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Biomedical subjects

Carmen Santos

Publications and source records attributed to Carmen Santos.

7 recordsLinked to original sources

Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis. METHODS: The expression of TLR-2, TLR-4 and CD14 in monocytes was analyzed by flow cytometry. To study the functional responses of these receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and the amounts of TNFalpha and IL-6 secreted were determined by ELISA. RESULTS: We found that the expression of TLR-2 was up-regulated in peripheral blood monocytes from COPD patients, either clinically stable or during AECOPD, as compared to never smokers or smokers with normal lung function. Upon stimulation with TLR-2 ligand monocytes from COPD patients secreted increased amounts of cytokines than similarly stimulated monocytes from never smokers and smokers. In contrast, the expressions of TLR-4 and CD14 were not significantly different between groups, and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not significantly different either. At discharge from hospital TLR-2 expression was down-regulated in peripheral blood monocytes from AECOPD patients. This could be due to the treatment with systemic steroids because, in vitro, steroids down-regulated TLR-2 expression in a dose-dependent manner. Finally, we demonstrated that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro TLR-2 expression in monocytes from never smokers. CONCLUSION: Our results reveal abnormalities in TLRs expression in COPD patients and highlight its potential relationship with systemic inflammation in these patients.

Aged↗

Sources and implications of basal nitric oxide in spontaneous contractions of guinea pig taenia caeci.

We examined in vitro the source and role of basal nitric oxide (NO) in proximal segments of guinea pig taenia caeci in nonadrenergic, noncholinergic (NANC) conditions. Using electron paramagnetic resonance (EPR), we measured the effect of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), the neuronal blocker tetrodotoxin (TTX, 10(-6) M), or both on spontaneous contractions and on the production of basal NO. Both L-NAME and TTX, when tested alone, increased the amplitude and frequency of contractions. NO production was abolished by L-NAME and was inhibited by 38% by TTX. When tested together, L-NAME in the presence of TTX or TTX in the presence of L-NAME had no further effect on the amplitude or frequency of spontaneous contractions, and the NO production was inhibited. These findings suggest that basal NO consists of TTX-sensitive and TTX-resistant components. The TTX-sensitive NO has an inhibitory effect on spontaneous contractions; the role of TTX-resistant NO is unknown.

Animals↗

Long-term (72 hours) preservation of rat lungs.

OBJECTIVE: We sought to investigate whether the addition of ethanol to a preservation solution (as an antifreeze agent) might allow a reduction of the storage temperature to 0 degrees C without causing freezing damage and improve lung function after prolonged (72 hours) ischemia. METHODS: Lungs from Sprague-Dawley rats were ventilated and perfused ex vivo at 37 degrees C for 60 minutes in the following experimental groups: (1) the no ischemia and reperfusion (no I-R) group (n = 7), in which lungs were studied immediately after harvesting; (2) the LPD24 (n = 7) and (3) LPD72 (n = 8) groups, in which, after harvesting, lungs were flushed and immersed in low-potassium dextran solution and stored deflated at 10 degrees C for 24 and 72 hours, respectively, until reperfusion; and (4) the TEST72 group (n = 9), in which lungs were flushed and immersed in Krebs-Henseleit buffer with added ethanol (10 mL/L) after harvesting and stored deflated at 0 degrees C for 72 hours until reperfusion. RESULTS: Compared with the no I-R group, the other 3 groups had worse lung function, higher lung water content, and evidence of cell injury at reperfusion (P <.01). However, lung function at reperfusion (assessed on the basis of either effluent Po(2), peak airway pressure, or mean arterial pulmonary pressure) was better (P <.01) in the TEST72 group than in the LPD24 or LPD72 groups. Paradoxically, lung cell structure was better preserved in the LPD24 group than in the TEST72 group (or the LPD72 group). CONCLUSIONS: In this experimental model of rat lung ischemia-reperfusion injury, a low preservation temperature (0 degrees C) combined with the addition of ethanol to the preservation solution improves lung function at reperfusion after 72 hours of ischemia but fails to maintain lung cell structure.

Animals↗

Sleep/wake cycles in the dark: sleep recorded by polysomnography in 26 totally blind subjects compared to controls.

OBJECTIVES: To evaluate subjective sleep difficulties and nocturnal sleep with polysomnography in 26 completely blind subjects, living in normal social environments and to compare the findings with those of matched controls. METHODS: Twenty-six blind individuals with no light perception and free-running melatonin rhythms, as assessed by measurements of urinary and salivary 6-sulfatoxymelatonin, were polygraphically monitored. Actigraphy and Braille sleep logs were obtained from the individuals for 14 days. Their sleep was compared to that of matched controls. RESULTS: Blind individuals were 'free-running' despite normal and regular social interaction. Each had ordinary working conditions and/or a family life with seeing spouse and children. Actigraphy obtained on 14 successive days showed the presence of small amount of daytime 'sleep' - 24.7+/-25.1 min per day. Total sleep time, sleep latency, sleep efficiency, and total REM sleep were significantly lower than in matched controls. Working blind subjects had a slightly higher total sleep time than those retired and unemployed. Congenital blindness, acquired blindness, presence of bilateral prosthetic eyes or presence of normal human eyes did not produce different nocturnal sleep and 'free-running' pattern results. CONCLUSIONS: Reduced total sleep time and other sleep abnormalities were associated with the complaint of daytime sleepiness and poor sleep in blind subjects. The abnormalities of sleep, which may be related to the free-running condition, present an additional challenge for these subjects, who are already severely impaired by their complete lack of vision.

Adult↗

Herpes simplex uveitis.

BACKGROUND: Uveitis in herpes simplex virus (HSV) ocular disease is usually associated with corneal stromal disease. It has generally been believed that herpetic uveitis in the absence of corneal disease is very rare. When seen it is usually attributed to varicella zoster virus (VZV) infections. The diagnosis of uveitis caused by herpes simplex is often not diagnosed resulting in inadequate treatment and a poor visual result. METHODS: Seven patients from a large uveitis practice who presented with a clinical picture of: anterior uveitis and sectoral iris atrophy without keratitis, a syndrome highly suggestive of herpetic infection, are reported. Polymerase chain reaction (PCR) was done in the aqueous of four of them and was positive for HSV. One patient had bilateral disease. Most of the patients also had severe secondary glaucoma. RESULTS: Of the seven patients presented five had no history of any previous corneal disease. Two had a history of previous dendritic keratitis which was not active at the time of uveitis development. One patient with bilateral disease was immunosuppressed at the time when the uveitis developed. Six of the seven patients had elevated intraocular pressures at the time of uveitis and five required glaucoma surgery. Intractable glaucoma developed in two patients leading to rapid and severe visual loss despite aggressive management. CONCLUSION: Findings suggest that uveitis without corneal involvement may be a more frequent manifestation of ocular herpes simplex disease than previously thought. Absence of corneal involvement delays a correct diagnosis and may worsen visual outcome. Primary herpetic uveitis (when there is no history of previous corneal disease) seems to be more severe than the uveitis in patients with previous corneal recurrences. The associated glaucoma may be a devastating complication.

Acyclovir↗