Evaluation of the Liquisolid Compacts Using Response Surface Methodology

Liquisolid Compacts technique has potential to develop sustained release formulations. It involves conversion of liquid drug (either solution or suspension) in non-volatile solvent into free-flowing, non adherent, dry looking and readily compressible powder. In the present work, an attempt was made to develop such formulation of Diltiazem HCl and evaluation using Response surface methodology. Liquisolid compacts were prepared by dissolving Diltiazem HCl in Polyethylene Glycol 400. Then a binary mixture of carrier-coating material, Avicel and Aerosil, was added to liquid medication under continuous mixing in mortar. The HPMC K4M was used as adjuvant for sustaining the drug release.  The pre-compression studies for all the formulations were also carried out. The Liquisolid compacts were evaluated in-vitro dissolution studies. The experimental data was evaluated using Design Expert Software. The % Drug Concentration, ratio of Carrier to Coating material and amount of HPMC K4M are taken as three factors. Response Surface methodology was used to study the influence of the each factor on the response. The present investigation showed that Polyethylene Glycol 400 has important role in release retardation of drug in Liquisolid compacts. The reduction in Tg can be reason for same. The Response surface methodology showed that all the factors were significantly affect the release at 16 hrs.

Role of locking compression plate in management of metaphyseal fractures in osteoporotic bones: an experimental study from rural Maharashtra

Background: Osteoporosis is multi factorial disease, which is caused by complex interaction between genetic and environmental factors that influence bone turnover, bone mass, skeletal geometry and risk factors. Distal femur fracture needs aggressive management in terms of open reduction and internal fixation with locking compression plate and early mobilization. Objectives were to study the role of locking compression plate in the management of osteoporotic metaphyseal fractures.Methods: Present study is a prospective study comprising of 50 patients who sustained various fractures in different bones of body due to osteoporosis and were treated using locking compression plate (LCP). All patients were evaluated for effectiveness of LCP.Results: In present series majority of patients (44%) fall in age group of 61-70 years having senile osteoporosis, followed by 12 (24%) from 51-60 years age group. Majority of the cases involved were distal femur fractures (50%). 15 i.e. 30% cases were fracture of proximal tibia and 20% were fracture of proximal humerus. 96% had osteoporosis. C1 type of fracture was commonly seen in 6 (12%) patients. The mean constant score at one month was 58 and at the end of one year it was 80. The mean oxford score at one month was 28 and at the end of one year it was 38.Conclusions: Locking compression plate is an ideal implant for fixation in metaphyseal osteoporotic bones when used methodically

Evaluation of the Liquisolid Compacts Using Response Surface Methodology

Liquisolid Compacts technique has potential to develop sustained release formulations. It involves conversion of liquid drug (either solution or suspension) in non-volatile solvent into free-flowing, non adherent, dry looking and readily compressible powder. In the present work, an attempt was made to develop such formulation of Diltiazem HCl and evaluation using Response surface methodology. Liquisolid compacts were prepared by dissolving Diltiazem HCl in Polyethylene Glycol 400. Then a binary mixture of carrier-coating material, Avicel and Aerosil, was added to liquid medication under continuous mixing in mortar. The HPMC K4M was used as adjuvant for sustaining the drug release.  The pre-compression studies for all the formulations were also carried out. The Liquisolid compacts were evaluated in-vitro dissolution studies. The experimental data was evaluated using Design Expert Software. The % Drug Concentration, ratio of Carrier to Coating material and amount of HPMC K4M are taken as three factors. Response Surface methodology was used to study the influence of the each factor on the response. The present investigation showed that Polyethylene Glycol 400 has important role in release retardation of drug in Liquisolid compacts. The reduction in Tg can be reason for same. The Response surface methodology showed that all the factors were significantly affect the release at 16 hrs.

Ultrafast Dynamics of Gold Nanorods: Tuning between Photo-Bleaching and Photo-Induced Absorption

We report ultrafast electron dynamics in gold nanorods investigated using 80 fs laser pulses centered at 1.57 eV. Five types of nanorod colloidal suspensions in water having their longitudinal surface plasmon peak (ELSP) on either side of the laser photon energy (EL) have been studied. For ELSP>EL, photo-induced absorption with single decay time constant is observed. On the other hand, for ELSP<EL, photo-bleaching is observed having biexponential decay dynamics; the faster one between 1-3 ps and slower one between 7ps to 22ps both of them increasing almost linearly with the difference |EL-ELSP|. These time constants increase linearly with the pump intensity. Simulations have been carried out to understand the interplay between photo-bleaching and photoinduced absorption.Comment: 4 pages, 4 figures, To appear in International Journal of Nanoscience, 201

Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility

Duffy antigen receptor for chemokines (DARC) expressed on red blood cells (RBCs) influences plasma levels of HIV-1-suppressive and proinflammatory chemokines such as CCL5/RANTES. DARC is also the RBC receptor for Plasmodium vivax. Africans with DARC -46C/C genotype, which confers a DARC negative phenotype, are resistant to vivax malaria. Here, we show that HIV-1 attaches to RBCs via DARC, effecting trans-infection of target cells. In African Americans, DARC -46C/C is associated with 40% increase in the odds of acquiring HIV-1. If extrapolated to Africans, ~11% of the HIV-1 burden in Africa may be linked to this genotype. After infection occurs, however, DARC-negative RBC status is associated with slower disease progression. Furthermore, the disease-accelerating effect of a previously described CCL5 polymorphism is evident only in DARC-expressing and not in DARC-negative HIV-infected individuals. Thus, DARC influences HIV/AIDS susceptibility by mediating trans-infection of HIV-1 and by affecting both chemokine-HIV interactions and chemokine-driven inflammation

Duffy-Null–Associated Low Neutrophil Counts Influence HIV-1 Susceptibility in High-Risk South African Black Women.

Background. The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)–1 infection among Africans is unknown. Methods. The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity. Results. Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of C) was significantly associated with neutrophil counts (P = 7.9 x10-11). DARC -46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm3. The risk of acquiring HIV infection was ~3-fold greater in those with the trait of Duffy-null–associated low neutrophil counts, compared with all other study participants. Conclusions. Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null–associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa

CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1–infected individuals

The basis for the extensive variability seen in the reconstitution of CD4+ T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4+ T cells/mm3. The CCL3L1-CCR5 genotypes favoring CD4+ T cell recovery are similar to those that blunted CD4+ T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4+ cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution

Role of CCL3L1-CCR5 Genotypes in the Epidemic Spread of HIV-1 and Evaluation of Vaccine Efficacy

Polymorphisms in CCR5, the major coreceptor for HIV, and CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine, are determinants of HIV-AIDS susceptibility. Here, we mathematically modeled the potential impact of these genetic factors on the epidemic spread of HIV, as well as on its prevention.Ro, the basic reproductive number, is a fundamental concept in explaining the emergence and persistence of epidemics. By modeling sexual transmission among HIV+/HIV- partner pairs, we find that Ro estimates, and concordantly, the temporal and spatial patterns of HIV outgrowth are highly dependent on the infecting partners' CCL3L1-CCR5 genotype. Ro was least and highest when the infected partner possessed protective and detrimental CCL3L1-CCR5 genotypes, respectively. The modeling data indicate that in populations such as Pygmies with a high CCL3L1 gene dose and protective CCR5 genotypes, the spread of HIV might be minimal. Additionally, Pc, the critical vaccination proportion, an estimate of the fraction of the population that must be vaccinated successfully to eradicate an epidemic was <1 only when the infected partner had a protective CCL3L1-CCR5 genotype. Since in practice Pc cannot be >1, to prevent epidemic spread, population groups defined by specific CCL3L1-CCR5 genotypes might require repeated vaccination, or as our models suggest, a vaccine with an efficacy of >70%. Further, failure to account for CCL3L1-CCR5-based genetic risk might confound estimates of vaccine efficacy. For example, in a modeled trial of 500 subjects, misallocation of CCL3L1-CCR5 genotype of only 25 (5%) subjects between placebo and vaccine arms results in a relative error of approximately 12% from the true vaccine efficacy.CCL3L1-CCR5 genotypes may impact on the dynamics of the HIV epidemic and, consequently, the observed heterogeneous global distribution of HIV infection. As Ro is lowest when the infecting partner has beneficial CCL3L1-CCR5 genotypes, we infer that therapeutic vaccines directed towards reducing the infectivity of the host may play a role in halting epidemic spread. Further, CCL3L1-CCR5 genotype may provide critical guidance for optimizing the design and evaluation of HIV-1 vaccine trials and prevention programs

Water Extract from the Leaves of Withania somnifera Protect RA Differentiated C6 and IMR-32 Cells against Glutamate-Induced Excitotoxicity

Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty

Kilonova Luminosity Function Constraints Based on Zwicky Transient Facility Searches for 13 Neutron Star Merger Triggers during O3

We present a systematic search for optical counterparts to 13 gravitational wave (GW) triggers involving at least one neutron star during LIGO/Virgo's third observing run (O3). We searched binary neutron star (BNS) and neutron star black hole (NSBH) merger localizations with the Zwicky Transient Facility (ZTF) and undertook follow-up with the Global Relay of Observatories Watching Transients Happen (GROWTH) collaboration. The GW triggers had a median localization area of 4480 deg², a median distance of 267 Mpc, and false-alarm rates ranging from 1.5 to 10⁻²⁵ yr⁻¹. The ZTF coverage in the g and r bands had a median enclosed probability of 39%, median depth of 20.8 mag, and median time lag between merger and the start of observations of 1.5 hr. The O3 follow-up by the GROWTH team comprised 340 UltraViolet/Optical/InfraRed (UVOIR) photometric points, 64 OIR spectra, and three radio images using 17 different telescopes. We find no promising kilonovae (radioactivity-powered counterparts), and we show how to convert the upper limits to constrain the underlying kilonova luminosity function. Initially, we assume that all GW triggers are bona fide astrophysical events regardless of false-alarm rate and that kilonovae accompanying BNS and NSBH mergers are drawn from a common population; later, we relax these assumptions. Assuming that all kilonovae are at least as luminous as the discovery magnitude of GW170817 (−16.1 mag), we calculate that our joint probability of detecting zero kilonovae is only 4.2%. If we assume that all kilonovae are brighter than −16.6 mag (the extrapolated peak magnitude of GW170817) and fade at a rate of 1 mag day⁻¹ (similar to GW170817), the joint probability of zero detections is 7%. If we separate the NSBH and BNS populations based on the online classifications, the joint probability of zero detections, assuming all kilonovae are brighter than −16.6 mag, is 9.7% for NSBH and 7.9% for BNS mergers. Moreover, no more than 10⁻⁴, or φ > 30° to be consistent with our limits. We look forward to searches in the fourth GW observing run; even 17 neutron star mergers with only 50% coverage to a depth of −16 mag would constrain the maximum fraction of bright kilonovae to <25%