Process-structure-biofunctional paradigm in cellular structured implants: an overview and perspective on the synergy between additive manufacturing, bio-mechanical behaviour and biological functions.

The overview describes the synergy between biological sciences and cellular structures processed by additive manufacturing to elucidate the significance of cellular structured implants in eliminating stress shielding and in meeting the bio-mechanical property requirements of elastic modulus, impact resistance, and fatigue strength in conjunction with the biological functionality. The convergence of additive manufacturing, computer-aided design, and structure-property relationships is envisaged to provide the solution to the current day challenges in the biomedical arena. The traditional methods of fabrication of biomedical devices including casting and mechanical forming have limitations because of the mismatch in micro/microstructure, mechanical, and physical properties with the host site. Additive manufacturing of cellular structured alloys via electron beam melting and laser powder bed fusion has benefits of fabricating patient-specific design that is obtained from the computed tomography scan of the defect site. The discussion in the overview consists of two aspects - the first one describes the underlying reason that motivated 3D printing of implants from the perspective of minimising stress shielding together with the mechanical property requirements, where the mechanical properties of cellular structured implants depend on the cellular architecture and percentage cellular porosity. The second aspect focuses on the biological response of cellular structured devices.

A nearby long gamma-ray burst from a merger of compact objects.

Gamma-ray bursts (GRBs) are flashes of high-energy radiation arising from energetic cosmic explosions. Bursts of long (greater than two seconds) duration are produced by the core-collapse of massive stars1, and those of short (less than two seconds) duration by the merger of compact objects, such as two neutron stars2. A third class of events with hybrid high-energy properties was identified3, but never conclusively linked to a stellar progenitor. The lack of bright supernovae rules out typical core-collapse explosions4-6, but their distance scales prevent sensitive searches for direct signatures of a progenitor system. Only tentative evidence for a kilonova has been presented7,8. Here we report observations of the exceptionally bright GRB 211211A, which classify it as a hybrid event and constrain its distance scale to only 346 megaparsecs. Our measurements indicate that its lower-energy (from ultraviolet to near-infrared) counterpart is powered by a luminous (approximately 1042 erg per second) kilonova possibly formed in the ejecta of a compact object merger.

Augmentation of humoral and cellular immunity in response to Tetanus and Diphtheria toxoids by supercritical carbon dioxide extracts of Hippophae rhamnoides L. leaves.

Hippophae rhamnoides L. commonly known as Seabuckthorn (SBT), a wild shrub of family Elaegnacea, has extensively used for treating various ailments like skin diseases, jaundice, asthma, lung troubles. SBT leaves have been reported to possess several pharmacological properties including immunomodulatory, antioxidant, anti-inflammatory, antimicrobial and tissue regeneration etc. The present study was undertaken to evaluate the adjuvant property of supercritical carbon dioxide extracts (SCEs 300ET and 350ET) of SBT leaves in balb/c mice immunized with Tetanus and Diphtheria toxoids. The dynamic changes in the immune response were measured in terms of humoral and cell-mediated immune responses. We have seen the effect of SCEs on immunoglobulin subtypes and secondary immune response generation. In addition, the effect of SCEs on antigen specific cellular immunity was evaluated. Our results show that SCEs 300ET and 350ET significantly enhanced antibody titers in response to both TT and DT antigens. The secondary immune response generated was significantly increased in case of TT immunized animals. SCEs also enhanced cytokine levels (IFN-γ, IL-4, TNF-α and IL-1ß) and increased lymphoproliferation. Besides, both SCEs did not show any toxic effects. Therefore, the study suggests that SCEs are safe and have potent immunostimulatory activity and hence, seems to be a promising balanced Th1 and Th2 directing immunological adjuvant for various veterinary as well as human vaccines.

Variation in lipid and fatty acid uptake among nematode and cestode parasites and their host, domestic fowl: host-parasite interaction.

Lipid synthesis is an important process in most organisms as well as in helminths. The present observation shows the variation of lipid and fatty acid uptake among cestode, Raillietina (Fuhrmannetta) echinobothrida; nematode, Ascaridia galli and their host, Gallus domesticus, the common country fowl. Total lipid (TL), neutral lipid (NL), glycolipid (GL), phospholipid (PL) and their fatty acid of cestode, nematode and liver and intestinal fluid of the host were analyzed by thin layer chromatography and gas liquid chromatography respectively. The result shows that liver take more TL, PL and GL except NL. Utilization of lipid from intestinal fluid when compare between the parasites, it is found that TL and PL content of cestode are higher than nematode, whereas, nematode absorbs more NL and GL than cestode. The percent of cholesterol is more in cestode than nematode. Palmitic, stearic, oleic and linoleic are the predominant fatty acids among all the samples. The present study reveals that the cestode having large surface area is more opportunistic in the resource utilization over the nematode as well as the host.

Biology of Trypanosoma (Trypanozoon) evansi in experimental heterologous mammalian hosts.

Trypanosoma (Trypanozoon) evansi is a causative agent of the dreadful mammalian disease trypanosomiasis or 'Surra' and carried as a latent parasite in domestic cattle but occasionally proves fatal when transmitted to horses and camel. Sporadic outbreak of 'Surra' to different animals (beside their natural hosts) reminds that T. evansi may be zoonotic, as their close relative cause sleeping sickness to human being. This haemoflagellate is mechanically transmitted by horse fly and its effect on different host varies depending on certain factors including the effectiveness of transmission by mechanical vector, the suitability and susceptibility of the host as well as most importantly the ability of the disease establishment of parasite to adapt itself to the host's resistance, etc. The course of the disease caused by T. evansi is similar to that of human sleeping sickness caused by T. (T.) brucei gambiense. The target organs and symptoms show close similarity. T. evansi can successfully be transmitted among unnatural hosts i.e., other classes of vertebrates, like chicken. In transmission experiments, the unnatural hosts may sometimes induce profound changes in the biology of trypanosomes. Hence, in present study the observations are the biology of different morphological changes of T. evansi as well as its ability of disease formation within some heterologous mammal viz., albino rat, guineapig, bandicoot, mongoose, domestic cat and common monkey. Blood smears of infected albino rats, bandicoot, and mongoose revealed only monomorphic form. Interestingly, blood smears of infected cat and monkey, T. evansi shows slender trypomastigote form and short intermediate form whereas organ smears shows other two forms of haemoflagellate viz., sphaeromastigote and amastigote form. The haemoflagellate maintains a common reproductive cycle in all the experimental heterologous hosts whereas disease symptoms differ. T. evansi infected cat and monkey shows nervous symptoms. Infected monkey expresses some symptoms similar to that of human sleeping sickness disease. Thus the paper highlights zoonotic potentialities of T. evansi.

Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson's Disease.

Curcumin (CUR), a dietary polyphenol has diverse pharmacologic effects, but is limited by poor bioavailability. This is probably due to decreased solubility, cellular uptake and stability. In order to enhance its solubility and bioavailability, we synthesized the CUR bioconjugate curcumin monoglucoside (CMG) and tested its bioavailability, neuroprotective and anti-apoptotic propensity against rotenone (ROT) induced toxicity in N27 dopaminergic neuronal cells and Drosophila models. Our results elucidate that CMG showed improved bioavailability than CUR in N27 cells. Pre-treatment with CMG protected against ROT neurotoxicity and exerted antioxidant effects by replenishing cellular glutathione levels and significantly decreasing reactive species. CMG pre-treatment also restored mitochondrial complex I and IV activities inhibited by ROT. ROT-induced nuclear damage was also restored by CMG as confirmed by comet assay. CMG induced anti-apoptotic effects was substantiated by decreased phosporylation of JNK3 and c-jun, which in turn decreased the cleavage of pro-caspase 3. Q-PCR analysis of redox genes showed up-regulation of NOS2 and down-regulation of NQO1 upon ROT exposure and this was attenuated by CMG pre-treatment. Studies in the Drosophila ROT model revealed that, CMG administration showed better survival rate and locomotor activity, improved antioxidant activity and dopamine content than ROT treated group and was comparable with the CUR group. Based on these data, we surmise that CMG has improved bioavailability and offered neuroprotection comparable with CUR, against ROT-induced toxicity both in dopaminergic neuronal cell line and Drosophila models, with therapeutic implications for PD.

Comparison of fatty acid contents of the neutral and phospholipids of the trematode Paramphistomum cervi and liver of its host, Capra hircus.

The present observation records the lipid classes and their fatty acid composition of the neutral lipid and phospholipid of the trematode Paramphistomum cervi and liver of its host Capra hircus, the common Indian goat. Thin Layer Chromatography and Gas Liquid Chromatography were used to identify different neutral lipid and phospholipid components. The results show that among the neutral lipid fractions, the amount of combined hydrocarbon, wax ester and steryl ester is more or less equal in parasite and its host, but the percent of triacylglycerol is more in host liver than the parasite and the percent of total sterol is more in parasite than that of its host liver. Among the phospholipid fractions, phosphatidylinositol and phosphatidylethanolamine in the trematode parasite P. cervi and phosphatidylcholine and cardiolipin in the host's liver are the major components. The predominant fatty acids in the neutral lipid and phospholipid fractions of both the host liver and the trematode P. cervi include C16:0, C18:0, C18:1, and C18:2. The results reveal that the parasite P. cervi take up almost all the lipid and fatty acids from their host, which is required for their life cycle.

A supercritical CO2 extract from seabuckthorn leaves inhibits pro-inflammatory mediators via inhibition of mitogen activated protein kinase p38 and transcription factor nuclear factor-κB.

In the present study, we have demonstrated the anti-inflammatory properties of supercritical CO2 extract of seabuckthorn leaves (SCE) on mouse alveolar macrophage cell line (MH-S), human peripheral blood mononuclear cells (hPBMCs) in-vitro and in-vivo. Treatment of MH-S cells with SCE (0.5-100 µg/ml) significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production. It also inhibited the release of LPS-induced pro-inflammatory cytokines IL-6 and TNF-α, which was further confirmed by suppression of LPS induced TNF-α in hPBMCs by ELISPOT assay. In addition, western blot analysis demonstrated that SCE decreased LPS-induced inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in MH-S cells. Furthermore, SCE treatment also reduced nuclear factor-κB (NF-κB) translocation in nucleus induced by LPS in MH-S cells. To elucidate the molecular mechanism for inhibition of pro-inflammatory mediators by SCE (100 µg/ml), we further studied the effect of SCE on LPS-induced p38 mitogen-activated protein kinase (MAPK). It was observed that the phosphorylation of p38 MAPK in LPS-stimulated MH-S cells was significantly inhibited by SCE, which was further proven by suppression of LPS induced CD40 expression. The in-vivo model of AIA mice also showed a significant reduction in the inflammation of paw edema. These data collectively suggest that SCE suppressed the LPS-induced production of NO, IL-6, and TNF-α and expression of CD40, iNOS and COX-2 proteins by inhibiting NF-κB activation and phosphorylation of p38 MAPK. Hence, the SCE has potent anti-inflammatory activity and might be useful in chronic inflammatory diseases.

An extremely luminous panchromatic outburst from the nucleus of a distant galaxy.

Variable x-ray and γ-ray emission is characteristic of the most extreme physical processes in the universe. We present multiwavelength observations of a unique γ-ray-selected transient detected by the Swift satellite, accompanied by bright emission across the electromagnetic spectrum, and whose properties are unlike any previously observed source. We pinpoint the event to the center of a small, star-forming galaxy at redshift z = 0.3534. Its high-energy emission has lasted much longer than any γ-ray burst, whereas its peak luminosity was ∼100 times higher than bright active galactic nuclei. The association of the outburst with the center of its host galaxy suggests that this phenomenon has its origin in a rare mechanism involving the massive black hole in the nucleus of that galaxy.

Major lipids and fatty acids in the liver and rumen fluid of the goat (Capra hircus) infected with the trematode Paramphistomum cervi.

The present study records the occurrence of major lipid fractions and their fatty acids in a digenetic trematode parasite Paramphistomum cervi, and the rumen fluid and liver of the goat (Capra hircus). The amount of neutral lipids (NL), glycolipids (GL) and phospholipids (PL) of goat liver, rumen fluid and of the parasite shows that the rumen fluid is rich in NL, which is also in maximum quantity in the parasite, while the liver is rich in PL followed by NL. The number of fatty acids of total lipids (TL), NL and PL is greater in the parasite than those of the liver and rumen fluid. The number of fatty acids of GL is higher in the liver than in the parasite and the rumen fluid. Comparison of unsaturated fatty acid (UFA), C18 total and C18 UFA of TL, NL, GL and PL of the liver, rumen fluid and the parasite shows that the amount of C18 UFA is higher in P. cervi in all the lipid fractions, except for GL, than in the rumen fluid and the liver. The results reveal that P. cervi absorbs a greater number of fatty acids than its host.

Major lipid classes and their fatty acids in a parasitic nematode, Ascaridia galli.

The paper presents major lipid classes and their fatty acids investigated from Ascaridia galli, a nematode parasite of country fowl. Thin layer chromatography (TLC) reveals that the percent of total lipid, neutral lipid, phospholipids, and glycolipids are 1.94, 54.39, 26.95 and 18.66, respectively. Gas-liquid chromatography (GLC) analysis shows that the saturated fatty acids are the major components in all the lipid fractions followed by monoenes and dienes. Polyunsaturated fatty acids (PUFA) were present in low amount. Stearic acids (C(18)) were the chief components among all the fatty acids in all the lipid fractions.

Cardiology--a saga of one hundred years "but, where is the conductor?"--Braunwald, 2003.

Modern Cardiology was born with the birth of ECG invented by Einthoven in 1903. Since then a galaxy of great pioneers in succession led Cardiology through unprecedented landmark achievements to the present state which is as promising as challenging. This article reviews the journey of Cardiology as a speciality in the last one hundred years of its noteworthy life while highlighting the future directions and challenges the specialty is likely to face."

Effects of voluntary ethanol intake on the expression of Ca(2+) /calmodulin-dependent protein kinase IV and on CREB expression and phosphorylation in the rat nucleus accumbens.

To define the molecular basis of alcohol drinking behaviors, the effects of voluntary ethanol intake on the expression of Ca(2+)/calmodulin-dependent protein kinase IV (CaM kinase IV) and on the expression and phosphorylation of cAMP responsive element binding protein (CREB) [corrected] in the nucleus accumbens (NAc), central amygdala, and frontal cortex of rats were investigated. Voluntary ethanol intake significantly decreased the expression of CaM kinase IV and CREB phosphorylation but not of CREB protein levels [corrected], specifically in the shell of NAc. These changes were not observed in the core of NAc, central amygdala and frontal cortex. Mianserin treatment significantly attenuated ethanol intake and antagonized the voluntary ethanol-induced reduction in expression of CaM kinase IV and CREB phosphorylation in the shell of NAc. This is the first evidence to suggest that decreased CaM kinase IV-dependent CREB phosphorylation in the shell region of NAc may play a role in the reward mechanisms of alcohol drinking.

Laboratory and field evaluation of measurement methods for one-hour exposures to O3, PM2.5, and CO.

While researchers have linked acute (less than 12-hr) ambient O3, PM2.5, and CO concentrations to a variety of adverse health effects, few studies have characterized short-term exposures to these air pollutants, in part due to the lack of sensitive, accurate, and precise sampling technologies. In this paper, we present results from the laboratory and field evaluation of several new (or modified) samplers used in the "roll-around" system (RAS), which was developed to measure 1-hr O3, PM2.5, and CO exposures simultaneously. All the field evaluation data were collected during two sampling seasons: the summer of 1998 and the winter of 1999. To measure 1-hr O3 exposures, a new active O3 sampler was developed that uses two nitrite-coated filters to measure O3 concentrations. Laboratory chamber tests found that the active O3 sampler performed extremely well, with a collection efficiency of 0.96 that did not vary with temperature or relative humidity (RH). In field collocation comparisons with a reference UV photometric monitor, the active O3 sampler had an effective collection efficiency ranging between 0.92 and 0.96 and a precision for 1-hr measurements ranging between 4 and 6 parts per billion (ppb). The limits of detection (LOD) of this method were 9 ppb-hr for the chamber tests and approximtely 16 ppb-hr for the field comparison tests. PM2.5 and CO concentrations were measured using modified continuous monitors--the DustTrak and the Langan, respectively. A size-selective inlet and a Nafion dryer were placed upstream of the DustTrak inlet to remove particles with aerodynamic diameters greater than 2.5 microm and to dry particles prior to the measurements, respectively. During the field validation tests, the DustTrak consistently reported higher PM2.5 concentrations than those obtained by the collocated 12-hr PM2.5 PEM samples, by approximately a factor of 2. After the DustTrak response was corrected (correction factor of 2.07 in the summer and 2.02 in the winter), measurements obtained using these methods agreed well with R2 values of 0.87 in the summer and 0.81 in the winter. The results showed that the DustTrak can be used along with integrated measurements to measure the temporal and spatial variation in PM2.5 exposures. Finally, during the field validation tests, CO concentrations measured using the Langan were strongly correlated with those obtained using the reference method when the CO levels were above the LOD of the instrument [approximately 1 part per million (ppm)].

Syntheses of Curcumin Bioconjugates and Study of Their Antibacterial Activities against beta-Lactamase-Producing Microorganisms.

In the present study curcumin bioconjugates, viz. di-O-glycinoylcurcumin (I), di-O-glycinoyl-C(4)-glycylcurcumin (II), 5'-deoxy-5'-curcuminylthymidine (5'-cur-T) (IV), and 2'-deoxy-2'-curcuminyluridine (2'-cur-U) (V) have been synthesized and characterized by elemental analysis and (1)H NMR. The turmeric peptide (Tp) was isolated from the aqueous turmeric extract of the turmeric rhizome. The antibacterial activity of these four bioconjugates and also of the turmeric peptide and sodium salt of curcumin (III) have been tested particularly for beta-lactamase-producing microorganisms.

Study on curcumin-oligonucleotide conjugate as a probable anticancer agent: its hybridisation with telomere target sequence 5'-GGGATTGGGATT-3'.

Curcumin-oligonucleotide conjugate was synthesised by attaching diglycyl conjugate of curcumin to 12-mer complementary telomere sequence 5'-AATCCCAATCCC-3'. An enhanced Tm of 6 degrees C was found, showing high affinity for the target strand. This may be exploited for the suppression of cancer i.e. by blocking the expression of telomere sequence [GGGATT]n repeats.

Lymphatic filariasis of the ovary and mesosalpinx.

We report 2 cases of filariasis, one in the ovary and the other in the mesosalpinx. In the first case, the patient underwent panhystrectomy and in the second case, right ovarian cystectomy with right salpingectomy were performed under general anaesthesia. Histopathology showed adult filarial worms in the dilated lymphatics of the right ovary, in the first case and in the mesosalpinx, in the second case. Both patients presented with complaints related to gynecological problems and not filariasis. Reports of filariasis in the literature and possible treatments and prevention strategies are also discussed.

Histopathology of Trypanosoma (Trypanozoon) evansi infection in bandicoot rat. I. visceral organs.

Experimental infection of Trypanosoma (Trypanozoon) evansi in Bandicota bengalensis produces an acute disease course leading to untimely death of the bandicoot rat. The sequential alteration of liver, spleen, lung, kidney, and heart was studied on the 5th, 8th, 12th, and 14th days postinoculation. The rats showed inflammatory, degenerative, and necrotic changes in these organs. In liver, pseudolobule formation, necrosis and hemorrhage within the sinusoids, and fatty degeneration of hepatic cells were the predominant histopathological changes. The changes were destructive and irreversible. In spleen giant cells aggregation and granulomatous lesion, i.e., accumulation of histiocytes, were the protective changes, whereas tissue and cell damage indicated irreversible degeneration. The gradual development of intrabronchus inflammation, aggregation of inflammatory cells around the alveoli, congestion of bronchioles, septal edema, atrophy of alveolar walls, migration of macrophages, and emphysema were the histopathological changes noticed in the lungs of the infected rats. The affected kidney showed infiltration of lymphocytes, hemorrhage in the interlobular space, and glomerulitis as the irreversible and destructive changes in the rats. There was degeneration of myocardium in the hearts of the rats. The histopathological changes in these organs are compared with those studied in surra, human sleeping sickness disease, and African trypanosomiasis. Possible mechanisms for these histological changes in the visceral organs are discussed.

Synthesis of terminally labelled RNA sequences: fluorescence and hybridisation study of RNA-DNA duplexes.

A stable and suitably labelled DNA-RNA hybrid, resistant to RNAse degradation has been prepared by hybridising the RNA sequence carrying methoxy group at 2'-position of ribose moiety in adenosines and labelled with dansyl group attached via a linker at the terminal uridyl unit. Study may be useful in sequencing and targeting specific viral sequences.