Episodic anterior drowsy theta in adults

The present study included 1300 adults with various clinical problems. We prospectively studied the EEG's of this population over an 18-month period. Ninety-two patients showed episodic generalized or frontal-central bursts of theta activity, occurring synchronously over both hemispheres in drowsiness (episodic anterior drowsy theta or EADT). We found no interaction between the parameters involving the above theta rhythms (amplitude, rhythmicity, topography and presence or absence in the waking EEG), demographic variables (age, sex), and clinical presentation. Our data, however, did suggest that the incidence of the EADT may be higher in young females. We also found a tendency for the EADT in otherwise abnormal EEGs to be rhythmic and present awake. Our data indicated that the presence of EADT is non-specific as to etiology.     

Infective endocarditis due to Salmonella typhi--a case report

Endocarditis is a rare complication of typhoid fever. We report a case in which Salmonella enterica serotype typhi was isolated from a case of endocarditis. The isolate was resistant to ampicillin, chloramphenicol and ciprofloxacin but sensitive to ceftriaxone, amikacin and gentamicin.     

mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity

The epithelial Na⁺ channel (ENaC) is essential for Na⁺ homeostasis, and dysregulation of this channel underlies many forms of hypertension. Recent studies suggest that mTOR regulates phosphorylation and activation of serum/glucocorticoid regulated kinase 1 (SGK1), which is known to inhibit ENaC internalization and degradation; however, it is not clear whether mTOR contributes to the regulation of renal tubule ion transport. Here, we evaluated the effect of selective mTOR inhibitors on kidney tubule Na⁺ and K⁺ transport in WT and Sgk1^–/– mice, as well as in isolated collecting tubules. We found that 2 structurally distinct competitive inhibitors (PP242 and AZD8055), both of which prevent all mTOR-dependent phosphorylation, including that of SGK1, caused substantial natriuresis, but not kaliuresis, in WT mice, which indicates that mTOR preferentially influences ENaC function. PP242 also substantially inhibited Na⁺ currents in isolated perfused cortical collecting tubules. Accordingly, patch clamp studies on cortical tubule apical membranes revealed that mTOR inhibition markedly reduces ENaC activity, but does not alter activity of K⁺ inwardly rectifying channels (ROMK channels). Together, these results demonstrate that mTOR regulates kidney tubule ion handling and suggest that mTOR regulates Na⁺ homeostasis through SGK1-dependent modulation of ENaC activity.     

Potential of endogenous estrogen receptor beta to influence the selective ER modulator ERbeta complex

The ratio of estrogen receptor beta (ERbeta) to ERalpha can alter the estrogen-like properties of tamoxifen. Transient transfection of ERbeta cDNA into cells can decrease the estrogen-like properties of the ERalpha:tamoxifen complex, whereas an increase in the amount of ERbeta is associated with tamoxifen-resistant breast cancer. We have addressed each of these hypotheses by examining well characterized laboratory models. We determined whether changes in endogenous ERbeta are responsible for the estrogen-like or antiestrogenic properties of tamoxifen or raloxifene in MDA-MB-231 cells transfected with cDNAs for ERalpha or mutants D351G, D351Y. We found that the amount of ERbeta mRNA in separate, stable transfectants of mutant ERalpha cDNA was always < 2% of ERalpha. Since at least a 50:50 mixture of ERalpha:ERbeta is needed to silence the tamoxifen:ERalpha complex, we conclude that insufficient ERbeta mRNA is available for selective ER modulation in stable transfectants of D351G and D351Y ERalpha. Similarly, to test the hypothesis that ERbeta is up-regulated and plays an important role during the development of tamoxifen-stimulated tumor growth, we quantitatively analyzed ERbeta and ERalpha mRNA in tamoxifen-na?ve (MCF-7:E2, ECC1:E2) and tamoxifen-stimulated tumors (MCF-7:TAM, EnCa 101:TAM). We found that ERbeta mRNA levels were not significantly elevated in tamoxifen-stimulated tumors and the ERalpha mRNA remained over 99% out of all ER species for all the tumors tested. The same results were also obtained when mRNA levels of ERbeta and ERalpha in a series of tamoxifen-na?ve and tamoxifen-resistant breast cancer was analyzed. We conclude that endogenous ERbeta may not play a dominant role in the modulation of the tamoxifen ERalpha complex, or in the development of tamoxifen-stimulated resistant tumor growth.     

Synthesis and Antitubercular Activity Evaluation of Novel Unsymmetrical Cyclohexane‐1,2‐diamine Derivatives

A library of unsymmetrical cyclohexane‐1,2‐diamine derivatives were synthesized and evaluated for their activity against Mycobacterium tuberculosis H37Rv in vitro. Out of the 46 compounds synthesized, eight compounds ( 11h , 13a , 13e , 13f , 14a , 14c , 14d , and 15d ) were found to be active at or below 6.25 µM concentration, with negligible toxicity to human red blood cells at a concentration much higher than the MIC₉₉. Compound 13a was the best active compound showing inhibition at 3.125–6.25 µM, and was found to be non‐hemolytic up to 500 µg/mL concentration.