Thermosensitive nasal in situ gelling systems of rufinamide formulated using modified tamarind seed xyloglucan for direct nose-to-brain delivery: design, physical characterization, and in vivo evaluation

Dalvi Avantika V.,Ravi Punna R.,Uppuluri Chandra T.,Mahajan Radhika R.,Katke Sumeet V.,Deshpande Vibha S. 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.2

Purpose Rufinamide is an anti-epileptic drug approved for use in children ≥ 4 years of age and in adults. It is marketed as Banzel in the USA. In 2015, Banzel received approval for use in pediatric patients (1–4 years of age) and the patent for which expires in 2023. It suffers from poor oral bioavailability, and hence, small amounts of the drug reach the brain. This has led to high and frequent dosage administration of rufinamide. This work aims to improve its brain bioavailability by formulating a nasal thermosensitive in situ gel using xyloglucan. Methods The formulation was optimized using rheometric analysis, texture analysis, in vitro, and in vivo studies. Pharmacokinetic studies in rats were carried out to assess direct nose to brain uptake for the optimized in situ gelling formulation of rufinamide and compared with intravenous bolus and aqueous nasal suspension of rufinamide. Finally, brain targeting indices % DTE, and % DTP were calculated. Results All the formulations showed gelation below 35 °C. The final formulation comprised 2.0% w/v xyloglucan, 0.01% v/v thiomersal (preservative), and rufinamide in suspended form. The %DTE values for the in-situ gel formulation and aqueous suspension were 1069.94 and 146.88, and the %DTP values were 90.65 and 31.91, respectively. Conclusion This work demonstrated the superiority of the nasal gel formulation over oral formulation of rufinamide. If translated to humans, this would definitely help patients suffering from epilepsy, especially pediatric population, in whose case, a high dose and frequent dosage administration via oral route is inconvenient.

Cytogenetic Profile of De Novo B lineage Acute Lymphoblastic Leukemia: Determination of Frequency, Distribution Pattern and Identification of Rare and Novel Chromosomal Aberrations in Indian Patients

Bhandari, Prerana,Ahmad, Firoz,Dalvi, Rupa,Koppaka, Neeraja,Kokate, Prajakta,Das, Bibhu Ranjan,Mandava, Swarna Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: Chromosomal aberrations identified in acute lymphoblastic leukemia (ALL) have an important role in disease diagnosis, prognosis and management. Information on karyotype and associated clinical parameters are essential to physicians for planning cancer control interventions in different geographical regions. Materials and Methods: In this study, we present the overall frequency and distribution patterns of chromosomal aberrations in both children and adult de novo B lineage ALL Indian patients using conventional cytogenetics, interphase FISH and multiplex RT-PCR. Results: Among the 215 subjects, cytogenetic results were achieved in 172 (80%) patients; normal karyotype represented 37.2% and abnormal 62.8% with a distribution as follows: 15.3% hypodiploidy; 10.3% hyperdiploidy; 15.8% t(9;22); 9.8% t(1;19); 3.7% t(12;21); 2.8% t(4;11); 2.8% complex karyotypes. Apart from these, we observed several novel, rare and common chromosomal rearrangements. Also, FISH studies using LSI extra-signal dual-color probes revealed additional structural or numerical changes. Conclusions: These results demonstrate cytogenetic heterogeneity of ALL and confirm that the incidence of chromosomal abnormalities varies considerably. To the best of our knowledge, this is one of the largest reported series of cytogenetic investigations in Indian B-lineage ALL cases. In addition, ongoing cytogenetic studies are warranted in larger groups of B-lineage ALL cases to identify newly acquired chromosomal abnormalities that may contribute to disease diagnosis and management.

Evaluating the efficacy of different curcumin polymorphs in transdermal drug delivery

Pandey Komal Upendra,Joshi Amita,Dalvi Sameer Vishvanath 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.1

Purpose Curcumin exists in three polymorphic forms: one monoclinic form and two orthorhombic forms. This work aims to investigate the efficacy of curcumin polymorphs in transdermal drug delivery by formulating curcumin polymorphs and their incorporation in polymeric films. Methods Monoclinic form, Form 1, was precipitated by liquid antisolvent technique from acetone solutions, whereas orthorhombic form, Form 2, was obtained by vacuum evaporation of solutions of curcumin in a mixed solvent of chloroform and hexane (60:40%v/v). The other orthorhombic form, Form 3, was precipitated from dimethylsulfoxide solutions. All three curcumin polymorphs were incorporated into polymeric films made of low molecular weight hydroxypropyl methyl cellulose (HPMC E5LV) along with different plasticizers, and permeation enhancers. Radical scavenging activity and cytotoxicity of curcumin polymorphs on human melanoma cell lines were evaluated. Water uptake, in-vitro release, and in-vitro permeation studies on HPMC films loaded with curcumin polymorph were carried out. Results Cytotoxicity studies on human melanoma cells (SK-MEL-28) showed that Form 2 results in the highest cell inhibition. Among all three curcumin polymorphs, the free radical scavenging activity of Form 3 was found to be the highest. HPMC films loaded with Form 3 exhibited higher water uptake and higher curcumin release profiles at pH of 5.5 (95.3% in 20 h) and pH 7.4 (79.8% in 20 h) as well as the highest in-vitro permeation compared to the other two curcumin forms. Conclusion Overall, orthorhombic curcumin polymorphs (i.e., Form 2 and Form 3) showed a higher propensity for transdermal drug delivery as compared to the monoclinic curcumin (Form 1).

Comparison of Vibrio spp. by employing proteomics

( Hyang Hee Yang ),( Rishikesh S. Dalvi ),( Seong Won Nho ),( Seong Bin Park ),( Ho Bin Jang ),( In Seok Cha ),( Mi Ae Ha ),( Young Rim Kim ),( Seong Joon Joh ),( Tae Sung Jung ) 한국수의공중보건학회 2008 예방수의학회지 Vol.32 No.3

The C2 Pedicle Width, Pars Length, and Laminar Thickness in Concurrent Ipsilateral Ponticulus Posticus and High-Riding Vertebral Artery: A Radiological Computed Tomography Scan-Based Study

Manish Kundanmal Kothari,Samir Surendranath Dalvie,Santosh Gupta,Agnivesh Tikoo,Deepak Kumar Singh 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.2

Study Design: Retrospective radiological study. Purpose: We aimed to determine the prevalence of ponticulus posticus (PP) and high-riding vertebral artery (HRVA) occurring simultaneously on the same side (PP+HRVA) and in cases of PP+HRVA, to assess C2 radio-anatomical measurements for C2 pars length, pedicle width, and laminar thickness. Overview of Literature: PP and HRVA predispose individuals to vertebral artery injuries during atlantoaxial fixation. In cases of PP+HRVA, the construct options thus become limited. Methods: Consecutive computed tomography scans (n=210) were reviewed for PP and HRVA (defined as an internal height of <2 mm and an isthmus height of <5 mm). In scans with PP+HRVA, we measured the ipsilateral pedicle width, pars length, and laminar thickness and compared them with controls (those without PP or HRVA). Results: PP was present in 14.76% and HRVA in 20% of scans. Of the 420 sides in 210 scans, PP+HRVA was present on 13 sides (seven right and six left). In scans with PP+HRVA, the C2 pars length was shorter compared with controls (13.69 mm in PP+HRVA vs. 20.65 mm in controls, p<0.001). The mean C2 pedicle width was 2.53 mm in scans with PP+HRVA vs. 5.83 mm in controls (p<0.001). The mean laminar thickness was 4.92 and 5.48 mm in scans with PP+HRVA and controls, respectively (p=0.209). Conclusions: The prevalence of PP+HRVA was approximately 3% in the present study. Our data suggest that, in such situations, C2 pedicle width and pars length create important safety limitations for a proposed screw, whereas the translaminar thickness appears safe for a proposed screw.

A Radiological Study of the Association of Facet Joint Tropism and Facet Angulation With Degenerative Spondylolisthesis

Ravi Ranjan Rai,Yash Shah,Siddharth Shah,Nigil Sadanandan Palliyil,Samir Dalvie 대한척추신경외과학회 2019 Neurospine Vol.16 No.4

Objective: To study the association of facet joint angulation and joint tropism with degenerative spondylolisthesis (DS) through a comparison with a matched control group. Methods: This radiographic study was carried out in 2 groups of 45 patients each. Group A contained patients with single-level DS, while group B (control) contained non-DS patients with similar age and degeneration who underwent surgery for disc prolapse or lumbar stenosis. DS was diagnosed based on translation of ≥3 mm on standing lateral radiography. Axial magnetic resonance imaging from L3 to S1 was utilized to assess the angulation of facet joints in relation to the coronal plane; a difference of ≥8° was considered to indicate tropism. Results: Among 45 patients with DS, 15 were males and 30 females. Their mean age was 62.2 years. Facet tropism was identified in 20 of 45 patients at the level of DS, 12 patients at a level proximal to DS, and 15 patients at a level distal to DS. Facet tropism was found in 7 of the 45 patients in group B. At L3–4, facet tropism was observed in 13 patients (28.88%) in group A and 2 (4.44%) in group B. At L4–5, tropism was observed in 19 patients (42.22%) in group A and 5 (11.11%) in group B. At L5–S1, tropism was seen in 17 patients (37.77%) in group A and 2 (4.44%) in group B. Group A showed a significantly higher prevalence of multilevel facet tropism and tropism at levels adjacent to the DS level. A higher average angulation of facet joints was observed in the DS group, but the difference was not statistically significant at all levels. Conclusion: The present study documented a statistically significant relationship between facet tropism and DS. A higher prevalence of facet tropism was also found in DS patients at non-DS levels, which is a novel observation. This finding supports the argument that facet tropism is a pre-existing morphological variation contributing to the development of DS, not a result of secondary remodelling.

Predictions of thermodynamic properties of pure fluids, refrigerants, and binary mixtures using modified Peng-Robinson equation of state

Pradnya Nirmala Prabhakar Ghoderao,Mohan Narayan,Vishwanath Haily Dalvi,변헌수 한국화학공학회 2022 Korean Journal of Chemical Engineering Vol.39 No.12

The Peng-Robinson (PR) EOS is a very successful two-parameter equation of state to estimate thermodynamicproperties of pure compounds as well as mixtures. The PR EOS has been modified and revised several ways toimprove estimates, and the most popular modification is for the attractive term through alpha function and temperaturedependent covolume parameter in the repulsive term. However, the unphysical, i.e., negative values of temperaturedependent co volume parameter at high temperature lead to undesirable results. We have addressed this issue inthe present work by incorporating a temperature dependent covolume parameter and yet physically consistent over alarge range of temperature. In the present work, the Modified-Peng-Robinson 2 (MPR2) equation of state is presentedby modifying the alpha function in attractive term and temperature dependent co-volume parameter in repulsive termof the PR EOS. The accuracy of MPR2 EOS is demonstrated by comparing results with the PR, HKM1, and MPR1equations of state. The thermodynamic properties, namely saturated vapor pressure and liquid density, enthalpy ofvaporization, compressed liquid densities in sub and supercritical region, heat capacities (isobaric and isochoric), andsound velocity of pure compounds, are predicted by MPR2 EOS which agrees very well with the experimental data. We have further studied 24 refrigerant properties like vapor and liquid densities. The work has also been extended tostudy the phase behavior of 26 binary mixtures using van der Waals single fluid mixing rules.

Seasonal variation and comparative analysis of non-specific humoral immune substances in the skin mucus of olive flounder (Paralichthys olivaceus)

Jung, T.S.,del Castillo, C.S.,Javaregowda, P.K.,Dalvi, R.S.,Nho, S.W.,Park, S.B.,Jang, H.B.,Cha, I.S.,Sung, H.W.,Hikima, J.i.,Aoki, T. Pergamon Press ; Elsevier Science Ltd ; Pergamon 2012 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.38 No.2

The epidermal secretion of fish contains various non-specific immune substances that act as the first line of defense against invading pathogens. The present study investigated the level of mucosal antibodies, the activities of hemagglutinin and protease, and other enzymes in the skin mucus of farm reared olive flounder (Paralichthys olivaceus) for 1year, in order to gain an insight into the relationship between these mucosal immune substances and their seasonal variation. These levels varied significantly during different months of sample collection. The present study showed a positive correlation between water temperature and the level of mucosal antibodies, and an inverse relationship between the level of mucosal antibodies and the activity of mucosal hemagglutinin and protease, but no relationship between lysozyme activity and other innate immune substances. This relationship is thought to be a compensatory response in olive flounder to protect itself against pathogenic microorganisms which are inherently present in the aquatic environment.

Predation behavior of Podisus nigrispinus on Spodoptera eridania

José Romário de Carvalho,Dirceu Pratissoli,Luis Moreira de Araujo Junior,Alixelhe Pacheco Damascena,Anderson Mathias Holtz,Leandro Pin Dalvi,Ulysses Rodrigues Vianna 한국응용곤충학회 2020 Journal of Asia-Pacific Entomology Vol.23 No.4

The behavior and effective predation time can affect the prey death in pest biological control programs. This work studied the Podisus nigrispinus (Dallas, 1851) (Heteroptera: Pentatomidae) behavior on Spodoptera eridania (Cramer, 1782) (Lepidoptera: Noctuidae) caterpillars, and its implications in case of prey escape. The preference bioassay (B1) aimed to verify the caterpillars body region (anterior: head and thorax; median and posterior) preferred by the predator and its implication in prey mortality. The predation duration bioassay considered the following effective predation times: 1, 2, 4, 8, 16, 32, 64 and 128 min; the caterpillars were removed after each predation time, to simulate prey escape, and the dead were counted until the seventh day. This experiment was performed in two ways: with randomly selected and not repeated predators (B2); and with the same predators in successive times (B3). The predator preferred to attack the caterpillars anterior region. The caterpillars mortality increased with increasing effective predation time. The mortality was 90% after 64 min under B2. This value was estimated for 16 min under B3. The P. nigrispinus prefers to attack the caterpillars anterior region and mortality of S. eridania caterpillars was favored in predators that have suffered predation interruption.

Comparison of antigenic proteins from <i>Lactococcus garvieae</i> KG (−) and KG (+) strains that are recognized by olive flounder (<i>Paralichthys olivaceus</i>) antibodies

Shin, Gee-Wook,Nho, Seong-Won,Park, Seong-Bin,Jang, Ho-Bin,Cha, In-Seok,Ha, Mi-Ae,Kim, Young-Rim,Dalvi, Rishikesh S.,Joh, Seong-Joon,Jung, Tae-Sung Elsevier 2009 Veterinary microbiology Vol.139 No.1

<P><B>Abstract</B></P><P><I>Lactococcus garvieae</I> is an important etiological agent of lactococcosis in various fish species including olive flounder (<I>Paralichthys olivaceus</I>). In this study, proteomic and immunoproteomic analyses were employed to compare the antigenic profiles of strains KG9408, MS93003, and NSS9310 strains of <I>L. garvieae</I>. Proteomic analysis using two-dimensional gel electrophoresis (2-DE) revealed differences in five protein spots among the different <I>L. garvieae</I> strains. In immunoproteomic analysis, there was a significant difference in the 2-DE immunoblot profiles of the <I>L. garvieae</I> strains using sera collected from fish surviving infection with either <I>L. garvieae</I> strains KG9408 or NSS9310. These sera reacted with 8 and 7 unique antigenic protein spots, respectively. Heat shock protein (HSP) 70 and DNA-directed RNA polymerase were among the specific antigens recognized by the anti-NSS9310 serum. In addition, the anti-NSS9310 and anti-KG9408 olive flounder sera reacted with 25 common antigenic protein spots of all the <I>L. garvieae</I> strains, which included elongation factor (EF)-Tu, arginine deiminase (AD), inosine-5′-monophosphate dehydrogenase (IMPD), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphomannomutase (PMM), <SMALL>L</SMALL>-lactate dehydrogenase (<SMALL>L</SMALL>-LDH), 6-phosphofructokinase and UDP-galactose 4-epimerase (UDP-galactose). Based on the present results, the 8 antigens recognized by the anti-KG9408 serum and the 25 common antigens recognized by both sera may serve as potential markers for developing an effective vaccine against this bacterium.</P>