In this study, a series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized and evaluated for antimycobacterial activity against Mycobacterium tuberculosis (MTB) H(37)Rv and isoniazid resistant M. tuberculosis (INHR-MTB). All the newly synthesized compounds were showing moderate to high inhibitory activities. The compound 6,7-dimethoxy-3-(4-chloro phenyl)-4H-indeno[1,2-c]isoxazole (4b) was found to be the most promising compound, active against MTB H(37)Rv and INHR-MTB with minimum inhibitory concentrations of 0.22 and 0.34 μM.
Objective: To report the use of Paliperidone in an adolescent with bipolar disorder primarily concerning its effectiveness and safety. Method: We present a case report of an adolescent with atypical presentation of bipolar disorder. The problem was complicated by poor liver function and poor compliance. Progress of the patient was recorded. Results: The patient showed dramatic improvement after 2 weeks on Paliperidone and has achieved the best level of functioning after almost 4 years on other treatment. Conclusion: The usage of Paliperidone was effective and safe in an adolescent with atypical bipolar disorder.
A series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized by the reaction of 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone with hydroxylamine hydrochloride. The title compounds were tested for their in vitro anti-HIV activity. Among the compounds, (4g) showed a promising anti-HIV activity in the in vitro testing against IIIB and ROD strains. The IC50 of both IIIB and ROD were found to be 9.05 microM and > 125 microM, respectively.
A series of novel isoxazole and pyrazoline derivatives has been synthesized and evaluated for their effects on the chemiluminescence and chemotactic activity of human phagocytes. Their effects on the chemotactic migration of isolated polymorphonuclear leukocytes (PMNs) and on the release of reactive oxygen species (ROS) during respiratory burst of human whole blood and PMNs were carried out using the Boyden chamber technique and luminol-based chemiluminescence assay, respectively. Of the compounds tested, compounds 8, 9, 11 and 12 exhibited higher inhibitory activity on the release of ROS (with IC50 values ranging from 5.6 to 8.4 μM) than acetylsalicylic acid (IC50 = 9.5 μ M). These compounds also showed strong inhibitory activity on the migration of PMNs with compound 8 exhibiting an IC50 value lower than that of ibuprofen. The results suggest that some of these isoxazole and pyrazoline derivatives have ability to modulate the innate immune response of phagocytes at different steps, indicating their potential as a source of new immunomodulatory agents.
This study investigates adsorption-desorption and the leaching potential of glyphosate and aminomethylphosphonic acid (AMPA) in control and amended-addition of cow dung or rice husk ash-acidic Malaysian soil with high oxide mineral content. The addition of cow dung or rice husk ash increased the adsorptive removal of AMPA. The isotherm data of glyphosate and AMPA best fitted the Freundlich model. The constant Kf for glyphosate was high in the control soil (544.873 mg g-1) followed by soil with cow dung (482.451 mg g-1) then soil with rice husk ash (418.539 mg g-1). However, for AMPA, soil with cow dung was high (166.636 mg g-1) followed by soil with rice husk ash (137.570 mg g-1) then the control soil (48.446 mg g-1). The 1/n values for both glyphosate and AMPA adsorptions were
Hand, foot and mouth disease (HFMD) is a highly contagious, world-wide distributed viral illness that affects predominantly children. It is caused by several enteroviruses, such as coxsackieviruses A6, A10, A16 and enterovirus 71. In most cases, HFMD follows a benign and self-limiting course. After an incubation period of 3 to 10 days, fever and sore throat, the first symptoms of the disease, appear. A few days later, maculopapular or vesicular eruptions form on the palms and soles as well as in the oral cavity. Since the year 2000, several large HFMD outbreaks have been reported in many Asian regions such as China, Malaysia and Vietnam. In some of these outbreaks, high incidences of severe progressive HFMD forms with some fatalities were observed. Such diseases have been caused primarily by enterovirus 71 strains and were characterized frequently by sudden onset of fever, encephalitis/meningitis and severe respiratory symptoms such as pulmonary edema. Further severe neurological and cardiac complications have also been observed during these outbreaks. Recently, some HFMD outbreaks caused by the coxsackievirus A6 have been reported in several parts of the world. These illnesses also affected adults and were characterized by more severe symptoms of "classical" HFMD. In addition, outbreaks of coxsackievirus-A6-associated HFMD in many countries were associated with onychomadesis, with the loss of nails occurring up to two months after initial symptoms. Treatment of "classical" HFMD is usually symptomatic, a generally recommended antiviral therapy does not exist. In severe HFMD cases, suitable treatment also encompasses mechanical ventilation, as well as the additional application of antiviral agents such as ribavirin. In the last years, several novel agents with good in vitro and in vivo activity against enteroviruses have been developed. A vaccine against HFMD is not yet available.
Several lines of evidence indicate that beta amyloid (β-A) production, neurofibrillary tangles and neuroinflammation are interrelated in the pathogenesis of Alzheimer's disease (AD). AD is associated with enhanced β-A production and accumulation resulting in neuroinflammation probably via activation of lipoxygenase (LOX) and cyclooxygenase (COX) pathways. Therefore, the present study was designed to investigate the role of LOX and COX inhibitors (zafirlukast and valdecoxib) in amyloidogenesis in β-A1-42 oligomer induced experimental AD in rats. The behavioral activities were assessed using actophotometer, novel object recognition test (ORT), Morris water maze (MWM) followed by biochemical assessments, determination of proinflammatory cytokines and mediators (TNF-α, IL-1β and PGE2), β-A1-42 levels and histopathological analysis. ICV administration of β-A1-42 oligomer produced significant impairment in memory consolidation. In addition to this significant increase in mito-oxidative stress, neuroinflammatory markers, acetylcholinesterase (AChE) toxicity, β-A1-42 level, neuronal cell death and neuroinflammation are more profound in β-A1-42 oligomer treated AD rats. Administration of zafirlukast (15 and 30mg/kg), and valdecoxib (5 and 10mg/kg) significantly improved the behavioral performances and showed significant reversal of mito-oxidative damage declining the neuroinflammation in β-A1-42 oligomer treated rats. Furthermore, more profound effects were observed at the sub-therapeutic dose combination of zafirlukast (15mg/kg) and valdecoxib (5mg/kg). The results of the present study indicate that protective effects of zafirlukast and valdecoxib are achieved through the blockade of release of LOX and COX metabolites therefore, representing a new therapeutic target for treating AD and other neurodegenerative disorders.