La langosta espinosa Panulirus homarus, distribuida a lo largo de las costas sudeste y sudoeste de la India, es una especie de importancia comercial con gran potencial para la mari-cultura. A pesar de su importancia, las características estructurales y ultraestructurales de las gónadas masculinas de esta especie han sido poco estudiadas. Debido a esto, el objetivo de este estudio fue describir el aparato reproductor masculino de dicha especie, utilizando técnicas convencionales de microscopía histológica y electrónica. Se procesaron 94 ejemplares de P. homarus de vizhinjam (costa suroeste de la India) (70 individuos para histología y 24 para ultraestructura), cuyos caparazones variaron de 37 mm a 92 mm de longitud. El sistema reproductor masculino de esta especie consistió en un par de testículos y un conducto deferente situados en la región céfalo-torácica. Macroscópicamente, el aparato reproductor se observó en langostas con una longitud de caparazón >35mm. En testículos inmaduros, la espermatogonia midió 6.9-13.8μm de diámetro y se encontró presente en los testículos maduros primarios (5.4-5.9μm), espermatocitos secundarios (2.8 a 3 μm) y espermátidas (2.2-2.4μm). Cada conducto deferente consistió de porciones proximales y distales. La formación de la masa espermatofórica comienza en los conductos deferentes proximales. En el conducto deferente distal espermatofórico, la masa que contiene los espermatozoides está dispuesta en paquetes hacia la periferia, en una matriz gelatinosa producida por el tiflosol. Ultraestructuralmente, las espermatogonias presentan una lámina, núcleo y mitocondrias, los espermatocitos primarios tienen núcleo, cromatina densa y citoplasma vacuolado, mientras que las espermátidas tienen mitocondrias, retículo endoplasmático y centríolos. En las espermátidas, el retículo endoplásmico y la envoltura nuclear forman el acrosoma. Los brazos radiales con microtúbulos se forman en asociación con el retículo endoplásmico denso, cerca del núcleo. El esperma presenta una estructura esférica con el núcleo, la región laminar, las espinas y el acrosoma. Este documento constituye el primer informe exhaustivo de la estructura de los gametos masculinos y espermatogénesis en P. homarus de la India.

The spiny lobster Panulirus homarus, distributed along the Southeast and Southwest coasts of India, is an important commercial species having mariculture potential. Despite its importance, the structural and ultrastructure features of male gonads from this species have received scarce attention. Hence this study was aimed to describe the male reproductive tract of the species, using standard histological and electron microscopy techniques. Gonads from 94 specimens of P. homarus ranging in carapace length 37mm-92mm from vizhinjam (Southwest coast of India.) were obtained and processed for the study (Histology-70 numbers & ultrastructure-24 numbers). The male reproductive system consists of paired testis and vas deferens located in the cephalothoracic region. Macroscopically, the reproductive tract was observed in lobsters >35mm carapace length. In immature testis, spermatogonia were seen which measured 6.9-13.8µm in diameter and in the mature testis primary (5.4-5.9µm) and secondary spermatocytes (2.8-3µm) and spermatids (2.2-2.4µm) were present. Each vas deferens consists of proximal and distal portions. The spermatophoric mass begins formation in the proximal vas deferens. In the distal vas deferens the spermatophoric mass containing the spermatozoa are arranged in packets towards the periphery by the gelatinous matrix produced by the typhlosole. Ultrastructurally, the spermatogonia have lamina, nucleus and mitochondria like bodies, the primary spermatocytes have nucleus, dense chromatin and vacuolated cytoplasm and the spermatids have mitochondria, endoplasmic reticulum and centrioles. The endoplasmic reticulum and the nuclear envelope in the spermatids form the acrosome. The radial arms with microtubules are formed in association with the dense endoplasmic reticulum, near the nucleus. The sperm has a spherical structure with the nucleus, lamellar region, spikes and acrosome. This is the first comprehensive report of the structure of the male gametes and spermatogenesis in P. homarus from Indian waters.Rev. Biol. Trop. 62 (2): 533-541. Epub 2014 June 01.

PurposeThe objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT) transdermal gel and to evaluate its pharmacokinetic properties.Materials and MethodsTaguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats.ResultsTransdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24) was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2). Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5%) and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1) was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides.ConclusionResults indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder.

Glicoproteína-p (P-gp), uma glicoproteína de transmembrana permeável, é um membro da superfamília (ABC) de cassete de gene de ligação de ATP que funciona especificamente como um carreador mediado pelo transportador de efluxo ativo primário. É amplamente distribuído por todo o corpo e apresenta uma gama diversificada de substratos. Diversos agentes terapêuticos vitais são substratos para P-gp e sua biodisponibilidade é reduzida ou a resistência é induzida devido ao efluxo de proteínas. Portanto, os inibidores da P-gp foram explorados para a superação da resistência a múltiplas drogas e problemas de biodisponibilidade deficiente dos substratos terapêuticos da P-gp. A sensibilidade das moléculas da droga à P-gp e vice-versa, pode ser estabelecida por vários modelos experimentais in silico, in vitro e in vivo. Desde a descoberta da P-gp, diversas pesquisas identificaram várias estruturas químicas como inibidores da P-gp. O objetivo deste presente estudo foi o de enfatizar a descoberta e desenvolvimento de inibidores mais novos, inertes, atóxicos e mais eficazes, visando especificamente os da P-gp, como aqueles entre os extratos vegetais, excipientes e formulações farmacêuticas, e outras moléculas racionais de droga. As aplicações do conhecimento de biologia celular e molecular, bancos de dados estruturais in silico, estudos de modelagem molecular e análises da relação quantitativa estrutura-atividade (QSAR) no desenvolvimento de novos inibidores racionais da P-gp também foram mencionados.

P-glycoprotein (P-gp), a transmembrane permeability glycoprotein, is a member of ATP binding cassette (ABC) super family that functions specifically as a carrier mediated primary active efflux transporter. It is widely distributed throughout the body and has a diverse range of substrates. Several vital therapeutic agents are substrates to P-gp and their bioavailability is lowered or a resistance is induced because of the protein efflux. Hence P-gp inhibitors were explored for overcoming multidrug resistance and poor bioavailability problems of the therapeutic P-gp substrates. The sensitivity of drug moieties to P-gp and vice versa can be established by various experimental models in silico, in vitro and in vivo. Ever since the discovery of P-gp, the research plethora identified several chemical structures as P-gp inhibitors. The aim of this review was to emphasize on the discovery and development of newer, inert, non-toxic, and more efficient, specifically targeting P-gp inhibitors, like those among the natural herb extracts, pharmaceutical excipients and formulations, and other rational drug moieties. The applications of cellular and molecular biology knowledge, in silico designed structural databases, molecular modeling studies and quantitative structure-activity relationship (QSAR) analyses in the development of novel rational P-gp inhibitors have also been mentioned.