bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endocytosis in spermatids during spermiogenesis of the mouse
Authors: Segretain Dominique 
Published: February 2012

In the course of spermiogenesis in the mouse, spermatid cytoplasm contains numerous membrane pits, vesicles and membranous tubules which are frequently anastomosed. Pale and dense multivesicular bodies (MVB) and secondary lysosome‐like structures are also present in the cytoplasm. In order to study the pathway of non‐specific adsorptive endocytosis in spermatids, cationic ferritin (CF) was directly microinjected into the lumen of seminiferous tubules, and added to germinal cell culture. Tissue and cultures were fixed at various time intervals after injection.Two‐5 hr after microinjection of tracer, CF was found simultaneously in vesicles, tubules, MVB and in lysosome‐like bodies present in spermatids at all steps of spermiogenesis. Various membranous components of the Golgi medulla, and the innermost transsaccule of the Golgi cortex were labelled simultaneously. In primary cultures of spermatids, the vesicles contained the marker 5 min after its deposition; 10 min after deposition, CF was evident in tubules; at 30 min, CF was present in pale MVB; at 1 hr, the dense MVB and lysosome‐like bodies were labelled. Finally, at 2 hr 30 min, vesicles and tubules of the Golgi medulla contained CF grains.Apparently spermatids are very active cells in the process of adsorptive endocytosis throughout spermiogenesis. Endocytosis in spermatids is probably one of the mechanisms involved in the uptake of material used to build up spermatozoa components. The strong labelling of the Golgi region probably point to its role in recycling endocytosed membranes.
In vitro effects of colchicine and nocodazole on ciliogenesis in quail oviduct
Authors: Boisvieux‐Ulrich Emmanuelle , Lainé Marie‐Christine , Sandoz Daniel 
Published: February 2012

Summary— Oviduct implants from quails which were primarily stimulated in vivo by estrogen so as to induce ciliogenesis in some epithelial cells were cultured in vitro in the presence or absence of colchicine or nocodazolc. After 24 or 48 hr of culture, implants were examined by transmission and scanning electron microscopy to determine drug‐induced alterations in ciliogenesis.After 24 hr of 10−5 M colchicine treatment, the formation of basal bodies was totally inhibited, though the precursor material of generative complexes was unchanged. The inhibitory effect was not reversed when colchicine was removed in a 24 hr recovery culture. Treatment with 10−6 M nocodazole for 24 hr, partially inhibited the assembly of basal bodies, which exhibited altered morphology. The assembly of basal bodies was restored during the 24 hr recovery period, after removal of nocodazole.Colchicine and nocodazole did not prevent polarized migration towards the apical surface of basal bodies formed prior to drug treatment. They anchored to the plasma membrane, but the formation of cilia was strongly disturbed in the presence of the drug. Numerous cells possessed anchored basal bodies which failed to induce the formation of cilia.The elongation of cilia was inhibited, as seen by their abnormal capping structure. In the enlarged tip, microtubules diverged. In contrast, these very short cilia possessed a mature ciliary necklace which was constructed during drug treatment. Differentiation of this membrane ciliary structure appeared to be unrelated to axoneme growth.
Organization of actin microfilaments in the apical border of oviduct ciliated cells
Authors: Chailley Bernadette , Nicolas Gisèle , Lainé Marie‐Christine 
Published: February 2012

Summary— Actin microfilaments were localized in quail oviduct ciliated cells using decoration with myosin subfragment S1 and immunogold labeling. These polarized epithelial cells show a well developed cytoskeleton due to the prosence of numerous cilia and microvilli at their apical pole. Most S1‐decorated microfilaments extend from the microvilli downward towards the upper part of the ciliary striated rootlets with which they are connected. From the microvillous roots, a few microfilaments connect the proximal part of the basal body or the basal foot associated with the basal body. Microfilament polarity is shown by S1 arrowheads pointing away from the microvillous tip to the cell body. Furthermore, short microfilaments are attached to the plasma membrane at the anchoring sites of basal bodies and run along the basal body. The polarity of these short microfilaments is directed from the basal body anchoring fibers downward to the cytoplasm. At the cell periphery, microfilaments from microvillous roots and ciliary apparatus are connected with those of the circumferential actin belt which is associated with the apical zonula adhaerens.Together with the other cytoskeletal elements, the microfilaments increase ciliary anchorage and could be involved in the coordination of ciliary beating. Moreover, microvilli surrounding the cilia probably modify ciliary beating by offering resistance to cilium bending. The presence of microvilli could explain the fact that mainly the upper part of the cilia appanars to be involved in the axonemal bending in metazoan ciliated cells.
In situ response to vinka alkaloids by microtubules in cultured post‐implanted mouse embryos
Authors: Meininger Vincent , Binet Stéphane , Chaineau Eric , Fellous Arlette 
Published: February 2012

Summary— The response of microtubules to treatment with vinca alkaloids was investigated in vivo and in situ in the embryonic nervous system of mice. For this purpose we used rotatory cultures of post‐implanted embryos in a serum medium containing the alkaloid combined with immunofluorescence using a tubulin‐specific polyclonal antibody on high molecular weight polyethylene glycol embedded semithin sections.In mitotic cells, kinetochore microtubules were seen to be more resistant to the action of vinca alkaloids than interpolar microtubules. Increasing drug concentrations induced an increasing rate of mitosis together with an increasing rate of disassembly of the cytoplasmic microtubule complex, suggesting a probable relation between these events.In bipolar neuroepithelial cells at interphase, a small pool of microtubules was resistant to the vinca alkaloids. These microtubules were located near the centriolar apparatus associated with the primary cilium; they were short, curly and bent. Disruption of the cytoplasmic microtubule complex did not alter the shape of the bipolar neuroepithelial cells.In the axonal profiles, a drug‐stable pool of microtubules were not disrupted by the alkaloids and were also short. They seem to act as microtubule organizing centres.These observations suggest vinca alkaloids seem to act in vivo much more by inducing, at a given concentration, the disruption of a particular group of microtubules without altering the others. The fact that these drugs affect the number, but not the length, of the microtubules raises the hypothesis that these drugs act on microtubules by a mechanism similar to that described as “dynamic instability”.
An evaluation of the potential of linear and nonlinear skin permeation models for the prediction of experimentally measured percutaneous drug absorption
Authors: Brown Marc B , Lau Chi-Hian , Lim Sian T , Sun Yi , Davey Neail , Moss Gary P , Yoo Seon-Hie , De Muynck Christian 
Published: February 2012

Abstract

Objectives
The developments in combinatorial chemistry have led to a rapid increase in drug design and discovery and, ultimately, the production of many potential molecules that require evaluation. Hence, there has been much interest in the use of mathematical models to predict dermal absorption. Therefore, the aim of this study was to test the performance of both linear and nonlinear models to predict the skin permeation of a series of 11 compounds.

Methods
The modelling in this study was carried out by the application of both quantitative structure permeability relationships and Gaussian process-based machine learning methods to predict the flux and permeability coefficient of the 11 compounds. The actual permeation of these compounds across human skin was measured using Franz cells and a standard protocol with high performance liquid chromatography analysis. Statistical comparison between the predicted and experimentally-derived values was performed using mean squared error and the Pearson sample correlation coefficient.

Key findings
The findings of this study would suggest that the models failed to accurately predict permeation and in some cases were not within two- or three-orders of magnitude of the experimentally-derived values. However, with this set of compounds the models were able to effectively rank the permeants.

Conclusions
Although not suitable for accurately predicting permeation the models may be suitable for determining a rank order of permeation, which may help to select candidate molecules for in-vitro screening. However, it is important to note that such predictions need to take into account actual relative drug candidate potencies.
Clove and eugenol in noncytotoxic concentrations exert immunomodulatory/anti-inflammatory action on cytokine production by murine macrophages
Authors: Bachiega Tatiana Fernanda , de Sousa João Paulo Barreto , Bastos Jairo Kenupp , Sforcin José Maurício 
Published: February 2012

Abstract

Objectives
The extract and essential oil of clove (Syzygium aromaticum) are widely used because of their medicinal properties. Eugenol is the most important component of clove, showing several biological properties. Herein we have analysed the immunomodulatory/anti-inflammatory effect of clove and eugenol on cytokine production (interleukin (IL)-1β, IL-6 and IL-10) in vitro.

Methods
Macrophages were incubated with clove or eugenol (5, 10, 25, 50 or 100 µg/well) for 24 h. Concentrations that inhibited the production of cytokines were used before or after incubation with lipopolysaccharide (LPS), to verify a preventive or therapeutic effect. Culture supernatants were harvested for measurement of cytokines by enzyme-linked immunosorbent assay.

Key findings
Clove (100 µg/well) inhibited IL-1β, IL-6 and IL-10 production and exerted an efficient action either before or after LPS challenge for all cytokines. Eugenol did not affect IL-1β production but inhibited IL-6 and IL-10 production. The action of eugenol (50 or 100 µg/well) on IL-6 production prevented efficiently effects of LPS either before or after its addition, whereas on IL-10 production it counteracted significantly LPS action when added after LPS incubation.

Conclusions
Clove exerted immunomodulatory/anti-inflammatory effects by inhibiting LPS action. A possible mechanism of action probably involved the suppression of the nuclear factor-κB pathway by eugenol, since it was the major compound found in clove extract.
Mechanisms of action of zinc on rat intestinal epithelial electrogenic ion secretion: insights into its antidiarrhoeal actions
Authors: Bzik Victoria A , Medani Mekki , Baird Alan W , Winter Desmond C , Brayden David J 
Published: February 2012

Abstract

Objectives
Zinc is a useful addition to oral rehydration therapy for acute diarrhoea. We have assessed the mechanism of its epithelial antisecretory action when intestinal epithelial tight junctions were pharmacologically opened.

Methods
Rat isolated ileal and colonic mucosae were mounted in Ussing chambers and exposed to ZnSO4 (Zn2+) in the presence of secretagogues and inhibition of short circuit current (Isc) was measured.

Key findings
Pre-incubation with basolateral but not apical Zn2+ reduced Isc stimulated by forskolin, carbachol and A23187. In the presence of the tight junction-opener, cytochalasin D, antisecretory effects of apically-applied Zn2+ were enabled in colon and ileum. The apparent permeability coefficient (Papp) of Zn2+ was increased 1.4- and 2.4-fold across rat ileum and colon, respectively, by cytochalasin D. Basolateral addition of Zn2+ also reduced the Isc stimulated by nystatin in rat colon, confirming K channel inhibition. In comparison with other inhibitors, Zn2+ was a relatively weak blocker of basolateral KATP and K Ca2+ channels. Exposure of ileum and colon to Zn2+ for 60 min had minimal effects on epithelial histology.

Conclusions
Antisecretory effects of Zn2+ on intestinal epithelia arose in part through nonselective blockade of basolateral K channels, which was enabled when tight junctions were open.
Formulation development of gastroretentive tablets of lamivudine using the floating-bioadhesive potential of optimized polymer blends
Authors: Singh Bhupinder , Garg Babita , Chaturvedi Subhash Chand , Arora Sharry , Mandsaurwale Rachana , Kapil Rishi , Singh Baljinder 
Published: February 2012

Abstract

Objectives
The current studies entail successful formulation of optimized gastroretentive tablets of lamivudine using the floating-bioadhesive potential of carbomers and cellulosic polymers, and their subsequent in-vitro and in-vivo evaluation in animals and humans.

Methods
Effervescent floating-bioadhesive hydrophilic matrices were prepared and evaluated for in-vitro drug release, floatation and ex-vivo bioadhesive strength. The optimal composition of polymer blends was systematically chosen using central composite design and overlay plots. Pharmacokinetic studies were carried out in rabbits, and various levels of in-vitro/in-vivo correlation (IVIVC) were established. In-vivo gamma scintigraphic studies were performed in human volunteers using 99mTc to evaluate formulation retention in the gastric milieu.

Key findings
The optimized formulation exhibited excellent bioadhesive and floatational characteristics besides possessing adequate drug-release control and pharmacokinetic extension of plasma levels. The successful establishment of various levels of IVIVC substantiated the judicious choice of in-vitro dissolution media for simulating the in-vivo conditions. In-vivo gamma scintigraphic studies ratified the gastroretentive characteristics of the optimized formulation with a retention time of 5 h or more.

Conclusions
Besides unravelling the polymer synergism, the study helped in developing an optimal once-a-day gastroretentive drug delivery system with improved bioavailability potential exhibiting excellent swelling, floating and bioadhesive characteristics.
A herbal-drug interaction study of keishi-bukuryo-gan, a traditional herbal preparation used for menopausal symptoms, in healthy female volunteers
Authors: Saruwatari Junji , Takaishi Chisato , Yoshida Kousuke , Takashima Ayaka , Fujimura Youhei , Umemoto Yuichiro , Abe Tomohiro , Kitamado Masataka , Shimomasuda Masatsugu , Muramoto Yousuke , Nakagawa Kazuko 
Published: February 2012

Abstract

Objectives
Many patients use herbal medicines to relieve menopausal symptoms. Keishi-bukuryo-gan contains five herbal components, and has been used for treating hypermenorrhoea, dysmenorrhoea and menopausal symptoms in Asian countries. In this study, we investigated the potential herb–drug interactions of keishi-bukuryo-gan in healthy female subjects.

Methods
Thirty-one healthy females (20–27 years) were studied to evaluate their baseline activity of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) based on the urinary metabolic indices of an 8-h urine sample collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan, and also the urinary excretion ratio of 6β-hydroxycortisol to cortisol. Thereafter, the subjects received 3.75 g of keishi-bukuryo-gan twice daily for seven days, and underwent the same tests on post-dose day 7.

Key findings
The geometric mean phenotypic index for CYP1A2 significantly decreased by 16% on day 7 compared with the baseline (P = 0.026). Keishi-bukuryo-gan did not alter the indices for CYP2D6, CYP3A, XO and NAT2.

Conclusions
Keishi-bukuryo-gan may inhibit the activity of CYP1A2, which is predominantly involved in oestrogen metabolism. However, TJ-25 is unlikely to participate in herb–drug interactions involving medications predominantly metabolized by CYP2D6, CYP3A, XO and NAT2.
The effect of poloxamer 407 on the functional properties of HDL in mice
Authors: Yasuda Tomoyuki , Johnston Thomas P , Shinohara Masakazu , Inoue Michihiko , Ishida Tatsuro 
Published: February 2012

Abstract

Objectives
There is an inverse relationship between high-density lipoprotein (HDL) and heart disease. HDL possesses not only both antioxidant and anti-inflammatory properties, but also anti-thrombotic and endothelial function-promoting qualities. However, it is not only the serum concentration of HDL that is important, but also the ‘functional’ quality of the HDL. The objective was to determine the functional status of HDL in a well-established mouse model of dyslipidaemia and atherosclerosis induced by the administration of a block copolymer (poloxamer 407; P-407).

Methods
C57BL/6 mice were administered a single intraperitoneal dose of P-407 (0.5 g/kg) and blood was collected at 24 h post-dosing. HDL was isolated from controls (control HDL) and P-407-treated (P-407 HDL) mice and used to test its anti-inflammatory properties in vitro. Additionally, antioxidant enzymes associated with HDL, namely, platelet activating factor-acetylhydrolase (PAF-AH) and paraoxonase (PON), were evaluated for any potential reduction in their biological activity.

Key findings
A single injection of P-407 in C57BL/6 mice resulted in a marked decrease in the levels of HDL-cholesterol and phospholipids. HDL particle size significantly increased, primarily due to remodelling of HDL with triglyceride. It was demonstrated that (i) long-chain saturated fatty acids were higher and the n-3/n-6 fatty acid ratio was significantly lower for P-407 HDL compared with control HDL, and (ii) P-407 HDL lost its capacity to inhibit tumour necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expression compared with control HDL. Additionally, P-407 HDL was not able to neutralize lipopolysaccharide and inhibit subsequent TNF-α production compared with control HDL. The biological activity of platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase (PON) decreased in direct proportion to the circulating levels of both HDL-cholesterol and apolipoprotein (apoA-1).

Conclusions
Combination of previously reported findings in P-407-treated mice, such as (i) production of both oxidized LDL and malondialdehyde, and (ii) profound elevations in the soluble forms of intercellular adhesion molecule-1 (ICAM-1), VCAM-1, and E-selectin, with the present results, would strongly suggest that HDL in P-407-treated mice is rendered dysfunctional. Thus, these findings help to explain why P-407-treated mice begin to form aortic atherosclerotic lesions about one month after initiating P-407 treatment.
Platycodon grandiflorum modifies adipokines and the glucose uptake in high-fat diet in mice and L6 muscle cells
Authors: Ahn Young-Min , Kim Su Kang , Kang Ji-Suck , Lee Byung-Cheol 
Published: February 2012

Abstract

Objectives
Obesity and diabetes have become the most common human health problems worldwide. Obesity's contribution to type 2 diabetes might be due to dysregulation of adipokines and glucose uptake.

Methods
In this study, we performed in-vivo and in-vitro studies to evaluate the effects of Platycodon grandiflorum extract (PGE) on adipokines and glucose uptake. Before study, platycodin D concentrations were analysed by HPLC in PGE prepared in water, in 50% ethanol and in 80% ethanol, and we selected the 80% ethanol extract as the PGE for this study based on the HPLC results.

Key findings
We found that inclusion of PGE in the high-fat diet (HFD) markedly attenuated food intake, body weight, epididymal fat weight, adipocyte size and blood glucose levels by the oral glucose tolerance test in mice, and maintained serum levels of adiponectin, resistin, leptin, fructosamine and triglycerides. Gene expression analysis revealed that PGE up-regulated adiponectin, and down-regulated TNF-α and leptin in fat tissue. In L6 muscle cells in vitro, PGE increased insulin-stimulated glucose uptake.

Conclusions
We conclude that PGE may improve obesity in mice fed an HFD and glucose uptake in L6 muscle cells by modifying adipokines, and could offer clinical benefits as a supplement to treat obesity and diabetes.
Osteoarthritis of the knee and hip. Part I: aetiology and pathogenesis as a basis for pharmacotherapy
Authors: Adatia Aleem , Rainsford K D , Kean Walter F 
Published: February 2012

Abstract

Objectives
Osteoarthritis (OA) of the knee and hip is among the most frequent and debilitating arthritic conditions. Aside from surgical intervention in severe cases, conventional treatment involves relieving painful symptoms with non-steroidal anti-inflammatory drugs (NSAIDs), narcotic and non-narcotic (weak) analgesics and physical therapy. To obtain insight into the extent of pathological changes in hip and knee OA we reviewed current literature on the pathogenesis of this state as a basis for current pharmacotherapy options.

Key findings
Key features of the pathological joint changes in OA include: cartilage destruction by pro-inflammatory cytokines, matrix metalloproteinases and prostaglandins, which promote a catabolic environment; subchondral bone remodelling and resorption; hypertrophic differentiation of chondrocytes; neovascularisation of synovial tissue; and focal calcification of joint cartilage. Despite the central involvement of hyaline cartilage in OA pathogenesis, the source of pain likely stems from the richly innervated synovium, subchondral bone and periosteum components of the joint. Tissue damage during joint degeneration generates nociceptive stimuli. The presence of inflammatory mediators, including bradykinin, prostaglandins and leukotrienes, lowers the threshold of the Aδ and C pain fibres, resulting in a heightened response to painful stimuli.

Summary
It is our opinion that it is important to base and centre the management of OA patients on the severity of patient-important outcomes, rather than purely an assessment of damage to the joint. The joint damage, as interpreted from radiographs, is not necessarily representative of the symptoms experienced. The management of OA primarily comprises pharmacological therapy, surgical interventions and various non-pharmacological interventions.
Investigating paracetamol pharmacokinetics using venous and capillary blood and saliva sampling
Authors: Rittau Anneliese M , McLachlan Andrew J 
Published: February 2012

Abstract

Objective
The aim of this study was to develop, validate and apply a high performance liquid chromatography (HPLC) assay for analysis of paracetamol, paracetamol glucuronide and paracetamol sulfate in plasma (venous and capillary) and saliva to study paracetamol pharmacokinetics in healthy volunteers.

Methods
Samples were prepared using protein precipitation and analysed using reverse phase HPLC with UV detection. This assay was applied to venous and capillary plasma and saliva samples from 20 healthy volunteers after paracetamol 1 g four times daily for three days.

Key findings
The HPLC assay for paracetamol and its metabolites was found to be sensitive and selective in plasma and saliva samples over the range 0.05–50 mg/l with an inter- and intraday precision and accuracy within 11.2% and 11.1%, respectively. Mean recoveries for all analytes were &gt; 88%. A study of paracetamol pharmacokinetics in healthy volunteers found close agreement between the sampling matrices for paracetamol and metabolites (metabolites were not detected in saliva). The value for area under the concentration–time curve over the 6 h dosing interval of venous plasma (45.3 ± 12.9 mg/l.h) was significantly higher than that observed for capillary plasma (33.8 ± 12.9 mg/l.h) or saliva (35.1 ± 9.4 mg/l.h; P &gt; 0.01).

Conclusions
Capillary blood and saliva collection were found to be reliable sampling matrices for the evaluation of paracetamol pharmacokinetics, although paracetamol metabolites were not detected in saliva.