Brain hemodynamic changes in preterm infants after maintenance dose caffeine and aminophylline treatment

OBJECTIVE: To investigate the acute effects of low-dose caffeine and aminophylline on cerebral blood flow in preterm infants, using both near-infrared spectroscopy (NIRS) and cerebral Doppler ultrasonography. METHODS: Preterm infants with a gestational age of <32 weeks and birth weight of <1,500 g were randomized to receive either caffeine or aminophylline treatment for apnea of prematurity. The study period went from 30 min before to 60 min after the administration of the maintenance dose of pure caffeine (2.5 mg/kg once a day) or aminophylline (1.25 mg/kg twice a day). NIRS was used to measure changes in oxygenated hemoglobin (O(2)Hb), deoxygenated hemoglobin (HHb), oxidized-reduced cytochrome aa3 (CtOx), and mean cerebral oxygen saturation (SmO(2) = O(2)Hb/total Hb). Changes in cerebral blood volume (DeltaCBV) after caffeine or aminophylline administration were calculated. Cerebral blood flow velocity (CBV) in the pericallosal artery was evaluated by cerebral Doppler ultrasounds. RESULTS: Data collected by NIRS and cerebral Doppler ultrasounds did not show significant differences before and after caffeine treatment. We observed a significant increase in O(2)Hb and HHb concentration and in CBV at 30 min after the infusion of aminophylline, which tended to return to baseline at the end of the study period. CONCLUSION: Caffeine does not significantly affect brain hemodynamics, while aminophylline induces a significant transient increase in O(2)Hb and HHb concentration and CBV.     

Thin cutaneous malignant melanomas (< or =1.5 mm): identification of risk factors indicative of progression

BACKGROUND: Although thin cutaneous melanomas generally have a favorable prognosis, in some cases they may undergo progression. The current study was undertaken to identify variables that may predict a more aggressive clinical outcome in these patients. In addition to classic clinicopathologic features, the authors tested the prognostic impact of three new morphometric quantitative parameters: 1) tumor thickness plus regression thickness (T+R), 2) percentage of skin thickness infiltrated by tumor cells (T/S ratio), and 3) percentage of skin thickness infiltrated by tumor cells and regression ([T+R]/S ratio). METHODS: The authors retrospectively evaluated 287 patients with invasive cutaneous melanoma < or = 1.5 mm in thickness. Disease free survival rates (Kaplan-Meier method) were compared by using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on progression. Progression was defined as any documented cutaneous local and/or distant metastasis. RESULTS: Thirty-two of the 287 patients (11.1%) underwent disease progression. The overall 5-year and 10-year disease free survival rates were 89.3% and 84.6%, respectively. In the univariate analysis, the following factors were found to be significant predictors of progression: male gender (P = 0.01), acral-lentiginous histotype (P = 0.02), tumor thickness (P = 0.005), T+R (P = 0.001), T/S ratio > or = 50% (P = 0.03), (T+R)/S ratio > or = 50% (P = 0.006), vertical growth phase (P = 0.04), and absence of inflammatory response (P < 0.0001). Conversely, age, site, and Clark's level did not affect the risk of recurrences and/or metastases significantly. In the multivariate analysis, only T+R (P = 0.009) and inflammatory response (P < 0.0001) were found to be independent predictors of progression. Five-year disease free survival rates according to presence versus absence of inflammatory response were 93.4% and 63.8%, respectively (P < 0.0001). CONCLUSIONS: In the current study, peritumoral and intratumoral inflammatory infiltrate and T+R were found to be strong independent predictors of progression in thin cutaneous melanomas.     

Beta-lactamase evaluation of the amoxycillin-clavulanate association

The capability of potassium clavulanate to protect amoxycillin from destruction by three partially purified beta-lactamases (from E. cloacae, B. cereus 569/H9 and E. coli R-TEM) was evaluated. The enzymatic inhibition was determined spectrophotometrically by assessing the ability of either amoxycillin or potassium clavulanate or their combination (at a 7:1 ratio by weight) to prevent the hydrolysis of a chromogenic substrate (nitrocefin) after different pre-incubation times, thus determining the IC50 and Ki values. Potassium clavulanate significantly reduced the IC50 values of amoxycillin for B. cereus and TEM enzymes by a factor ranging from 500 to 1200, by inhibiting these beta-lactamases at concentrations ranging from 4 to 0.008 microM. However, clavulanic acid was quite ineffective against type I enzymes (from E. cloacae), while amoxycillin was found to be sufficiently stable (IC50 of 0.8-1.4 microM).     

Screening of estrogen-like activity of mineral water stored in PET bottles

Bottled mineral water consumption is steadily rising in the World. Italy is the largest natural mineral water consumer in Western Europe, about 200L per capita per annum. Recently, research has concentrated upon emerging toxicological problems such as the presence in drinking water of substances which interfere with the function of the endocrine system; defined as endocrine disruptors (EDs). The aim of this study was to assess the risk of exposure of the population to chemicals with estrogen-like activity through mineral water consumption by monitoring the presence of estrogenic compounds in mineral water bottled in polyethylene terephthalate (PET). A solid phase extraction (SPE) with C18 cartridges was carried out. The estrogenic activity of the extracts was assayed using a yeast assay expressing the human estrogen receptor alpha (hERalpha). This preliminary study shows that more than 90% of the water samples did not exhibit any appreciable estrogenic activity. The highest estrogenic activity detected in water extracts was equivalent to the activity induced by 23.1ng/L of the natural hormone 17beta-estradiol. Some mineral water samples showed toxicity on yeast cells.     

Restrictions on biological adaptation in language evolution

Language acquisition and processing are governed by genetic constraints. A crucial unresolved question is how far these genetic constraints have coevolved with language, perhaps resulting in a highly specialized and species-specific language “module,” and how much language acquisition and processing redeploy preexisting cognitive machinery. In the present work, we explored the circumstances under which genes encoding language-specific properties could have coevolved with language itself. We present a theoretical model, implemented in computer simulations, of key aspects of the interaction of genes and language. Our results show that genes for language could have coevolved only with highly stable aspects of the linguistic environment; a rapidly changing linguistic environment does not provide a stable target for natural selection. Thus, a biological endowment could not coevolve with properties of language that began as learned cultural conventions, because cultural conventions change much more rapidly than genes. We argue that this rules out the possibility that arbitrary properties of language, including abstract syntactic principles governing phrase structure, case marking, and agreement, have been built into a “language module” by natural selection. The genetic basis of human language acquisition and processing did not coevolve with language, but primarily predates the emergence of language. As suggested by Darwin, the fit between language and its underlying mechanisms arose because language has evolved to fit the human brain, rather than the reverse.