Synthesis and antiplatelet, antiinflammatory, and antiallergic activities of substituted 3-chloro-5,8-dimethoxy-1,4-naphthoquinone and related compounds

2-Amino (6), 2-alkylamino (7-8), 2-methoxy (9), 2-acetamido (10), and 5,8-diacetoxy (11) derivatives of the lead compound 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (4) were synthesized, together with 6,7-dichloro-5,8dimethoxy-1,4-naphthoquinone (5), a positional isomer of 4. Antiplatelet, antiinflammatory, and antiallergic activities were evaluated, and most compounds were quite potent in all assays. Compounds 5 and 9-11 were especially active; however, 5 was ineffective against neutrophil superoxide formation, and 10 was ineffective against mast cell degranulation.     

Dermatomyositis

Dermatomyositis is a rare inflammatory myopathy with characteristic skin manifestations and muscular weakness. The disease can be categorized as adult idiopathic, juvenile, or amyopathic dermatomyositis as well as that associated with a connective tissue disease or a malignancy. Immunologic factors are most likely involved in the pathogenesis of the disease; however, genetic and environmental issues may also play important roles. Treatment with immunosuppressive agents has proved successful in the majority of patients, although significant morbidity still occurs.     

Synthesis and antitumor activity of novel benzophenone derivatives

Novel benzophenone derivatives were synthesized and screened for cytotoxic and antitumor activity. Friedel-Crafts condensation was employed to construct the benzophenone skeleton. Among the compounds synthesized, morpholino and thiomorpholino benzophenones 3a-d exhibited potent cytotoxic activity against P388 murine leukemia and PC-6 human lung carcinoma cells in vitro, and compounds 3a, 3c, and 3j, when administered intraperitoneally, showed significant antitumor activity against the malignant ascites caused by intraperitoneal inoculation of P388 cells in mice.     

Role of hepatic resection in surgery for bilateral intrahepatic stones

The effect of phenylephrine-induced reflex parasympathetic stimulation on QT interval and its dispersion was studied in 16 healthy subjects with a history of paroxysmal supraventricular tachycardia, both during sinus rhythm and during atrial pacing. Results demonstrate that rapid reflex parasympathetic stimulation does not influence QT interval duration or QT dispersion, and also emphasize the inappropriateness of Bazett's formula, the need for comparison of QT intervals during identical heart rates, and the importance of analyzing all 12 leads of a standard electrocardiogram when assessing the effects of various interventions on the QT interval.     

Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3 ) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4 ), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.     

Channel Bed Slope Effect on the Height of Gravity Waves Produced by a Sudden Downstream Discharge Stoppage

We derive a simple analytical correction of a well-known standard formulation of the gravity wave height produced in a prismatic channel due to a sudden discharge stoppage at the downstream end of the channel. The proposed analytical correction considers the vertical growth of the wave and, as a result, takes into account the effect of the channel bed slope on the wave height. This simple correction is useful to be considered in preliminary designs of relatively long channels subject to unsteady flow conditions.     

Sympathetic response to stimulation of the pontine A5 region in conscious rabbits

OBJECT: This study is a retrospective analysis of clinical data obtained in 28 patients affected by obstructive hydrocephalus who presented with signs of midbrain dysfunction during episodes of shunt malfunction. METHODS: All patients presented with an upward gaze palsy, sometimes associated with other signs of oculomotor dysfunction. In seven cases the ocular signs remained isolated and resolved rapidly after shunt revision. In 21 cases the ocular signs were variably associated with other clinical manifestations such as pyramidal and extrapyramidal deficits, memory disturbances, mutism, or alterations in consciousness. Resolution of these symptoms after shunt revision was usually slow. In four cases a transient paradoxical aggravation was observed at the time of shunt revision. In 11 cases ventriculocistemostomy allowed resolution of the symptoms and withdrawal of the shunt. Simultaneous supratentorial and infratentorial intracranial pressure recordings performed in seven of the patients showed a pressure gradient between the supratentorial and infratentorial compartments, with a higher supratentorial pressure before shunt revision. Inversion of this pressure gradient was observed after shunt revision and resolution of the gradient was observed in one case after third ventriculostomy. In six recent cases, a focal midbrain hyperintensity was evidenced on T2-weighted magnetic resonance imaging sequences at the time of shunt malfunction. This rapidly resolved after the patient underwent third ventriculostomy. CONCLUSIONS: It is probable that in obstructive hydrocephalus, at the time of shunt malfunction, the development of a transtentorial pressure gradient could initially induce a functional impairment of the upper midbrain, inducing upward gaze palsy. The persistence of the gradient could lead to a global dysfunction of the upper midbrain. Third ventriculostomy contributes to equalization of cerebrospinal fluid pressure across the tentorium by restoring free communication between the infratentorial and supratentorial compartments, resulting in resolution of the patient's clinical symptoms.     

Issues and Techniques in Networked-Based Distributed Healthcare: Overview

For telemedicine to reach its potential in the Internet2 environment,significant progress must be made in a number of areas. The emergingtelecommunications will include the Internet2 between medicalinstitutions and emerging broadband loop and wireless technologiesfor interconnections to homes. Within the technical environment,problems that must be addressed include the development of robotic-controlled,remote-monitoring devices unique to the various medical specialties;the encoding, transmission, and decoding of raw data specificto the specialized needs of various medical application areas;and the reduction of data for storage and retrieval in patientrecords. Institutionally, human factor and information accessissues with respect to physicians, patients, and non-physicianhealthcare providers must be addressed; healthcare insuranceprovider policies, government regulation, and state licensinglaws must be adapted for a new paradigm of healthcare delivery;and the philosophy of capital investment for the delivery ofhealthcare must be revised.Many current practiceswill be supplanted by home healthcare alternatives, the use ofpatient-initiated preventive healthcare initiatives, and remote-clinicactivity. These applications will result in central record archivingsystems; the need for encryption schemes, virus protection, andvandalism protection; extensive, additional connectivity betweenhealthcare providers and professionals; and new commercial playersin the healthcare arena.The hot applicationareas will include women's health, children's health, healthcarefor senior citizens, home healthcare, well-patient monitoring,and early-detection of medical problems.