nephropathy. Methods: Sixty Rattus Wistarof both sexes weighing 200-300g were divided in two experimental groups: normal group 10 animals, and alloxan diabetic rats - 50 animals. Alloxan was administered in a single IV dose of 42mg/kg body weight. Body weight, water and food intake, diuresis, and blood and urine glucose were determined in both groups before alloxan injection and two weeks, six and twelve months after alloxan injection. Proteinuria was measured at 12 months in both groups. After 12 months animals were sacrificed, and the right kidney processed for electron microscopy. Results: Clear clinical and laboratory signs of severe diabetes were seen, in all alloxan-diabetic rats at all follow-up times. Glomerular basement membrane (GBM) thickening, podocyte number, and slit diaphragm number and extension were determined. GBM of all diabetic rats was significantly thicker (median=0.29μm; semi-interquartile range=0.065μm) than in the normal rats (0.23μm; 0.035μm). Diabetic rat podocyte number (8; 1), slit diaphragm number (4; 1), and slit diaphragm extension (0.021μm; 0.00435μm) were significantly lower than in normal rats (11; 1) and (7; 1.5), and (0.031μm; 0.0058μm). Diabetic rat proteinuria (0.060mg/24h; 0.037mg/24h) was higher than in normal rats (0.00185mg/24h; 0.00055mg/24h). Conclusion: Experimental diabetes is associated with significant (p<0.05) changes in podocyte foot process, slit number, slit diaphragm extension, and GBM thickness.

Ultrastructural Study of the Denervated Diaphragm in Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)