Localization of language function in children: results of electrical stimulation mapping

OBJECT: The authors examined the localization of language sites and the frequency of naming errors at these sites in a population of children undergoing electrical stimulation mapping during surgeries in which epileptic foci and dominant hemisphere neoplasms were resected. The frequency with which essential language sites were found (that is, "the frequency of language sites") in children was compared with that of a population of adults who had undergone this procedure, to assess the relationship of age to the distribution of essential areas for language. METHODS: The results of electrical stimulation mapping to determine sites of naming and speech arrest in 26 children ranging in ages from 4 to 16 years are presented in this report. Mapping was performed in the intraoperative setting in eight patients and in the extraoperative setting, by stimulation across a subdural grid, in 18 patients. The frequency and distribution of essential language areas were analyzed in populations of different ages and according to the method used to obtain the map. Considerable variability was found in the localization of language sites. When the language site distribution in pediatric patients was compared with the language site distribution found previously in a population of patients older than 16 years of age, a relative paucity of language sites was found in all perisylvian cortices in the younger age group. This relationship was also found within the group of patients 16 years of age and younger, when segregated into two groups: those patients 8 years of age or younger, and those patients between 9 and 16 years of age. These findings are relevant to theories of the intrahemispheric organization of the cortex devoted to language function. CONCLUSIONS: The differences found between groups of younger and older patients in the frequencies of sites where stimulation produces naming errors was identified suggests the possibility that, with advancing age, maturational processes contribute new foci of cortex essential for language.     

Downregulation of bcl-2 expression in lymphoma cells by bcl-2 ARE-targeted modified,synthetic ribozyme

Synthetic ribozymes are catalytic RNA molecules designed to inhibit gene expression by cleaving specific mRNA sequences. We investigated the potential of synthetic ribozymes to inhibit bcl-2 expression in apoptosis defective bcl-2 overexpressing tumors. A chemically stabilized hammerhead ribozyme has been targeted to the A+U-rich regulative element of bcl-2 mRNA that is involved in bcl-2 gene switch-off during apoptosis. The design of the ribozyme was based on the results of probing accessibility of the RNA target in cellular extracts with antisense DNA. The ribozyme was lipotransfected to a bcl-2 overexpressing human lymphoma cell line (Raji). The cellular uptake of this ribozyme resulted in a marked reduction of both bcl-2 mRNA and BCL-2 protein levels and dramatically increased cellular death by apoptosis. Our results suggest a potential therapeutic application of such ribozyme for the treatment of bcl-2 overexpressing tumors.     

Circadian organization of serum electrolytes in physiological aging

Age-related structural and neurochemical changes occurring in the central nervous system have been related to changes in some rhythmometric parameters. In spite of their clinical importance, only a few studies have investigated the modifications over time of serum electrolytes in senescence. The aim of our study was to evaluate the circadian pattern of serum potassium, chloride, sodium, calcium and phosphorus in 30 clinically healthy elderly subjects, with no cognitive impairment, and to compare the findings with those given by 24 healthy young controls. The subjects were synchronized as regards their daily activities, sleeping/waking habits, time/quality of meals and dietary electrolyte intake. After an overnight fast, samples were taken beginning at 08.00 and every 4 h thereafter until 20.00, and every 2 h from 20.00 to 04.00. Both the young and the elderly subjects exhibited statistically significant circadian rhythms for all serum electrolytes considered. Our findings suggest that circadian organization of serum electrolytes is maintained in physiological aging, even though it should be noted that sodium and phosphorus acrophases differed significantly in the two experimental groups.     

Epidemiological monitoring of legionellosis: a case-control study in an university general hospital

The authors report the early results of a case-control study carried out about the risk of legionellosis. During the first year, they have tested urine samples from patients with unknown pneumonia, using a legionella-sensitive test for the detection of its antigen. Out of 171 samples, 9 have turned out to be positive (5.3%). Lifestyles, predisposing factors, possible sources of infection and stressful events were investigated.     

Intravaginal oestrogen and progestin administration: advantages and disadvantages

The vagina provides a local and a systemic route for delivering hormones for systemic effects and uterine targeting. Due to the 'uterine first-pass effect', hormones concentrate in the uterus and nearby tissues with low systemic exposure. Vaginal oestrogens, progesterone/progestins and danazol are currently used to obtain local (vagina and urethra), regional (uterus, pelvic structures) and systemic effects or contraception. Very low dosages of transvaginal oestrogens in the forms of creams, tablets and rings are effective for vaginal atrophy and urinary incontinence. To avoid endometrial stimulation, no deep vaginal application of low dosages for less than 6 months is recommended. For postmenopausal hormonal therapy by the vaginal route, progesterone is delivered directly to the uterus; the target organ for which it is designed. Worldwide, vaginal progesterone is employed for luteal phase support. Contraceptive vaginal rings offer the advantages of non-oral administration and sustained release. Vaginal administration of steroids is a promising option for the treatment of endometriosis.     

Homocysteinemia is inversely correlated with platelet count and directly correlated with sE- and sP-selectin levels in females homozygous for C677T methylenetetrahydrofolate reductase

Plasma homocysteine levels depend in part on the molecular nature of the methylenetetrahydrofolate reductase (MTHFR) and on blood folate intake. Little has been reported on platelet counts in the presence of hyperhomocysteinemia and MTHFR polymorphisms, with the exception of delayed platelet recovery in homozygous MTHFR C677T subjects after treatment with methotrexate for ovarian cancer. The aim of this investigation was to evaluate the possibility of a link between the platelet count and plasma homocysteine levels in different MTHFR variants in 165 female patients. Determinations of plasma homocysteine levels were by ELISA and of MTHFR polymorphisms (A1298C and C677T) were by inverse hybridization. Serum P- and E-selectin concentrations were obtained by ELISA. An inverse correlation (R=-0.88, P<0.001) was observed between blood platelet counts and plasma homocysteine levels in the women homozygous for MTHFR C677T. This correlation did not depend on pregnancy or other variables reported. Serum concentrations of sE- and sP-selectin, markers of endothelial and platelet activation, were significantly and positively correlated with homocysteine levels. These findings suggest that homocysteine affects platelet numbers in women with MTHFR C677T possibly consequent to endothelial and platelet activation.     

Development of molecular probes for the identification of extra interaction sites in the mid-gorge and peripheral sites of butyrylcholinesterase (BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors

Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis of the investigation of the active site gorge topology of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) and by using flexible docking procedures, molecular modeling studies formulated the hypothesis of extra interaction sites in the active gorge of hBuChE, namely, a mid-gorge interaction site and a peripheral interaction site. The design strategy led to novel BuChE inhibitors, balancing potency and selectivity. Among the compounds identified, the heterobivalent ligand 4m, containing an amide nitrogen and a sulfur atom at the 8-membered tether level, is one of the most potent and selective BuChE inhibitors described to date. The novel inhibitors, bearing postulated key features, validated the hypothesis of the presence of extra interaction sites within the hBuChE active site gorge.     

Naphtho[1,2-d]isothiazole acetic acid derivatives as a novel class of selective aldose reductase inhibitors

Acetic acid derivatives of naphtho[1,2-d]isothiazole (NiT) were synthesized and tested as novel aldose reductase (ALR2) inhibitors. The parent compound 11 exhibited a fair inhibitory activity (IC(50) = 10 muM), which was enhanced by 2 orders of magnitude by introducing a second carboxylic group at position 4 (13 and 14: IC(50) = 0.55 and 0.14 muM, respectively). Substitution of the acetic acid function with an apolar group gave inactive (29) or poorly active (25, 26, 30) compounds, thus demonstrating that the 2-acetic group is involved in the enzyme pharmacophoric recognition while the 4-carboxylic moiety has only an accessory role. The potent compounds 11, 13, 14, 26 all proved to be selective for ALR2, since none of them inhibited aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The isopropyl ester 31, a prodrug of 14, was found to be effective in preventing cataract development in severely galactosemic rats, when administered as an eyedrop solution. The theoretical binding mode of 13 and 14, obtained by docking simulations into the ALR2 crystal structure, was fully consistent with the structure-activity relationships in the NiT series.