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The current study describes the development of a wireless controlled iontophoretic drug delivery system. The control system was made using ZigBee communication protocol. The performance analysis of the current injecting circuit was performed to ascertain minimal error combined with high efficiency. Finally, the developed controlled system was used to manipulate the functioning of the two independent iontophoretic drug delivery systems. In gist, a wireless controlled drug delivery system based on ZigBee communication protocol was developed and tested successfully.

Pueraria tuberosa is known for its therapeutic potentials in cardiovascular disorders, but its effect in angiogenesis has not been studied so far. In this study, a computational approach has been applied to elucidate the role of the phytochemicals in inhibition of angiogenesis through modulation of vascular endothelial growth factor receptors: Vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, major factors responsible for angiogenesis. Metabolite structures retrieved from PubChem and KNApSAcK - 3D databases, were docked using AutoDock4.2 tool. Hydrogen bond and molecular docking, absorption, distribution, metabolism and excretion and toxicity predictions were carried out using UCSF Chimera, LigPlot(+) and PreADMET server, respectively. From the docking analysis, it was observed that puerarone and tuberostan had significant binding affinity for the intracellular kinase domain of vascular endothelial growth factor receptors-1 and vascular endothelial growth factor receptor-2 respectively. It is important to mention that both the phytochemicals shared similar interaction profile as that of standard inhibitors of vascular endothelial growth factor receptors. Also, both puerarone and tuberostan interacted with Lys861/Lys868 (adenosine 5'-triphosphate binding site of vascular endothelial growth factor receptors-1/vascular endothelial growth factor receptors-2), thus providing a clue that they may enforce their inhibitory effect by blocking the adenosine 5'-triphosphate binding domain of vascular endothelial growth factor receptors. Moreover, these molecules exhibited good drug-likeness, absorption, distribution, metabolism and excretion properties without any carcinogenic and toxic effects. The interaction pattern of the puerarone and tuberostan may provide a hint for a novel drug design for vascular endothelial growth factor tyrosine kinase receptors with better specificity to treat angiogenic disorders.

Biomaterial induced activation of vascular endothelial growth factor (VEGF) pathway for angiogenesis is now gaining recognition as an effective option for tissue engineering. In this context, bivalent nickel (Ni2+) ion doped nano-hydroxyapatites (nHAp) were synthesized by wet chemical method, characterized and evaluated for their osteoconductive and proangiogenic properties. Electron microscopy (FESEM and TEM) along with ICP-OES analysis ensured formation of Ni2+ doped nanoparticles (average ferret diameter 15–17 nm). The ‘apatite identity’ of the nanoparticles was confirmed by XRD and FT-IR. Analysis revealed that Ni2+ doping caused no significant distortion in the crystal structure but decreased the crystallinity of nHAp considerably. Similarly, no major variation in the surface area (BET analysis), the zeta potential and the protein adsorption was observed among the samples. Biological characterization showed that Ni2+ doping influenced the cell viability, proliferation and differentiation of bone cells (MG-63) in a concentration dependent way. ELISA and RT-PCR study revealed that Ni2+ doped nHAp induced cellular VEGF expression many fold in comparison to control. Profiling of hypoxia inducible factor 1 alpha (HIF-1α) expression by immuno-cytochemistry and RT-PCR implied its involvement in cellular VEGF production. In conclusion, Ni2+ doped nHAp may serve as proangiogenic–osteogenic biomaterial for bone tissue engineering.

This paper presents a framework to explore the effect of music (motivational song) on cardiac physiology using recurrence analysis. For the characterization of the ECG signals, recurrence has been reported to be an effective tool. This non-linear dynamic method has been considered economical than other computational methods. The ECG data were acquired from eighteen male volunteers. The signals were further processed to extract the R-R intervals (RRI). Recurrence analysis of the ECG and the RRI signals suggested a reduction in the isometric recurrence in the post-stimulus condition, and hence, a corresponding increase in the heart rate variability. The variation was also evidenced from the ANN classification of the ECG and the RRI signals with efficiency of ≥ 85%.

The current study deals with the preparation and the characterization of the PVA-CMT-GO films. The PVA-CMT film was translucent in nature and smooth to touch. The addition of GO resulted in the formation of agglomerated structures. XRD studies suggested that the incorporation of GO increased the average crystallite size. The mechanical properties of the films as determined by stress relaxation studies suggested that all the films were viscoelastic in nature. The drug release study showed a decrease in the amount of the drug release with the increase in the GO content. The PVA-CMT-GO films (without drug) showed certain degree of antimicrobial activity owing to the inherent antimicrobial property of GO. The drug loaded films also showed good antimicrobial property. It was found that the prepared films altered the cell proliferation of the human skin keratinocytes in a composition-dependent manner.

There is a pressing need for a ubiquitously expressed antigen or receptor on the tumor surface for successful mitigation of the deleterious side effects of chemotherapy. Phosphatidylserine (PS), normally constrained to the intracellular surface, is exposed on the external surface of tumors and most tumorigenic cell lines. Here we report that a novel PS-targeting liposome, phosphatidylcholine-stearylamine (PC-SA), induced apoptosis and showed potent anticancer effects as a single agent against a majority of cancer cell lines. We experimentally proved that this was due to a strong affinity for and direct interaction of these liposomes with PS. Complexation of the chemotherapeutic drugs doxorubicin and camptothecin in these vesicles demonstrated a manyfold enhancement in the efficacies of the drugs both in vitro and across three advanced tumor models without any signs of toxicity. Both free and drug-loaded liposomes were maximally confined to the tumor site with low tissue concentration. These data indicate that PC-SA is a unique and promising liposome that, alone and as a combination therapy, has anticancer potential across a wide range of cancer types.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the synovial joints of the body. Methotrexate (MTX) is considered as a mainstay in the management of RA. However, monotherapy with MTX in RA is often limited by potential long-term toxicity. The present study was conducted to evaluate if MTX-pioglitazone combination therapy has an add-on benefit over monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in adjuvant-induced arthritis model. MATERIALS AND METHODS: Arthritis was induced by single subcutaneous injection of complete Freund's adjuvant (CFA) in thirty male Wistar albino rats. They were then divided into five equal groups, which included two control groups (arthritic and nonarthritic), pioglitazone-treated (1.35 mg/kg daily), MTX-treated (0.225 mg/kg daily), and MTX + pioglitazone-treated. The disease-modifying action of the drugs was assessed by various physiological, hematological, and biochemical parameters along with histopathological and radiological analysis of affected joints. The experimental data were statistically assessed by one-way ANOVA. RESULTS: There was a significant reduction of disease activity in the MTX monotherapy group when compared with disease control. However, pioglitazone monotherapy group failed to demonstrate any significant effect on disease activity. The MTX-pioglitazone combination group demonstrated greater suppression of disease activity as compared to MTX and pioglitazone monotherapy and disease control group (P < 0.05). CONCLUSION: The present study demonstrates that the combination therapy of MTX with pioglitazone offers better control of disease activities in RA as compared to MTX or pioglitazone monotherapy.

Background: In 2018, Medical Council of India (MCI) recommended competency-based medical education (CBME) for medical undergraduates. Aim and objective: A questionnaire-based study was conducted to assess the perceptions and preparedness of pharmacology faculties on CBME. Materials and Methods: The study was conducted among pharmacology faculties selected on basis of any one or more of the following criteria: (1) Faculties who attended the national faculty development program conducted by MCI and (2) Members of Indian Society for Rational Pharmacotherapeutics. The questionnaire was made available through Google doc online platform which was e-mailed/WhatsApp to selected participants. It included questions related to components of the curriculum, namely, objectives, teaching–learning methods, and integration of disciplines. The responses received were analyzed in Microsoft Excel sheet using descriptive statistics. Results: Questionnaire was sent to 1424 participants out of which 144 (10.1%) responded. Majority (27.8%) had 6–10 years of postgraduate teaching experience. A total of 130 (90.3%) respondents were aware of CBME; sensitization workshops, continuing medical education (CME), etc., (41.5%) being most frequent source of information. Half of respondents (49.2%) were prepared to implement the curriculum, while 26 (20.0%) were not. The lack of training about CBME was the most cited reason for nonpreparedness. Majority (64.6%) of the respondents (84/130) considered horizontal and vertical integration to implement the new curriculum is feasible. However, most of them (70.8%) expressed reduction in teaching hours will be inadequate to complete pharmacology syllabus. On a scale of ten, the average rating of the respondents for new curriculum (6.83) did not show any statistical difference against old one (6.25). Conclusion: In our study, most of the participants welcome the new curriculum, although majority suggested need for training and guidance. To further understand the requirements, national organizations like MCI may conduct larger studies in the wide network of institutes.

99mTc-paclitaxel was synthesized by using sodium borohydride as a reducing agent. Greater than 95 % labelling efficiency was achieved. Radiochemical purity of the synthesized 99mTc-paclitaxel was validated by thin layer chromatography (TLC) scanner and high performance liquid chromatography (HPLC). 99mTc-paclitaxel passed in vitro stability tests. Biodistribution and scintigraphy studies were performed in Sprague–Dawley rats. The biodistribution study results of 99mTc-paclitaxel were related mainly to the metabolism and excretion routes followed by the parental drug, paclitaxel. Apart from that, biodistribution of 99mTc-paclitaxel was altered after pre-treatment with cold paclitaxel. Hence, 99mTc-paclitaxel may be used as a tracer for paclitaxel.

Flu mimics damaged proteins during entry Viruses are master manipulators. The early stages of how flu viruses enter cells are very well understood, but Banerjee et al. describe a new wrinkle (see the Perspective by Rajsbaum and García-Sastre). It seems that the virus carries with it into the cell ubiquitin: a molecule involved in marking proteins for destruction. The virus then exploits host cell machinery involved in recognizing and dealing with damaged proteins to uncoat its own RNA genome, ready to continue its path toward successful infection. Science , this issue p. 473 ; see also p. 427

Nanoparticle biodistribution study is of great importance in bringing nanomedicine to patients. In this article, solid lipid nanoparticle (SLN) with dimension less than 100 nm was successfully radiolabelled with 99mTc by using sodium borohydride as a reducing agent (instead of stannous salts). Paclitaxel (PTX) was used as a model anticancer drug for the preparation of drug loaded SLN (PSLN). PSLN was characterized by standard methods. Encapsulation efficiency for PTX in PSLN was estimated by HPLC. PTX (Taxol formulation) and PSLN were radiolabelled separately and subsequent characterizations of these complexes were performed. Greater than 95 % radiolabelling efficiency was achieved and the labelling efficiency was calculated to be more than 90 % upto 24 h. Both the above-mentioned complexes passed the in vitro stability tests. PSLN achieved more brain concentration than Taxol as determined by biodistribution studies. This type of radiolabelling technique can be useful in preclinical evaluation of drug loaded SLN.

The aim of this study was to synthesis, a radiolabeled (99mTc) new somatostatin-analogue 6-hydrazinopyridine-3-carboxylic-acid (HYNIC)-Asn3-octreotate (99mTc-HYNIC-AATE), and to evaluate as a candidate for imaging somatostatin-receptor (SSTR)-positive tumors and also compare it with 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC). Synthesis was performed by Fmoc-solid-phase strategy and 99mTc labeled by SnCl2. Biodistribution and imaging properties of new radiopeptide were also studied in C6 tumor bearing rat. Radiolabeling was performed at high specific activities and it showed high binding-affinity for SSTR2. In biodistribution, radiopeptides have showed high and receptor-specific uptake in the SSTR2 positive organs, tumor with rapid renal excretion from non-target tissues. These results demonstrated that 99mTc-HYNIC-AATE is a new specific radioligand for scintigraphy of somatostatin-receptor-positive tumors.

Introduction: The high death rate due to breast cancer is often attributed to aggressive triple negative breast cancer (TNBC). We used the combination of metronomic pegylated liposomal doxorubicin (PLD), and metformin {selectively inhibits cancer stem cells (CSCs)} for effective management of TNBC xenografts generated in mice. Down-regulation of β-catenin is responsible for the efficacy of the combination of metronomic PLD and metformin in treating aggressive TNBC. Methodology: PLD was prepared using the ammonium sulfate gradient method. Morphology, particle size, zeta potential measurement, drug entrapment efficiency, and drug release studies were performed to characterize the prepared liposomal formulation. Cell culture studies were performed on MDA-MB-231 and MDA-MB-468 cell lines (i.e., TNBC cells). MTT assays, mammosphere assays, apoptosis assays, quantitative real-time polymerase chain reactions (qPCR), western blotting experiments were performed. In vivo anticancer efficacy of the combination therapy {antidiabetic dosing of metformin: 150 mg/kg body weight every day, and metronomic dosing of PLD: 1 mg/kg body weight with respect to doxorubicin (Dox) every other day for 3 weeks} was verified in an MDA-MB-231 xenograft model. Results: Monodisperse PLD having dimensions less than 100 nm was successfully prepared (confirmed by AFM, TEM, and DLS). Zeta potential measurement showed that PLD was negatively charged (- 12.1 ± 2.3 mV, n = 3). Encapsulation efficiency and drug release were found to be satisfactory. IC50 (i.e., 50 % inhibitory concentration) of PLD was found to be in nanomolar range with respect to Dox in TNBC cell lines. However, a combination of metformin (500 µM) and PLD resulted in a leftward shift of the concentration-response curve such that the IC50 value of PLD was further reduced in the nanomolar range with respect to Dox. A similar trend was seen in the apoptosis assay. Metformin works together with PLD to reduce non-stem cancer cells, CSCs, and stem cell markers as indicated by the reduction in the number of mammospheres, qPCR results, and western blotting experiments. We also found attenuation of β-catenin in TNBC cells by the combination treatment regimen, as suggested by qPCR and western blotting. Some of the in vitro observations were also confirmed in the MDA-MB-231 xenograft model. Conclusion: Our experiments demonstrate that down-regulation of β-catenin is responsible for the strong anticancer effects of the combination of metformin and PLD in vitro and in vivo. Further studies are warranted with this combination regimen in different cancer types as metformin is an approved anti-diabetic drug with an acceptable safety profile, and metronomic chemotherapy is gaining popularity in treating different cancer types. Citation Format: Indranil Banerjee, Subhayan Das, Chandan Kanta Das, Bikash Ch. Jena, Deblina Bharadwaj, Anjan K. Pradhan, Swadesh K. Das, Paul B. Fisher, Mahitosh Mandal. Combination of metformin and metronomic liposomal doxorubicin exerts a robust anticancer effect in triple negative breast cancer by inhibiting breast cancer stem cells & the Wnt/beta-catenin pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3638.

Introduction: Biochemical crosstalk between tumor and stroma by several secretory factors has evolved as a significant contributor for the development of therapeutic resistance in breast cancer, where cancer-associated fibroblasts (CAFs) in the tumor stroma play a critical role. However, the role of secretory factors of cancer cells in assisting CAF chemoresistance is least apparent. TGF-β is the major cytokine secreted by the cancer cells to the tumor stroma that further imparts resistance in CAFs to the chemotherapy. Here, we hypothesize that tamoxifen-resistant breast cancer cells stimulate surrounding CAFs towards chemoresistant phenotype through TGF-β1 activated p44/42 MAPK signaling pathway. Methodology: The tamoxifen-resistant (TAM-R) clones of parental MCF-7 cell line were established by treating with sub-lethal doses over several cycles and characterized by MTT assay. Western blot (WB) was performed to quantify the TGF-β1 expression in the parental MCF-7 and the resistant MCF-7 (MCF-7/TAM-R) cells. ELISA was carried out to quantify TGF-β1 in the conditioned media (CM) from MCF-7 and MCF-7/TAM-R. CM from both the MCF-7 and MCF-7/TAM-R was collected and treated to the fibroblasts in dose and time-dependent manner. Initial screening for the expression of CAF markers α-SMA and caveolin-1 was carried out by qPCR and confirmed by WB. Cell cycle analysis was performed by flow cytometry and WB. Scratch assay was performed to evaluate migration and proliferation activity of CAFs. Downstream signaling pathway analysis was carried out by WB. Expression of TGF-β1 and p44/42 was downregulated by appropriate inhibitors. Results: Tamoxifen treatment to the MCF-7 cells showed a marked increase in TGF- β1 expression both in time and dose-dependent manner. α-SMA was upregulated, and Caveolin-1 was downregulated in CAFs after treatment of CM from MCF-7/ TAM-R cells. MTT result showed a higher IC50 value of TAM in CAFs treated with CM compared to untreated one. WB analysis confirmed the elevated anti-apoptotic and reduced pro-apoptotic protein expressions in CAFs post-treatment. Flow cytometry analysis depicts less number of cells in the sub G0/G1 phage after TAM treatment in CM treated CAFs compared to untreated one. WB results showed increased cyclin D1, and cyclin E in CM treated CAFs. Further, inhibiting TGF- β1 in MCF-7/TAM-R cells and p44/42 MAPK signaling cascade in CM treated CAFs found a strong correlation between the elevated expressions of TGF- β1 in MCF-7/TAM-R cells and p44/42 signaling pathway in CM treated CAFs. Conclusion: Here we report that chemoresistant breast cancer cells with increased TGF- β1 expression exhibit a greater potential in inducing TAM resistance in CAFs compared to parental cells, with an up-regulated p44/42 MAPK signaling cascade. The mechanism underscores the p44/42 MAPK signaling pathway as an important therapeutic target in tumor stroma. Note: This abstract was not presented at the meeting. Citation Format: Bikash Chandra Jena, Chandan Kanta Das, Deblina Bharadwaj, Subhayan Das, Indranil Banerjee, Santosh Gupta, Mahitosh Mandal. Paracrine TGF-β1 induces tamoxifen resistance in cancer-associated fibroblsts by activation of p44/42 MAPK signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 120.

Congenital anomalies of the female reproductive tract may involve the uterus, cervix, fallopian tubes, or vagina. Depending on the specific defect, a woman’s obstetric and gynecologic health may be adversely affected. In the present series patients presenting in the outpatient department with diagnosed Mullerian abnormalities were classified into several categories based on their presenting complaints. These patients were offered proper judicious management and were followed up as required. After one year of study period it was clear that most of these patients (barring a few exceptions) were treated optimally and they could live a healthy lifestyle thereafter.

Background: Prescription is the written order of the physician which is conveyed to the patient. Rational prescription writing is a skill which should be mastered at the earliest. Internship is the period where undergraduate medical education can be consolidated through continued learning under the direct supervision of teachers. The attitude of interns toward rational drug use is of utmost importance. The present study aimed to explore the prescribing pattern of interns in a primary health center in India. Materials and Methods: A cross-sectional study was conducted for a period of 2 months (June 1 2010-July 30 2010) in a primary health center attached to a medical college in India. The main outcome measure was to assess rationality of prescribing pattern of interns was measured as per World Health Organization enlisted prescribing indicators. Data analysis was done by using descriptive and inferential statistical methods: Frequencies, percentage, and mean standard deviation. Results: A total of 1968 drugs were prescribed in 760 prescriptions analyzed with an average of 2.58 drugs per prescription. Analgesic was the most commonly prescribed drug (25.78%) followed by antibiotics (22.1%), drugs used for gastrointestinal symptom (15.78%), multivitamins (11.84%), anti-malarials (8.35%), antihistaminics (6.25%), and hematinics (5.36%). Regarding prescribing indicators, in 435 prescriptions (22.4%), antibiotics were advised. A total of 688 (34.97%) drugs were prescribed by generic name, while the percentage of drugs prescribed from essential drug list of India was 58.47%. Injectables were prescribed in 89 prescriptions (4.49%). Conclusion: The present study shows that irrational prescribing practices are common among interns of the institute. The art of rational prescribing should be taught to them by medical teachers who are adequately trained in rational drug use.

Over the last two decades, organogels have found tremendous use in the pharmaceutical, food, and cosmetics industries with notable developments as drug delivery matrices and trans and saturated fat replacers in processed foods. The functionality of organogels benefits from their ease of preparation, cost effectiveness, and ability to contain both hydrophilic and lipophilic constituents. This review provides thorough insight into different organogelators, their mechanisms of organogel formation, various characterization techniques and their biocompatibility when administered in vivo. Finally, a special treatise is given on the applications of organogels as controlled drug delivery vehicles for topical, dermal/transdermal, parenteral, oral, and nasal routes. In situ forming organogels and their potential for tailored release of incorporated active ingredients are also discussed.

Introduction: Fluoxetine is a commonly prescribed drug which is used in the psychiatric practice and adenomyosis is a common medical problem in women of the reproductive age group. Objective: To explore the role of fluoxetine in the causation of adenomyosis. Methods: Female Wistar rats (n=18) were divided into three groups (group I (the control), group II and group III) and they were treated with normal saline and oral fluoxetine (4mg/kg and 8 mg/kg) respectively for 100 days. Periodic serum prolactin measurements and histopathological examinations of the uterine horns of all the rats were done at the end. Comparison of the mean serum prolactin levels between the patients (n=15) who were diagnosed with adenomyosis, the healthy age sex matched controls and the female patients (n=20) who received fluoxetine for more than 3 months, before and after the fluoxetine administration, was done separately. Appropriate (paired or unpaired) t tests were used for the data analysis. Results: Out of the 12 test group rats, 10 rats showed the features of adenomyosis histopathologically, along with significantly (p < 0.05) raised serum prolactin levels. The mean serum prolactin levels of the patients of adenomyosis in comparison to those of the controls and of the patients who were treated with fluoxetine (before and after the fluoxetine administration), were significantly high (p=0.001 in both the cases). Conclusion: Fluoxetine may have some role in the causation of adenomyosis; although for a stronger evidence, the follow-up of the patients who are treated with fluoxetine on a long term basis should be ideal.

Considering the fact that life on Earth is carbon based, carbon materials are being introduced in biological systems. However, very limited information exists concerning the potential effects of different structures of carbon materials on biological systems. In the present study, poly(lactic-co-glycolic acid) (PLGA)-based carbonaceous composites were developed by reinforcing 1 wt% of three different carbon-based materials i.e. carbon nanotubes (CNTs-1D), graphene nanoplatelets (GNPs-2D), and activated carbon (AC-3D). The developed composites were characterized for physicochemical, biological, and mechanical properties. Along with their hemocompatible nature, the composites exhibited better swelling ratio, degradation percentage, bioactivity, and tensile strength. The improvement in hydrophilicity and protein adsorption resulted in the enhancement of cell proliferation and differentiation. Overall, sheet-like GNPs showed the strongest effect on the composite's properties due to their larger exposed area. These results demonstrate the potential of PLGA-based carbonaceous composites for accelerating bone tissue regeneration.

There is a dearth of evidence on the safety of the use of antipsychotics during pregnancy. Olanzapine, a pregnancy category C drug, has no unequivocal evidence of harm to the fetus. Against this backdrop, we report the first case of a tracheo-esophageal fistula (TEF) in a newborn following maternal antenatal exposure to olanzapine. A 29-year-old woman with acute psychotic disorder had been treated with olanzapine for the last 7 years. Her first pregnancy, while taking olanzapine, resulted in a miscarriage at 4 months’ gestation, following which she discontinued olanzapine. She reconceived after a few months and delivered a full-term normal child. However, due to the recurrence of psychiatric illness after her second pregnancy, she was prescribed olanzapine again, which was continued throughout her third pregnancy. The outcome of the third pregnancy was a full-term female baby with a TEF. The baby was managed surgically and discharged with satisfactory vital signs. Unfortunately, however, the baby did not survive beyond 11 months of age. Causality between antenatal maternal olanzapine exposure and TEF in the newborn was determined to be ‘probable’ (score +5) as per the Naranjo causality assessment scale. Greater knowledge of this potential teratogenicity caused by olanzapine is needed to reduce morbidity and mortality in newborns.

The present study reports the analysis of the properties of the tamarind gum based hydroethanolic physical hydrogels. The extent of hydrogen bonding in the hydrogels decreased with the increase in the tamarind gum content. The hydrogel with the highest tamarind gum content was found to be highly stable in terms of mechanical properties. There was a decrease in the resistive component of the hydrogels with the increase in the tamarind gum content. The drug release from the hydrogels increased with the increase in the tamarind gum content. The antimicrobial activity of the drug-loaded hydrogels against E. coli was excellent.

The present study reports the in-depth analysis of the gelatin–carboxymethyl chitosan hydrogels. The composite system formed phase-separated hydrogels, which is confirmed by scanning electron microscopy. The swelling of the carboxymethyl chitosan-containing hydrogels was lower than the gelatin hydrogel. Macroscale deformation study using a static mechanical tester indicated a viscoelastic nature of the hydrogels. A decrease in the impedance of the hydrogels was observed with an increase in the carboxymethyl chitosan content. The drug release from the hydrogels was predominantly Fickian diffusion mediated and was released in its active form. The results suggested the potential use of the hydrogels as drug delivery matrices.

The current study reports the effect of regular Cannabis sativa (bhang) consumption on the autonomic nervous system (ANS) and the conduction pathway of the heart of the Indian paddy field workers. Twenty-four paddy field workers were selected for the study and electrocardiogram (ECG) signal was recorded. The physiological modulation in the ANS was analyzed in a non-invasive manner using heart rate variability (HRV) parameters. The results suggested a sympathetic dominance in the bhang users. ECG signal divulges information about the cardiac physiology and the conduction pathway of the heart. Time-domain and joint time-frequency domain analyses of ECG signal suggested alterations in the cardiac conduction pathway of bhang users. Artificial neural network based classification using the important predictors as categorical inputs resulted in an efficiency of > 80%.

Increasing evidence of peptide receptor overexpression in various cancer cells, warrant the development of receptor specific radiolabeled peptides for molecular imaging and therapy in nuclear medicine. Gastrin-releasing-peptide (GRP) receptor, are overexpressed in a variety of human cancer cells. The present study report the synthesis and biological evaluation of new bombesin (BBN) analogs, HYNIC-Asp-[Phe13]BBN(7–13)-NH-CH2-CH2-CH3:BA1, HYNIC-Pro-[Tyr13Met14]BBN(7–14)NH2:BA2 as prospective tumor imaging agent with compare to BBN(7–14)NH2:BS as standard. The pharmacophores were radiolabeled in high yields with 99mTc, characterized for their stability in serum and saline, cysteine/histidine and were found to be substantially stable. Internalization/externalization and receptor binding studies were assessed using MDA-MB-231 cells and showed high receptor binding-affinity and favourable internalization. Fluorescence studies revealed that BA1 changed the morphology of the cells and could localize in the nucleus more effectively than BA2/BS. Cell-viability studies displayed substantial antagonistic and nuclear-internalization effect of BA1. BA1 also exhibited antiproliferative effect on MDA-MB-231 cell by inducing apoptosis. In vivo behaviour of the radiopeptides was evaluated in GRP receptor positive tumor bearing mice. The 99mTc-BA1/99mTc-BA2 demonstrated rapid blood/urinary clearance through the renal pathway and comparatively more significant tumor uptake image and favourable tumor-to-non-target ratios provided by 99mTc-BA1. The specificity of the in vivo uptake was confirmed by co-injection with BS. Moreover, 99mTc-BA1 provided a much clearer tumor image in scintigraphic studies than others. Thus the combination of favourable in vitro and in vivo properties renders BA1 as more potential antagonist bombesin-peptide for targeting GRP-receptor positive tumor. These properties are encouraging to carry out further experiments for non-invasive receptor targeting potential diagnostinc and therapeutic agent for tumors.

Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a synthetic somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein loaded liposomes (DNL) were prepared and they were further decorated with the synthetic and stable analogue of somatostatin (SST-DNL). Fabricated liposomes were nano-size in range and biocompatible. SST-DNL displayed significantly better anti-tumor efficacy as compared to free Diacerein (DN) and DNL in breast cancer models. Enhanced apoptosis in breast cancer cells was detected in SST-DNL treated groups as monitored by cell cycle analysis and changes in expression level of apoptotic/anti-apoptotic proteins Bcl-2, Bax, cleaved Caspase 3 and PARP. SST-DNL more effectively inhibited the oncogenic IL-6/IL-6R/STAT3/MAPK/Akt signalling pathways as compared to DN or DNL in cancer cells. In addition, SST-DNL effectively suppressed angiogenesis and cancer cell invasion. In vivo tumor growth in a MDA-MB-231 mouse xenograft model was significantly suppressed following SST-DNL treatment. In xenograft model, immunohistochemistry of Ki-67 and CD-31 indicated that SST-DNL improved the anti-proliferative and anti-angiogenic impacts of Diacerein. In vivo pharmacokinetic studies in rats showed enhanced circulation time in the DNL or SST-DNL treated groups as compared to free DN. Considering all of these findings, we conclude that SST-DNL provides a novel strategy with better efficacy for breast cancer therapy.

Seven hexacoordinated cis-dioxidomolybdenum(VI) complexes [MoO2L1-7] (1-7) derived from various tetradentate diamino bis(phenolato) "salan" ligands, N,N'-dimethyl-N,N'-bis-(2-hydroxy-3-X-5-Y-6-Z-benzyl)-1,2-diaminoethane {(X=Br, Y=Me, Z=H (H2L1); X=Me, YCl, Z=H (H2L2); X=iPr, Y=Cl, Z=Me (H2L3)} and N,N'-bis-(2-hydroxy-3-X-5-Y-6-Z-benzyl)-1,2-diaminopropane {(X=Y=tBu, Z=H (H2L4); X=Y=Me, Z=H (H2L5); X=iPr, YCl, Z=Me (H2L6); X=Y=Br, Z=H (H2L7)} containing O-N donor atoms, have been isolated and structurally characterized. The formation of cis-dioxidomolybdenum(VI) complexes was confirmed by elemental analysis, IR, UV-vis and NMR spectroscopy, ESI-MS and cyclic voltammetry. X-ray crystallography showed the O2N2 donor set to define an octahedral geometry in each case. The complexes (1-7) were tested for their in vitro antiproliferative activity against HT-29 and HeLa cancer cell line. IC50 values of the complexes in HT-29 follow the order 6

The present study delineates the synthesis of novel composite films using polyvinyl alcohol and carboxymethyl tamarind gum. The microscopic study results confirmed the formation of composite matrices. FTIR spectroscopy suggested the occurrence of hydrogen-bonding amongst the components of the films. The extent of hydrogen bonding was composition-dependent which reached a critical higher limit at a particular composition. At the critical composition, the instantaneous and the intermediate polymer relaxation time were longer. All the films were found to be viscoelastic in nature. The melting endotherm was also highest for the composition described above. Ciprofloxacin loaded films showed excellent antimicrobial property against E. coli, suggesting that the drug was released in its active form. Cell proliferation study using human keratinocytes suggested better cell proliferation in the CMT containing films as compared to the control (PVA only) film. In gist, the developed films can be explored for skin tissue engineering and drug delivery applications.

The present study deals with the encapsulation of vegetable organogels in alginate microparticles (MPs). Mango butter (MB) and cocoa butter (CB) are natural organogels, which are being used in the preparation of pharmaceutical formulations. In addition to these, mustard oil (MO) was used as the control. The thermal stability of MB and CB can be enhanced by encapsulating them and can be used in oral drug-delivery formulations. Double emulsification method was followed for the preparation of MPs. By this method, spherical MPs were synthesized and the sphericity was confirmed by doing light microscopy and scanning electron microscopy. The size range of MPs was 107 ± 53 μm, 79 ± 43 μm, and 112 ± 78 μm for MPs encapsulating MO, MB, and CB, respectively. The melting endotherms of MPs with MB and CB were in exact match with the melting points of MB and CB. This confirmed the existence of MB and CB within the MPs. The encapsulation of the vegetable organogels altered the release pattern of the drug, metronidazole...

Peptides are attracting increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. We therefore synthesized new cyclic octapeptides conjugated with HYNIC by Fmoc solid-phase peptide synthesis. These were purified and analyzed by RP-HPLC, MALDI mass, (1)H NMR, (13)C NMR, HSQC, HMBC, COSY and IR spectroscopy. Conformational analysis of the peptides was performed by circular dichroism spectroscopy, in pure water and trifluoroethanol-water (1:1), revealed the presence of strong secondary structural features like β-sheet and random coils. Labeling was performed with (99m)Tc using Tricine and EDDA as coligands by SnCl(2) method to get products with excellent radiochemical purity99.5 %. Metabolic stability analysis did not show any evidence of breaking of the labeled compounds and formation of free (99m)Tc. Internalization studies were done and IC(50) values were determined in somatostatin receptor-expressing C6 glioma cell line and rat brain cortex membrane, and the results compared with HYNIC-TOC as standard. The IC(50) values of (99m)Tc-HYNIC-His(3)-Octreotate (21 ± 0.93 nM) and (99m)Tc-HYNIC-TOC (2.87 ± 0.41 nM) proved to be comparable. Biodistribution and image study on normal rat under gamma camera showed very high uptake in kidney and urine, indicating kidney as primary organ for metabolism and route of excretion. Biodistribution and image study on rats bearing C6 glioma tumor found high uptake in tumor (1.27 ± 0.15) and pancreas (1.71 ± 0.03). Using these findings, new derivatives can be prepared to develop (99m)Tc radiopharmaceuticals for imaging somatostatin receptor-positive tumors.

This Sodium temperature estimation in Intermediate Heat Exchanger is very significant for nuclear power generation in fast breeder test reactor (FBTR). Hence accurate evaluation of sodium temperature is a major concern both in case of offline and online operation of nuclear power plant (NPP). This paper addresses the training of artificial neural network model to precisely estimate the sodium temperature of Sodium-Sodium (Na-Na) Intermediate Heat exchanger and studying its behaviour at transient conditions. Severely unbalanced flow conditions in addition to steady state condition are investigated to generate sufficient number of dataset. Based on the in house data gathered from Quadratic Upstream Inter- polation for Convective Kinetics code (QUICK), a three layer neural network model is developed for training and subsequent validation. The back propagation (BP) algorithm is used for training the network. Further a model based on Radial Basis Function (RBF) neural network is developed and trained and the results are compared with standard back propagation algo- rithm. From the comparison studies, it is found that the network trained with RBF converges faster than BP network. Training and testing results show the successful modelling of plant dynamics of the reactor with improved accuracy. ANN can be an alternative to the conventional model as it predicts the physical parameters without much complex calculations as used in conventional model.

Wound pH strongly influences residence time and activity of various growth factors during wound healing. Hence, a pH-responsive sustained release growth factor delivery system could be beneficial for effective treatment of wound. In this context, an effort was made to evaluate the potential of a poly(N-isopropylacrylamide-co-acrylic acid) hydrogel as pH-sensitive sustained release system for wound-pH-dependent therapeutics delivery. The polymer was synthesized via radical copolymerization and influence of pH on lower critical solution temperature (LCST), microarchitechture and swelling of the hydrogel was evaluated. Results showed a pH-dependent variation in the physical properties of the hydrogel within the wound pH range. Fluorescence recovery after photobleaching (FRAP) analysis endorsed a pH dependent restricted diffusion of the BSA in the hydrogel. Later, release of bovine serum albumin (BSA), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) (each 5%, w/v) from the hydrogel within the range of wound pH (pH 6.7-7.9) were examined. Analysis showed non-Fickian release of therapeutics from the hydrogel with a significant variation in release rate and cumulative release with the increase in pH. Retention of the bioactivity of the released EGF was confirmed by studying murine dermal fibroblast cell proliferation in vitro. Finally, a growth factor (EGF or VEGF)-loaded hydrogel was applied on a murine excisional wound model and showed augmentation of wound healing in comparison to conventional sustained release growth factor therapy.

Collagens presently used in tissue engineering are primarily of bovine or porcine origin. However, a risk of a spongiform encephalopathy epidemic has limited the use of collagen from these sources. Keeping the aforementioned perspective in mind, we explored the possibility of using domestic goat available in the subcontinent as a potential source of collagen for tissue-engineering application. This article delineates the isolation, physico-chemical characterization, biocompatibility study and wound healing application of acid soluble caprine (goat) tendon collagen (GTC). Physico-chemical characterization of 1% acetic acid extracted GTC was done by SDS-PAGE, amino-acid composition analysis, FT-IR and CD spectroscopy. Results revealed that GTC was comprised of type-I collagen. Biocompatibility study showed that GTC augmented cell adhesion, cell cycle progression and proliferation. Immuno-cytochemical analysis in conjugation with traction force microscopy further confirmed a superior focal adhesion complex mediated cell-substrate interaction in GTC. Finally, in vivo study in mice model revealed that GTC has low immunogenicity and it augments healing process significantly. Throughout the study, calf skin collagen (CSC) was used as standard for comparative evaluation. In conclusion, it can be said that GTC may find its application as biomaterial in skin tissue engineering.

Background: Periodic evaluation of drug utilization pattern is necessary to promote rational drug use by. In orthopedics practice, the prescribing pattern needs to be regularly monitored since many of the drugs prescribed carry untoward adverse effects. In this backdrop, the present study was conducted to explore the prescribing pattern in orthopedics outpatient department (OPD) of a medical college in Eastern India. Methods: A cross-sectional study was conducted at a Tertiary Care Medical College in West Bengal. The prescriptions of all consecutive patients attending the orthopedics OPD for the first time (except post-surgical follow-up) were included in the study. Data analysis was done using descriptive statistical methods: frequencies, percentage, mean, and standard deviation. Results: A total of 837 prescriptions were analyzed with an average number of drugs per prescription being 2.57. Among the drugs, non-steroidal anti-inflammatory drugs were most commonly prescribed (64.14% [1383/2156]) followed by anti-ulcer drugs (13.58% [293/2156]), centrally acting muscle relaxants (21.4% [323/1516]), multivitamins and minerals (9.09% [196/2156]), and others (antibiotics, anti-gout drugs, etc.,) (5.12% [110/2156]). Drugs were prescribed in the generic name in 35.72% (770/2156) of prescriptions. A total of 71.56% (1543/2156) of drugs were prescribed from national essential medicine list. Antibiotics were prescribed in 53 encounters (53/2156 [2.46%]) and 93 prescriptions (4.38%) mentioned administration of injectables. The frequency of drug administration and the duration of treatment was mentioned in 87.81% (1893/2156) and 82% (1768/2156) of the prescriptions, respectively. Conclusion: The current piece of work pointed out certain lacunae in the prescribing practices of the orthopedicians of the institute as evidenced by low generic prescribing, inadequate information about the duration of therapy and frequency of administration in many prescriptions.

Present study reports synthesis and characterization of an enzymatically crosslinked injectable gel (iGel) suitable for cell based bone tissue engineering application. The gel comprises of carboxymethyl–chitosan (CMC)/gelatin/nano-hydroxyapatite (nHAp) susceptible to tyrosinase/p-cresol mediated in situ gelling at physiological temperature. Study revealed that a combination of tyrosinase (60U) and p-cresol (2 mM) as crosslinking agents yield rigid gels at physiological temperature when applied to CMC/gelatin within 35 min in presence or absence of nHAp. Rheological study in conjugation with FT-IR analysis showed that an increase in CMC concentration in the gel leads to higher degree of crosslinking and higher strength. Scanning electron microscopy showed that pore sizes of iGels increased with higher gelatin concentration. In vitro study of osteoblast cell proliferation and differentiation showed that, although all iGels are supportive towards the growth of primary osteoblast cells, GC1:1 supported cellular differentiation to the maximum. Application of iGels in mice revealed that stability of the in situ formed gels depends on the degree of crosslinking and CMC concentration. In conclusion, the iGels may be used in treating irregular small bone defects with minimal clinical invasion as well as for bone cell delivery.

In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T 2 contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T 2 relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.

Speech-controlled devices have been explored for potential applications in rehabilitation technology. These systems have shown great promises in improving the independence of the differently-abled persons by providing hands-free operation of the rehabilitative aids. The present study delineates the development of a speech-activated wireless control system for controlling rehabilitative devices. A robotic arm was used as the representative rehabilitative device. This technology can be extended to operate other rehabilitative aids (e.g., wheelchairs). The performance of the device was evaluated using ten volunteers. All the volunteers were able to accurately complete the desired movements of the robotic arm with relative ease. The developed device is simple and user-friendly.

Polylactic acid (PLA)-based composite films with four different loadings of nanoclay (2, 5, 10, and 15 wt %) were prepared using a solvent casting method and their crystalline morphology was investigated. The crystalline morphology was significantly different in the films depending on the clay content and its dispersion in the matrix. The clay platelets played the role of nucleating sites facilitating crystallization during solvent evaporation and this effect was most predominant in PLA 10. The % crystallinity and the crystallite size were determined by XRD analysis. The morphology was investigated with scanning electron microscopy (SEM) and by atomic force microscopy (AFM). A fibrillar pattern was evident in SEM micrographs, which were confirmed by AFM. The thermal properties were investigated with DSC and TGA. The glass transition temperature (Tg) increased from 51.9 to 55–57°C in all the nanocomposite samples. The melting peak temperature (168°C) remained unaltered in the nanocomposites, but the melting enthalpy varied depending on the PLA/clay interaction. The rate of degradation was controlled by the dispersion of clay platelets in the matrix and was very low in low clay-filled films. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Background Routes of transmission of hepatitis B virus (HBV)/HIV infections are similar and there is a significant rate of co-infection in patients. A study was recently carried out in NHS Fife, Scotland from February 2007 - February 2008 to estimate the prevalence of HBV/HIV co-infection, occult HBV infection and immunisation status against HBV in a cohort of patients with HIV attending the departments of infectious diseases and genitourinary medicine. Methods Case notes were reviewed retrospectively (n = 70). Details on patient demographics, risk category, nadir/current CD4 count, HIV viral load and vaccination history were analysed. HBV markers (HBsAg/anti-HBs/anti-HBc/HBV DNA) and alanine transaminase (ALT) levels were tested prospectively if these tests had not been carried out in the previous 12 months. Results and Conclusion Prevalence of HBV/HIV co-infection was 5.6% of which 2.8% of patients had occult infection and 22.9% had evidence of previous exposure. Although HBV is preventable by vaccination, only 24.2% of patients had been vaccinated against it. Improvements could therefore be made in the field of prevention with vaccination and monitoring the immune response in this cohort. Keywords Prevalence; Immunization status; Hepatitis B Virus; HIV

Cerebrovascular diseases (CVD) are dysfunctions of the brain, resulting from diseases of blood vessels supplying the brain. Atherosclerosis is one of the major underlying causes of CVD, in which inflammation plays a crucial role. One of the inflammatory mechanisms contributing to atherogenesis is the activation of monocytes and macrophages, which could be mediated by the bacterial endotoxin lipopolysaccharide (LPS) via its receptor CD14. The C260T (rs2569190) single-nucleotide polymorphism (SNP) in the promoter region of the CD14 gene was implicated in CVD. To assess the role of this SNP in CVD, a comprehensive meta-analysis of the available genetic data was conducted. All the case-control association studies evaluating the role of CD14 C260T in CVD were identified. Of these, 7 studies (comprising a total of 1488 patients and 1600 control subjects) were included in this meta-analysis. To measure the strength of genetic association for the gene variant, the odds ratios (ORs) were calculated using both fixed and random effects for comparisons of the alleles, the genotypes, and the dominant and recessive genotype models. The results showed there was no significant association between the T allele of C260T and the risk of CVD under the fixed effects model, OR = 0.99 (95% CI (0.89, 1.09)), P = 0.84; or the random effects model, OR = 0.99 (95% CI (0.88, 1.11)), P = 0.83. Similar results were obtained for the homozygotes and the dominant and recessive models. In conclusion, the results of this meta-analysis suggest the CD14 C260T polymorphism is not a risk factor for CVD. However, more studies in ethnically varied populations are needed to evaluate in a reliable manner the role of this SNP in CVD susceptibility.

In recent times, with technological advancements in medicine, materials science, and biology, the fi eld of tissue engineering has evolved. Tissue engineering deals with either the creation of tissues under ex vivo conditions or the regeneration of tissues under in vivo conditions. This entry has been designed to discuss the various approaches being taken to develop scaffolds from natural polymers. Attempts have also been made to discuss in brief the applications of the natural polymers in tissue engineering.

The current study delineates the development of novel gelatin-tamarind gum (TG)/ carboxymethyl tamarind gum (CMT)-based phase-separated films for probable skin tissue engineering applications. Polyethylene glycol was used as plasticizer. The films were characterized thoroughly using mechanical tester and impedance analyzer. Cell proliferation ability and drug release properties of the films were investigated. Mechanical studies indicated composition-dependent stress relaxation properties. Polysaccharide containing films supported better proliferation of human keratinocytes as compared to control. Drug loaded films showed good antimicrobial properties against E. coli. Analysis of the results indicated that the prepared films may be tried as matrices for skin tissue engineering.

The present study reports the in-depth analysis of the gelatin- carboxymethyl chitosan (CMC) hydrogels. The composite system formed phase-separated hydrogels, confirmed by scanning electron microscopy. The swelling of the CMC containing hydrogels was lower than the gelatin hydrogel. Macro-scale deformation study using a static mechanical tester indicated viscoelastic nature of the hydrogels. A decrease in the impedance of the hydrogels was observed with the increase in the CMC content. The drug release from the hydrogels was predominantly Fickian diffusion mediated and was released in its active form. The results suggested the potential use of the hydrogels as drug delivery matrices.

There is a persistent demand for an efficient drug delivery system, suitable for the delivery of both hydrophilic and lipophilic drugs. This study explores groundnut oil-based emulsion gels for the above-mentioned application. On the basis of stability, two representative gels OG5-80 (low oil content) and OG7-45 (high oil content) were studied further. Analysis of microarchitecture by ESEM and confocal microscopy, in conjugation with fluorescence recovery after photobleaching, confirmed the conversion of the dispersion phase from oil-continuous (OG7-45) to bicontinuous (OG5-80) with increasing water proportion. The gels were viscoelastic with unique stress relaxation properties. Passive and active (iontophoretic) release kinetics of the drugs showed differential release patterns. Mathematical modeling elucidated composition-dependent temporal variation in the drug release and stress relaxation patterns. In vitro cell viability study, cell cycle analysis, and immunocytochemistry divulged compatibility of the gels to human skin cells (keratinocytes). Drug-loaded gels were found active against B. subtilis and E. coli. Hence, groundnut oil-based emulsion gels can be an efficient and stable multimodal carrier system for the passive and the active delivery of both hydrophilic and lipophilic drugs.