Plant latex thrombin-like cysteine proteases alleviates bleeding by bypassing factor VIII in murine model

Hemostasis is a tightly regulated process which maintains a fluid state of blood within the vasculature and provides thrombotic response upon tissue injury. Various scientific studies have implicated the role of plant latex proteases in hemostasis using in vitro experiments. However, in vivo models substantiate their role in hemostasis. Therefore, in the present study, the effect of plant latex thrombin-like proteases (PTLPs) on hemostasis was investigated systematically using mice tail bleeding as a preclinical model. In this direction, latex protease fractions (LPFs), which showed potent thrombin-like activity, were selected as they act directly on fibrinogen to form clot and quickly stop bleeding. Thrombin-like activity was exhibited mainly by cysteine proteases. Calotropis gigantea, Carica papaya, Jatropha curcas, Oxystelma esculentum, Tabernaemontana divaricata, and Vallaris solanacea LPFs and papain from C. papaya latex significantly reduced bleeding on a topical application in normal and aspirin administered mice. In addition, PTLPs accelerated the clotting of factor VIII deficient plasma, while, papain brought back the clotting time to normal levels acting like a bypassing agent. Further, papain failed to show activity in the presence of specific cysteine protease inhibitor iodoacetic acid; confirming protease role in all the activities exhibited. At the tested dose, PTLPs except C. gigantea did not show toxicity. Further, structural and sequence comparison between PTLPs and human thrombin revealed structural and sequence dissimilarity indicating their unique nature. The findings of the present study may open up a new avenue for considering PTLPs including papain in the treatment of bleeding wounds.     

The stochastic resonance of magnetosomes fixed in the cytoskeleton

The rotation of microscopic magnetic particles, magnetosomes, embedded into the cytoskeleton and subjected to a magnetic field and thermal noise was considered. The dynamics of magnetosome is shown to comply with the conditions of the stochastic resonance under not too tight constraints on the character of particle fastening. The excursion of regular rotations attains the value of the order of radian, which facilitates explaining the biological effects of low-frequency weak magnetic fields and geomagnetic fluctuations.     

Cardiovascular effects of transdermally delivered bupranolol in rabbits: effect of chemical penetration enhancers

Bupranolol is a promising candidate for transdermal drug delivery system (TDDS) development. The effect of permeation enhancers on the in vivo delivery and beta-blocking effect of reservoir type TDDS was studied in comparison with intravenous BPL in rabbits. The beta-blocking effect was quantified by measuring the inhibition of isoprenaline induced tachycardia in rabbits after BPL administration via transdermal and intravenous routes. The reservoir type TDDS containing a hydroxypropyl cellulose gel and polyethylene membrane was used as a control device. In comparison, the TDDS containing skin penetration enhancers, either 2-pyrrolidone or partially methylated beta cyclodextrin (PMbetaCD) were evaluated. The control device (no enhancer) produced about 52% inhibition of isoprenaline induced tachycardia at 2 h and the effect continued over 24 h application period, however, the devices with 2-pyrolidone or PMbetaCD produced about 85% inhibition of isoprenaline induced tachycardia at 3 h and the same effect continued over 24 h application period. Likewise, the AUC of these devices were significantly higher than that of control device. The intravenous bupranolol showed rapid decline in the pharmacodynamic effect with time indicating its rapid elimination. The in vivo delivery of bupranolol (as estimated by a mass balance study) from the devices made with pyrolidone or PMbetaCD was 3-fold higher than that of control. The results of this study strongly suggest that the penetration enhancers in the TDDS increased the in vivo delivery of BPL, thereby increased the beta-blocking activity of BPL by 50-60% higher than control, enabling the reduction of the TDDS patch size, accordingly.     

Plasmonically Tunable Blue-Shifted Emission from Coumarin 153 in Ag Nanostructure Random Media: A Demonstration of Fast Dynamic Surface-Enhanced Fluorescence

Enhancement of intensity and wavelength tunability of emission are desirable features for light-emitting device applications. We report on the large and tunable blue shift (60 nm) in emission from an environment-sensitive fluorophore (Coumarin153) embedded in Ag plasmonic random media. Coumarin 153 having emission at 555 nm, show a systematic blue shift (to 542, 503 and 495 nm) upon infiltration into random media fabricated by Ag nanowires of different aspect ratio (hence, surface plasmon resonances at 426, 445 and 464 nm). The blue shift is due to the fast dynamic surface-enhanced fluorescence mechanism and can be tuned by controlling the surface plasmon resonance and hotspot density in random media. Enhanced emission at desired wavelength is achieved by using nanostructures having higher extinction coefficient but same-surface plasmon resonance. Ag nanostructures of different aspect ratio used for fabricating the random media are synthesized by chemical route.     

Nanomedicine Scale-up Technologies: Feasibilities and Challenges

Nanomedicine refers to biomedical and pharmaceutical applications of nanosized cargos of drugs/vaccine/DNA therapeutics including nanoparticles, nanoclusters, and nanospheres. Such particles have unique characteristics related to their size, surface, drug loading, and targeting potential. They are widely used to combat disease by controlled delivery of bioactive(s) or for diagnosis of life-threatening problems in their very early stage. The bioactive agent can be combined with a diagnostic agent in a nanodevice for theragnostic applications. However, the formulation scientist faces numerous challenges related to their development, scale-up feasibilities, regulatory aspects, and commercialization. This article reviews recent progress in the method of development of nanoparticles with a focus on polymeric and lipid nanoparticles, their scale-up techniques, and challenges in their commercialization.KEY WORDS: lipid nanoparticles, nanomedicine, polymeric nanoparticles, scale-up production     

Enantioselective resolution of Rac‐terbutaline and evaluation of optically pure R‐terbutaline hydrochloride as an efficient anti‐asthmatic drug

Terbutaline is a β₂‐adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R‐isomer was found to be the potent enantiomer in generating therapeutic effect, while S‐isomer has been reported to show side effects. In this study, R‐terbutaline hydrochloride (R‐TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate (rac‐TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R‐TBH 6 nebulized solution was prepared in half dosage of Bricanyl®, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti‐asthmatic effect on guinea pigs via. pulmonary delivery. From the investigation, it is evident that R‐TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti‐asthmatic effect with Bricanyl®.     

Allelopathic effects ofParthenium hysterophorus L

Summary Growth inhibitors are washed down from the aerial vegetative parts ofParthenium hysterophorus L. during rain. These get adsorbed to soil particles thereby rendering the substratum inhibitory. The trichomes covering the vegetative parts contain inhibitors. The trichomes which get easily detached from dry parts when happen to settle on leaf surface of other plants in high quantity, reduce the chlorophyll and dry matter content in those species.Part I appeared in Plant and Soil53, 27 (1979).     

In vitro and in vivo evaluation of topical formulations of Spantide II

The purpose of this study was to develop and evaluate topical formulations of Spantide II, a neurokinin-1 receptor (NK-1R) antagonist, for the treatment of inflammatory skin disorders. Spantide II lotion and gel was formulated with and without n-methyl-2-pyrrolidone (NMP) as a penetration enhancer. The release of Spantide II from gels was evaluated using microporous polyethylene and polypropylene membranes in a Franz Diffusion cell setup. In vitro percutaneous absorption of Spantide II from lotion and gel formulations was evaluated using the above setup by replacing the membranes with hairless rat skin. The in vivo anti-inflammatory activity of Spantide II formulations was evaluated in an allergic contact dermatitis (ACD) mouse model. Among different gels studied, PF127 gel showed highest (70-fold) release of Spantide II compared with hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) gels. Lotion and gel formulations with or without NMP showed no detectable levels of Spantide II in the receiver compartment of the Franz diffusion cell until 24 hours. However, Spantide II showed significant retention in epidermis and dermis from lotion and gel formulations at 24 hours. The dermal levels increased ≈3.5- and 2-fold when the lotion and gel formulations contained NMP as compared with the formulation with no NMP (P<.05). The in vivo studies indicated that Spantide II formulations with NMP were effective in significantly reducing ACD response, similar to dexamethasone (0.5 mM). In conclusion, Spantide II was stable as a topical formulation and delivered to target skin tissue (epidermis and dermis) for the treatment of ACD. In addition this study supports the role of cutaneous neurosensory system in modulating inflammatory responses in the skin. Published: October 31, 2005     

The effect of progesterone replacement on gene expression in the corpus luteum during induced regression and late luteal phase in the bonnet monkey (<Emphasis Type="Italic">Macaca radiata</Emphasis>)

Background  

In higher primates, although LH/CG play a critical role in the control of corpus luteum (CL) function, the direct effects of progesterone (P4) in the maintenance of CL structure and function are unclear. Several experiments were conducted in the bonnet monkey to examine direct effects of P4 on gene expression changes in the CL, during induced luteolysis and the late luteal phase of natural cycles.     

Microwave absorption by magnetic nanoparticles in organisms

An estimate of the rate of absorption of the electromagnetic microwaves by magnetic nanoparticles in organisms is presented. The absorption takes place due to the energy dissipation at the ferromagnetic resonance. Based on the known solution of the Landau-Lifshitz equation, the imaginary part of the complex magnetic susceptibility is evaluated that gives the absorption rate. It is shown that even in the conditions of thermal isolation of the particles, their temperature growth would be insignificant at absorption of the emission with the energy flux density of the order of 1 mW/cm2, and the given mechanism is unrelated to the observable effects of low-intensity microwaves.