Synthesis and Immunological Activity of Novel Oligo(ethylene glycol) Analogues of α-Galactosylceramide.

CD1d-arbitrated activation of i-NKT cells by α-galactosylceramide results in the effective secretion of Th1 and Th2 cytokines, with adjuvanticity skewed toward Th2 immunity. However, the polarization of immune response could be achieved by suitable modification of the glycolipid structure. In the current study, novel glycolipids with an amphiphilic oligo ethylene glycol lipid moiety bearing the benzyloxy group at the terminus on the acyl arm of sphingosine, exhibited CD1d ligand binding as quantified by IL-2 cytokine production. When immunized with quadrivalent split influenza virus in BALB/c mice, the novel ceramide analogues with a longer oligo (ethylene glycol) chain length induced significant levels of antibody (IgG) with Th1-polarized immune response.

Repeatability and reproducibility study of radiomic features on a phantom and human cohort.

The repeatability and reproducibility of radiomic features extracted from CT scans need to be investigated to evaluate the temporal stability of imaging features with respect to a controlled scenario (test-retest), as well as their dependence on acquisition parameters such as slice thickness, or tube current. Only robust and stable features should be used in prognostication/prediction models to improve generalizability across multiple institutions. In this study, we investigated the repeatability and reproducibility of radiomic features with respect to three different scanners, variable slice thickness, tube current, and use of intravenous (IV) contrast medium, combining phantom studies and human subjects with non-small cell lung cancer. In all, half of the radiomic features showed good repeatability (ICC > 0.9) independent of scanner model. Within acquisition protocols, changes in slice thickness was associated with poorer reproducibility compared to the use of IV contrast. Broad feature classes exhibit different behaviors, with only few features appearing to be the most stable. 108 features presented both good repeatability and reproducibility in all the experiments, most of them being wavelet and Laplacian of Gaussian features.

Environmental effects on the oxygen consumption rate in juvenile Epinephelus fuscoguttatus (Forsskal, 1775).

This study was designed to optimize the culture conditions of juvenile Epinephelus fuscoguttatus (Forsskål, 1775) under laboratory conditions. To this effect, the rate of oxygen consumption was monitored as an index of stress under different temperature, salinity, pH, photoperiod, and urea concentrations. The result obtained after 12 h of exposure suggests the preference of the juvenile E. fuscoguttatus to a temperature range of 15-25 °C and salinity of 30 ppt. Based on this study, temperature was found to be the most lethal as 100% mortality was observed after 6 h in fish exposure to temperatures above the optimal (≥ 30 °C). However, the oxygen consumption rate was similar under the different pH, photoperiod, and urea concentration tested. It was concluded that water temperature was most critical in terms of respiration physiology of the juvenile E. fuscoguttatus given the range and levels of environmental factors tested in this study.

Rare Case of Iliopsoas Abscess Secondary to Mucinous Adenocarcinoma of the Colon: A Case Report.

INTRODUCTION: Iliopsoas abscess (IPA) has varied clinical symptomatology and various clinical disorders may mimic it. Tuberculosis of spine is the most common source of secondary IPA in the developing countries. However, IPA may be rarely caused by colon cancer which is the most common gastrointestinal malignancy. A mixed culture gives an indication of gastrointestinal or genitourinary etiology. We present here, a rare case of an 86-year-old patient with IPA secondary to adenocarcinoma of colon. CASE REPORT: An 86-year-old female presented with pain in the right thigh in February 2014. Computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen confirmed the clinical suspicion of right IPA which was drained surgically. Intraoperatively, mucinous material was noted, emerging from a small opening in a rounded structure located lateral to the psoas muscle, which could not be identified. On post-operative day 2, the right flank swelling recurred. Culture reports showed a polymicrobial infection with viridans group Streptococci and Pseudomonas aeruginosa. The abscess was re-explored and biopsy of the opening was taken. Histopathology of the tissue sample revealed metastatic cells of a mucin-secreting adenocarcinoma that had infiltrated the psoas muscle with a secondary pyogenic abscess. On reviewing the CT scan, there was a suspicion that the abscess was communicating with a tumor in the colon. No further active intervention was done for the tumor in view of advanced age and stage of tumor. The patient had significant pain relief and was able to resume walking. The infection resolved with 6 weeks of oral linezolid and ciprofloxacin. The patient died 8 months later secondary to metastasis. CONCLUSION: Although the diagnosis of IPA does not pose problems, diagnosing secondary IPA requires a high index of clinical suspicion. A Gram-negative culture must raise the suspicion of gastrointestinal or genitourinary pathology. Colon carcinoma, although extremely rare, can lead to secondary IPA. CT and MRI though extremely useful, may not pick up the pathology and a definitive diagnosis of colon neoplasia perforating into the psoas muscle may be evident only intraoperatively. Atypical presentation may delay the diagnosis of colon cancer and subsequently result in higher morbidity and mortality.

Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues.

Replacement of the amide moiety in the structure of α-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl α-GalCer analogues are reported. The novel α-GalCer analogues activate invariant natural killer T (iNKT) cells via CD1d mediated presentation, which was confirmed by in vitro tests performed on iNKT hybridomas incubated with CD1d proteins. When tested on isolated murine splenocytes, the T1204B and T1206B compounds stimulated higher levels of both IFN-γ and IL-4 cytokine expression in vitro compared to that of α-GalCer.

Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A review.

Caesalpinia sappan L. (CS) is a plant of Leguminosae family, commonly known as Brazil or Sappan wood. CS is distributed in Southeast Asia and its dried heartwood has been used as traditional ingredient of food or beverages and has a wide variety of medicinal properties. Higher extraction yield of CS wood was achieved with 95% ethanol for 2 h. Chemical constituent's investigation of sappan wood resulted in the isolation of various structural types of phenolic components including one xanthone, one coumarin, three chalcones, two flavones three homoisoflavonoids and brazilin. Brazilin [(6a S-cis)-7, 11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10(6H)- tetrol], a major and active compound found in CS heartwood. Most of the folkloric uses of brazilin were validated by the scientific studies such as antioxidant, antibacterial, anti-inflammatory, anti-photoaging, hypoglycemic, vasorelaxant, hepatoprotective and anti-acne activity. CS heartwood extract is safe and did not produce any acute or subacute toxicity in both male and female rats. Brazilin is the safe natural compound having potential to develop as a medicinal compound with application in food, beverage, cosmetics and pharmaceutical industries to screen its clinical use in modern medicine. The information gained could provide the important and potential approach for pharmaceutical researcher to implicate the knowledge of brazilin in the formulation of new drug and to reveal therapeutic and gaps requiring future research opportunities. More studies are needed to evaluate the potential application of brazilin as preservative and coloring agent in food processing industries.

Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A review

Caesalpinia sappan L. (CS) is a plant of Leguminosae family, commonly known as Brazil or Sappan wood. CS is distributed in Southeast Asia and its dried heartwood has been used as traditional ingredient of food or beverages and has a wide variety of medicinal properties. Higher extraction yield of CS wood was achieved with 95% ethanol for 2h. Chemical constituent's investigation of sappan wood resulted in the isolation of various structural types of phenolic components including one xanthone, one coumarin, three chalcones, two flavones three homoisoflavonoids and brazilin. Brazilin [(6a S-cis)-7, 11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10(6H)- tetrol], a major and active compound found in CS heartwood. Most of the folkloric uses of brazilin were validated by the scientific studies such as antioxidant, antibacterial, anti-inflammatory, anti-photoaging, hypoglycemic, vasorelaxant, hepatoprotective and anti-acne activity. CS heartwood extract is safe and did not produce any acute or subacute toxicity in both male and female rats. Brazilin is the safe natural compound having potential to develop as a medicinal compound with application in food, beverage, cosmetics and pharmaceutical industries to screen its clinical use in modern medicine. The information gained could provide the important and potential approach for pharmaceutical researcher to implicate the knowledge of brazilin in the formulation of new drug and to reveal therapeutic and gaps requiring future research opportunities. More studies are needed to evaluate the potential application of brazilin as preservative and coloring agent in food processing industries.

Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A review

Caesalpinia sappan L. (CS) is a plant of Leguminosae family, commonly known as Brazil or Sappan wood. CS is distributed in Southeast Asia and its dried heartwood has been used as traditional ingredient of food or beverages and has a wide variety of medicinal properties. Higher extraction yield of CS wood was achieved with 95% ethanol for 2 h. Chemical constituent's investigation of sappan wood resulted in the isolation of various structural types of phenolic components including one xanthone, one coumarin, three chalcones, two flavones three homoisoflavonoids and brazilin. Brazilin [(6a S-cis)-7, 11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10(6H)- tetrol], a major and active compound found in CS heartwood. Most of the folkloric uses of brazilin were validated by the scientific studies such as antioxidant, antibacterial, anti-inflammatory, anti-photoaging, hypoglycemic, vasorelaxant, hepatoprotective and anti-acne activity. CS heartwood extract is safe and did not produce any acute or subacute toxicity in both male and female rats. Brazilin is the safe natural compound having potential to develop as a medicinal compound with application in food, beverage, cosmetics and pharmaceutical industries to screen its clinical use in modern medicine. The information gained could provide the important and potential approach for pharmaceutical researcher to implicate the knowledge of brazilin in the formulation of new drug and to reveal therapeutic and gaps requiring future research opportunities. More studies are needed to evaluate the potential application of brazilin as preservative and coloring agent in food processing industries.

Outcome of surgical management of developmental dysplasia of hip in children between 18 and 24 months.

BACKGROUND: Developmental dysplasia of hip (DDH) is a common condition presenting to a pediatric orthopedic surgeon. There is a consensus on the surgical treatment of children with ages ranged from 18 to 24 months where majority agree on open reduction and hip spica. Open reduction was done with an additional pelvic procedure wherever required to get better results and prevent residual acetabular dysplasia (RAD) and early osteoarthritis. MATERIALS AND METHODS: 35 children with unilateral DDH were operated between 2002 and 2007 at our institute. Open reduction was performed in all using the standard anterior approach and peroperative test for hip stability was done. Nine children got an additional pelvic procedure in the form of Dega acetabuloplasty. All were followed up for a minimal period of 2 years (range 2-7 years). RESULTS: No hip got redislocated. At the end of 18 months, there were seven cases of RAD with acetabular index (AI) of 35° and above. These were all from the group where open reduction alone was done. CONCLUSION: We feel that a preoperative AI of >40° and a per-operative safe-zone <20° increases the need for supplementary pelvic osteotomy in age group of 18 to 24 months because in such cases, the remodeling capacity of the acetabulum is unable to overcome the dysplasia and to form a relatively normal acetabulum.

Implementation and evaluation of adverse drug reaction monitoring system in a tertiary care teaching hospital in Mumbai, India.

Adverse drug reactions (ADR) are a significant cause of morbidity and mortality, often identified only post-marketingly. Improvement in current ADR reporting, including utility of underused or innovative methods, is crucial to improve patient safety and public health. Hospital-based monitoring is one of the methods used to collect data about drug prescriptions and adverse events. The aims of this study were to identify the most frequent ADRs recognized by the attending physicians, study their nature, and to target these ADRs in order to take future preventive measures. A prospective study was conducted over a 7-month period in an internal medicine department using stimulated spontaneous reporting for identifying ADRs. Out of the 254 admissions, 32 ADRs in 37 patients (14.56%) were validated from the total of 36 suspected ADRs in 41 patients. Female predominance was noted over males in case of ADRs. Fifty percent of total ADRs occurred due to multiple drug therapy. Dermatological ADRs were found to be the most frequent (68.75%), followed by respiratory, central nervous system and gastrointestinal ADRs. The drugs most frequently involved were antibiotics, anti-tubercular agents, antigout agents, and NSAIDs. The most commonly reported reactions were itching and rashes. Out of the 32 reported ADRs, 50% of the reactions were probable, 46.87% of the reactions were possible and 3.12% of the reactions were definite. The severity assessment done by using the Hartwig and Seigel scale indicated that the majority of ADRs were 'Mild' followed by 'Moderate' and 'Severe' reactions, respectively. Out of all, 75% of ADRs were recovered. The most potent management of ADRs was found to be drug withdrawal. Our study indicated that hospital based monitoring was a good method to detect links between drug exposure and adverse drug reactions. Adequate training regarding pharmacology and optimization of drug therapy might be helpful to reduce ADR morbidity and mortality.

Development of an ex vivo model for pharmacological experimentation on isolated tissue preparation.

Pharmacology as a subject depends largely on experiments conducted in laboratory animals. Experimental animals like rat, guinea pig, rabbit, etc. are used for the biological assay. For the teaching purposes to use isolated strip preparations from various organs, the laboratory animal species has to be sacrificed just for a piece of tissue. The present study was aimed to develop ex vivo model for pharmacological experimentation, which will mimic the actual laboratory condition without sacrificing the experimental animals. Dose response curve of acetylcholine alone and in presence of different concentrations of atropine was plotted using isolated chicken ileum, chicken duodenum, rat ileum, and rat duodenum and their EC(50) values were compared. The effect of atropine in terms of its type of antagonism was predicted based on Schild plot and pA(2) values were obtained. The chicken ileum and duodenum were also evaluated for four- and three-point bioassay, respectively. The results suggested that acetylcholine produced a dose-dependent increase in contraction in both chicken and rat ileum and duodenum preparation. The concentration response curve of acetylcholine in chicken ileum shifted toward left side of rat ileum with a higher EC(50) value. Atropine shifted the concentration response curve of acetylcholine toward right with a change in EC(50) value. Schild plots indicated that antagonism produced by atropine was found to be competitive in nature. The pA(2) values of atropine were found significantly high with isolated chicken ileum as compared to rat ileum preparation. It is concluded that isolated chicken ileum and duodenum preparation can be employed for routine experiments of pharmacology subject and the use of these isolated preparations is a novel approach for managing pharmacological experiments and importantly, without sacrificing the experimental animals.

Pharmacological evaluation of fruits of Terminalia belerica Roxb. for antiulcer activity.

The antiulcer activity of 70% methanolic extract of fruits of Terminalia belerica Roxb. (Combretaceae) was evaluated using ethanol induced, aspirin induced, cold stress restraint and pylorus ligated ulcer in rats. The methanolic extract (100, 250, 500, 1000 mg/kg, p.o.) significantly suppressed the peptic ulcer induced by ethanol. Methanolic extract at a dose of 500 mg/kg showed, promising antiulcer activity hence, this dose was selected for further evaluation of antiulcer studies. The methanolic extract (500 mg/kg) showed significant (p<0.05) reduction in gastric volume, free acidity, total acidity, ulcer index, protein and pepsin content and increase in mucus content in pylorus ligated rats as compared to control. Treatment with Terminalia belerica methanolic extract further provided significant antiulcer protection against aspirin induced ulcers but not in cold stress restraint model. These results suggested that the 70% methanolic extract of Terminalia belerica increased resistance to necrotizing agents, providing a direct protective effect on the gastric mucosa and exhibited antiulcer effect.

Late-onset hepatic veno-occlusive disease post autologous peripheral stem cell transplantation successfully treated with oral defibrotide.

Hepatic veno-occlusive disease (VOD) remains one of the commonest and most serious complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the finding of the triad of painful hepatomegaly, hyperbilirubinemia, and unexplained fluid retention occurring within 21 days of the transplant. However, the uncommon clinical entity of late-onset VOD can occur even beyond 20 days and should be considered in the differential diagnosis of any liver disease of more than 3 weeks' duration. While mild cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide, a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. We describe a patient who presented 55 days post transplant with clinical features suggestive of VOD. Upon treatment with oral defibrotide, he showed complete resolution of the VOD.