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Biomedical subjects

R Sala

Publications and source records attributed to R Sala.

At least 19 recordsLinked to original sources

Sperm DNA fragmentation in a random sample of the Spanish boar livestock.

A collection of 180 chilled boar semen samples, randomly chosen from stocks currently used for routine characterization of standard seminal quality, were studied for DNA fragmentation status using the sperm chromatin dispersion test and the DNA fragmentation index (DFI: percent of abnormal cell versus normal cells for DNA fragmentation) was determined. Values for sperm motility, acrosome status, coiled tails and abnormal head morphology, including presence and position of cytoplasmic droplets were also obtained. The DFI in the whole sample presented a wide range of variation with values oscillating between practically 0% and 47.95% and do not fit to a normal distribution. The most frequent classes (83.3%) presented a DFI lower than a 5%. Significant correlations between sperm DNA fragmentation and sperm motility, acrosome status, frequency of distal droplets, coiled tails and abnormal head morphology, were not observed. However, the presence of proximal cytoplasmic droplets showed a significant correlation with the level of DNA fragmentation observed in the ejaculated spermatozoa.

Acrosome↗

A comparison of models for dynamic life tables. Application to mortality data from the Valencia Region (Spain).

The graduation of mortality data aims to estimate the probabilities of death at age x, q ( x ), by means of an age-dependent function, whose parameters are adjusted from the crude probabilities that are directly obtainable from the data. However, current life tables have a problem, the need for periodic updates due to changes in mortality over short periods of time. The table containing mortality rates for different ages in different years, q ( xt ), is called a dynamic life table, which captures mortality variation over time. This paper proposes a review of the most commonly used dynamic models and compares the results obtained by each of them when applied to mortality data from the Valencia Region (Spain). The result of the comparison leads us to the conclusion that the Lee-Carter method offers the best results for both sexes, while that based on Heligman and Pollard functions provides the best fit for men alone. Our working method is of additional interest as it may be applied to mortality data for a wide range of ages in any geographical location, allowing the most appropriate dynamic life table to be selected for the case at hand.

Humans↗

Plasma homocysteine and folate levels in patients with chronic plaque psoriasis.

BACKGROUND: Hyperhomocysteinaemia is a well-known risk factor for cardiovascular diseases. Patients with severe chronic plaque psoriasis have a higher risk of death due to arterial and/or venous thrombosis. OBJECTIVES: To investigate the relationship among plasma homocysteine and folate levels and severity of chronic plaque psoriasis in a selected cohort of patients with psoriasis without known risk factors for acquired hyperhomocysteinaemia. METHODS: We performed a case-control study in 40 patients with chronic plaque psoriasis and 30 age- and sex-matched healthy controls. Cases and controls were selected excluding individuals with conditions or diseases associated with acquired hyperhomocysteinaemia, and were also asked to stop alcohol and coffee consumption for 1 week before blood sampling. The plasma levels of homocysteine and folic acid were measured and were correlated with the severity of psoriasis (Psoriasis Area and Severity Index, PASI). RESULTS: Patients with psoriasis had plasma homocysteine levels higher than controls (mean +/- SD 16.0 +/- 5.6 vs. 10.4 +/- 4.7 micro mol L(-1); P < 0.001). Conversely, folic acid levels were lower in patients with psoriasis compared with controls (mean +/- SD 3.6 +/- 1.7 vs. 6.5 +/- 1.7 nmol L(-1); P < 0.001). Plasma homocysteine levels in patients with psoriasis correlated directly with disease severity (PASI) and inversely with folic acid levels. Plasma folic acid levels were inversely correlated with the PASI. No abnormalities of plasma vitamin B(6) and B(12) were found. CONCLUSIONS: Patients with psoriasis may have a tendency to hyperhomocysteinaemia, which may predispose to higher cardiovascular risk. Dietary modification of this risk factor appears relevant to the global management of patients with moderate to severe psoriasis.

Adolescent↗

An Early Pleistocene hominin mandible from Atapuerca-TD6, Spain.

We present a mandible recovered in 2003 from the Aurora Stratum of the TD6 level of the Gran Dolina site (Sierra de Atapuerca, northern Spain). The specimen, catalogued as ATD6-96, adds to the hominin sample recovered from this site in 1994-1996, and assigned to Homo antecessor. ATD6-96 is the left half of a gracile mandible belonging to a probably female adult individual with premolars and molars in place. This mandible shows a primitive structural pattern shared with all African and Asian Homo species. However, it is small and exhibits a remarkable gracility, a trait shared only with the Early and Middle Pleistocene Chinese hominins. Furthermore, none of the mandibular features considered apomorphic in the European Middle and Early Upper Pleistocene hominin lineage are present in ATD6-96. This evidence reinforces the taxonomic identity of H. antecessor and is consistent with the hypothesis of a close relationship between this species and Homo sapiens.

Adult↗

A comprehensive overview of photodynamic therapy in the treatment of superficial fungal infections of the skin.

Photodynamic therapy (PDT) is a two-step procedure, involving the topical or systemic administration of a photosensitizer followed by selective illumination of the target lesion with visible light, which triggers the oxidative photodamage and subsequent cell death within the target area. In dermatology, PDT has proven to be a useful treatment for a variety of malignant tumors and selected inflammatory diseases. In addition, PDT of several infective viral or bacterial skin diseases has been investigated. These investigations grew out of the positive findings of studies of another important use of PDT: that of disinfection of blood products. Up to now, little has been published concerning the application of PDT to fungi, probably due to the fact that research funding has been mainly directed towards blood disinfection, and these pathogens show a low risk of transfusion transmission. However, preliminary findings have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro by administering photosensitizers belonging to four chemical groups: phenothiazine dyes, porphyrins and phthalocyanines, as well as aminolevulinic acid, which, while not a photosensitizer in itself, is effectively metabolized into protoporphyrin IX. Besides efficacy, PDT has shown other benefits. First, the sensitizers used are highly selective, i.e., fungi were killed at combinations of drug and light doses much lower than that needed for a similar effect on keratinocytes. Second, all investigated photosensitizers lack genotoxic and mutagenic activity. Finally, the hazard of selection of drug resistant fungal strains was never reported. This paper intends to provide a comprehensive overview of investigative studies about the effects of PDT on yeasts and dermatophytes, and bring attention to this application of PDT which we believe very important in that skin mycosis is so common and PDT is not only cost-effective, but also has the advantages of being highly selective and avoiding the occurrence of drug resistant strains.

Animals↗

Photodynamic therapy of interdigital mycoses of the feet with topical application of 5-aminolevulinic acid.

BACKGROUND: Findings of in vitro studies have demonstrated that dermatophytes and yeasts can be effectively photosensitized after topical delivery of 5-aminolevulinic acid (ALA). This procedure, called photodynamic therapy (PDT), seems to lack mutagenic activity and hazard of selection of drug-resistant strains. METHODS: Twenty percent ALA preparation in Eucerin cream was applied under an occlusive dressing to skin lesions of nine patients with clinical and microbiological evidence of interdigital mycosis of the feet. After 4 h, lesions were irradiated with 75 J/cm(2) of broad-band red light. Interdigital lesions of the other foot served as control (treated with only light or only ALA). After 7 days from the first treatment, no further treatment was delivered if lesions were not clinically evident and direct microscopic examination was negative. Otherwise, three additional weekly treatments were delivered. Four weeks after the last treatment, patients had a final follow-up clinical and laboratory examination. RESULTS: Clinical and microbiological recovery was seen in six out of nine patients after one (four cases) or four (two cases) treatments. However, after 4 weeks, recurrences were seen in four patients. Overall tolerability was always good. CONCLUSION: Under the conditions employed in the present study, ALA-PDT had good therapeutic effects on interdigital mycosis of the feet. However, recurrences were quick. In vivo environmental conditions, i.e. temperature, humidity and pH of the interdigital skin, could induce a poor cell uptake of ALA and a deficient biosynthesis of photosensitizing protoporphyrin IX. In addition, the irregular tridimensional shape of this peculiar anatomical area could lead to a non-uniform delivery of light and/or ALA cream. However, the present results can stimulate further studies on the PDT of superficial skin mycoses.

Administration, Cutaneous↗

Single-agent epirubicin as primary chemotherapy in T2-T3, N0-N2, M0 breast carcinoma: 6-year follow-up.

OBJECTIVE: Single-agent epirubicin was tested as primary chemotherapy treatment in patients with early breast cancer >3 cm. METHODS: 100 women with locally advanced breast cancer >3 cm were treated with three cycles of single-agent epirubicin at a dose of 120 mg/m2. All patients showing tumor shrinkage to less than 3 cm were considered candidates for conservative surgery (quadrantectomy); in the remaining patients modified radical mastectomy was carried out. Postsurgical treatment consisted of CMF chemotherapy except for postmenopausal node-positive, estrogen-positive patients who were assigned to hormonal treatment with tamoxifen and postmenopausal node-negative, estrogen-positive ones who did not receive any treatment. RESULTS: Quadrantectomy was carried out in 71 patients. At the median follow-up time of 69 months, the relapse rate was 29.6% among patients who underwent quadrantectomy (21 out of 71) and 58.6% among patients who underwent modified radical mastectomy (17 out of 29). CONCLUSIONS: Single-agent chemotherapy with anthracyclines could appear to be an effective treatment in inducing a tumor downstaging in patients with early breast cancer >3 cm. This treatment can be administered outside clinical trials in patients who desire to preserve their body integrity. Further prospective, randomized trials are needed in order to validate and better define the role of epirubicin in the neoadjuvant strategy of breast cancer patients.

Adult↗

Early detection of skin cancer (EDISCIM) through the use of non-invasive confocal imaging.

In the past 15 years the number of malignant melanomas and non-melanoma skin cancer, (i.e. squamous cell carcinoma, basal cell carcinoma), have increased dramatically throughout the whole world, in particular among people with white skin. For example, in Germany the number of new cases of melanoma is about 10 to 12 per 100,000 people, (for basal cell carcinoma as a non-melanoma skin cancer 140 per 100,000), the absolute number of annual new cases of melanoma is an estimated 9,000 to 10,000, and the increasing rate is 5 to 10%. However, there are more than 40 differential diagnoses for skin cancer which makes it difficult even for expert dermatologists to give correct diagnosis, (estimated 75% correct diagnoses). This figure is even worse for doctors from other specialities. There is only a chance of high cure rates when skin tumours are detected at an early stage. The prognosis of skin cancer is dependent very much on the thickness, (as a sign of invasiveness), of the tumour and the number of mitotic figures in the tumour, (as a sign of proliferation activity). However, the final diagnosis of skin cancer is usually done by biopsy, the sample being investigated by a specialist. This is an invasive method, which is painful for the patient and might require several cuts and samples taken before being absolutely certain. Due to the potential risk of dissemination of tumour cells, taking an incisional biopsy is obsolete in malignant melanoma. Therefore the correct diagnosis of malignant melanoma can be made only after a total removal of the lesion and consecutive histopathological examination. The EDISCIM project intends to develop a system for the early diagnosis of skin cancer which uses confocal imaging for the non-invasive diagnosis of the upper layers of the skin that aids the physician in the analysis of the images and therefore with the diagnosis, allows for potential remote diagnosis by specialist dermatologists via tele-diagnosis if need be. The objectives of the system are Captures microscopic images of the skin by confocal imaging, Processes and records these images in real time, Compares these images against a knowledge base of known skin symptoms, Displays the results in a suitable interface to the physician performing the diagnosis, And supports the online telematic support by specialists.

Animals↗

The adaptive regulation of amino acid transport system A is associated to changes in ATA2 expression.

The activity of transport system A for neutral amino acids is adaptively stimulated upon amino acid starvation. In cultured human fibroblasts this treatment causes an increase in the expression of the ATA2 system A transporter gene. ATA2 mRNA increase and transport stimulation are suppressed by system A substrates, but they are unaffected by other amino acids. Supplementation of amino acid-starved cells with substrates of system A causes a decrease in both ATA2 mRNA and system A transport activity. These results suggest a direct relationship between ATA2 expression and system A transport activity.

Amino Acid Transport Systems↗

Amino acid depletion activates TonEBP and sodium-coupled inositol transport.

The expression of the osmosensitive sodium/myo-inositol cotransporter (SMIT) is regulated by multiple tonicity-responsive enhancers (TonEs) in the 5'-flanking region of the gene. In response to hypertonicity, the nuclear abundance of the transcription factor TonE-binding protein (TonEBP) is increased, and the transcription of the SMIT gene is induced. Transport system A for neutral amino acids, another osmosensitive mechanism, is progressively stimulated if amino acid substrates are not present in the extracellular compartment. Under this condition, as in hypertonicity, cells shrink and mitogen-activated protein kinases are activated. We demonstrate here that a clear-cut nuclear redistribution of TonEBP, followed by SMIT expression increase and inositol transport activation, is observed after incubation of cultured human fibroblasts in Earle's balanced salts (EBSS), an isotonic, amino acid-free saline. EBSS-induced SMIT stimulation is prevented by substrates of system A, although these compounds do not compete with inositol for transport through SMIT. We conclude that the incubation in isotonic, amino acid-free saline triggers an osmotic stimulus and elicits TonEBP-dependent responses like hypertonic treatment.

Adolescent↗

Nurses and requests for female genital mutilation: cultural rights versus human rights.

In this article we focus on female genital mutilation. We analyse this problem as one of the most important issues of multiculturalism, which is also coming to the attention of the public in Italy as a consequence of the growing number of immigrants from African countries. The fundamental problem is about the acceptability of this practice: can female genital mutilation be permitted and, if so, on what basis? We will try to cope with this as a genuine conflict between culture-relative values and universal values, such as human rights. Some attention will be drawn to Italian law. Finally, the impact on nurses of requests for genital mutilation will be described.

Africa↗

Avidin expression during chick chondrocyte and myoblast development in vitro and in vivo: regulation of cell proliferation.

Avidin is a major [35S]methionine-labeled protein induced by bacterial lipopolysaccharide (LPS) and interleukin 6 (IL-6) in cultured chick embryo myoblasts and chondrocytes. It was identified by N-terminal sequencing of the protein purified from conditioned culture medium of LPS-stimulated myoblasts. In addition, avidin was secreted by unstimulated myoblasts and chondrocytes during in vitro differentiation; maximal expression being observed in differentiated myofibers and hypertrophic chondrocytes. In developing chick embryos, immunohistochemistry revealed avidin in skeletal muscles and growth plate hypertrophic cartilage. Avidin was secreted into culture as a biologically active tetramer. Exogenous avidin added to the medium of proliferating chondrocytes progressively inhibited cell proliferation, whereas addition of avidin to differentiating chondrocytes in suspension allowed full cell differentiation. No toxic effects for the cells were observed in both culture conditions. Western blots of samples from cytosolic extracts using alkaline-phosphatase-conjugated streptavidin showed three biotin-containing proteins. Acetyl-CoA carboxylase was identified by specific antibodies. Based on these data, we propose that avidin binds extracellular biotin and regulates cell proliferation by interfering with fatty acid biosynthesis during terminal cell differentiation and/or in response to inflammatory stimuli.

Animals↗

Robotics in child neurosurgery.

We felt there was a need for a new device with "minimal invasive" tracking hardware, to be used in image-guided neurosurgery, and the system we designed to fill this need is now presented. It combines precision of movement, stability and self-positioning capabilities together with optically tracked registration and procedural control within the structure of a surgical microscope. The results are reduced setup time and minimal "distraction" from the procedure itself, factors of special relevance in child neurosurgery. The system is composed of a six-axis industrial robot suitable for use in the operating room, carrying a surgical microscope. Three progressive scan-synchronized infrared cameras mounted around the lenses of the scope are used to register the patient's position and track surgical instruments with reference to the registered space. Orientation of the microscope during surgery is obtained with a six-axis joystick used as a microscope handle. The system has been clinically used in 14 cases, and it has proven itself to be reliable, providing the expected performance advantages. The implementation of a tracked ultrasound or endoscope intraoperative imaging source is also described.

Brain Diseases↗

Release of dopamine from human neocortex nerve terminals evoked by different stimuli involving extra- and intraterminal calcium.

The release of [(3)H]-dopamine ([(3)H]-DA) from human neocortex nerve terminals was studied in synaptosomes prepared from brain specimens removed in neurosurgery and exposed during superfusion to different releasing stimuli. Treatment with 15 mM KCl, 100 microM 4-aminopyridine, 1 microM ionomycin or 30 mM caffeine elicited almost identical overflows of tritium. Removal of external Ca(2+) ions abolished the overflow evoked by K(+) or ionomycin and largely prevented that caused by 4-aminopyridine; the overflow evoked by caffeine was completely independent of external Ca(2+). Exposure of synaptosomes to 25 microM of the broad spectrum calcium channel blocker CdCl(2) strongly inhibited the 4-aminopyridine-induced tritium overflow while that evoked by ionomycin remained unaffected. The Ca(2+) chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N' tetraacetic acid (BAPTA), reduced significantly the K(+)- and the caffeine-induced tritium overflow. The effect of caffeine was attenuated by exposure to the ryanodine receptor blocker dantrolene or when the membrane-impermeant inositol trisphosphate receptor antagonist, heparin, was entrapped into synaptosomes; the combined treatment with dantrolene and heparin abolished the release elicited by caffeine. Tetanus toxin, entrapped into human neocortex synaptosomes to avoid prolonged incubation, inhibited in a concentration-dependent manner the K(+)- or the 4-aminopyridine-evoked tritium overflow; in contrast, the release stimulated by ionomycin and by caffeine were both totally insensitive to the same concentrations of tetanus toxin. Western blot analysis showed about 50% reduction of the content of the vesicular protein, synaptobrevin, in synaptosomes poisoned with tetanus toxin. In conclusion, the release of dopamine from human neocortex nerve terminals can be triggered by Ca(2+) ions originating from various sources. It seems that stimuli not leading to activation of voltage-sensitive Ca(2+) channels elicit Ca(2+)-dependent, probably exocytotic, release that is insensitive to tetanus toxin.

Adult↗

Entrapping of impermeant probes of different size into nonpermeabilized synaptosomes as a method to study presynaptic mechanisms.

Small molecules present during brain tissue homogenization are known to be entrapped within subsequently isolated synaptosomes. We have revisited this technique in view of its systematic utilization to incorporate into nerve endings impermeant probes of large size. Rat neocortical synaptosomes were prepared in the absence or in the presence of each of the following compounds: 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), tetanus toxin (TeTx) or its light chain (TeTx-LC), pertussis toxin (PTx), anti-syntaxin, or anti-SNAP25 monoclonal antibodies. Release of endogenous GABA and glutamate was then evoked by high K+ depolarization. GABA and glutamate overflows were inhibited by entrapped BAPTA and in synaptosomes prepared by homogenization in the presence of varying concentrations of TeTx or TeTx-LC. When synaptobrevin cleavage in synaptosomes entrapped with TeTx was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by western blotting, the extent of proteolysis was found to correspond quantitatively to that of release inhibition. GABA and glutamate overflows were increased by entrapped PTx; moreover, (-)-baclofen inhibited amino acid overflow more potently in standard than in PTx-containing synaptosomes. The overflows of GABA and glutamate were similarly decreased following incorporation of anti-syntaxin or anti-SNAP25 antibodies. Synaptosomal entrapping may be routinely used to internalize membrane-impermeant agents of different size in studies of presynaptic mechanisms.

Animals↗

Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects.

In lysinuric protein intolerance (LPI), impaired transport of cationic amino acids in kidney and intestine is due to mutations of the SLC7A7 gene. To assess the functional consequences of the LPI defect in nonepithelial cells, we have characterized cationic amino acid (CAA) transport in human fibroblasts obtained from LPI patients and a normal subject. In both cell types the bidirectional fluxes of arginine are due to the additive contributions of two Na(+)-independent, transstimulated transport systems. One of these mechanisms, inhibited by N-ethylmaleimide (NEM) and sensitive to the membrane potential, is identifiable with system y(+). The NEM- and potential-insensitive component, suppressed by L-leucine only in the presence of Na(+), is mostly due to the activity of system y(+)L. The inward and outward activities of the two systems are comparable in control and LPI fibroblasts. Both cell types express SLC7A1 (CAT1) and SLC7A2 (CAT2B and CAT2A) as well as SLC7A6 (y+LAT2) and SLC7A7 (y+LAT1). We conclude that LPI fibroblasts exhibit normal CAA transport through system y(+)L, probably referable to the activity of SLC7A6/y+LAT2.

Adolescent↗

Attitudes and beliefs of palliative care physicians regarding communication with terminally ill cancer patients.

The subject of communication between palliative care physicians and their patients regarding their diagnosis and prognosis has not been extensively researched. The purpose of this survey was to compare the attitudes and beliefs of palliative care specialists regarding communication with the terminally ill in Europe, South America, and Canada. A sample of palliative care physicians from South America (Argentina and Brazil), French-speaking Europe, and Canada were identified, and posted a questionnaire. Physicians who stated that they practised palliative care at least 30% of their time were considered evaluable as palliative care specialists. Of a total of 272 questionnaires, 228 were returned (84%); and 182/228 (81%) respondents were considered to be palliative care specialists. Palliative care physicians in all three regions believed that cancer patients should be informed of their diagnosis and the terminal nature of their illness. Physicians reported that at least 60% of their patients knew their diagnosis and the terminal stage of their illness in 52% and 24% of cases in South America, and 69% and 38% of cases in Europe, respectively. All physicians agreed that 'do not resuscitate' orders should be present, and should be discussed with the patient in all cases. While 93% of Canadian physicians stated that at least 60% of their patients wanted to know about the terminal stage of their illness, only 18% of South American, and 26% of European physicians said this (P < 0.001). Similar results were found when the physicians were asked the percentage of families who want patients to know the terminal stage of their illness. However, almost all of the physicians agreed that if they had terminal cancer they would like to know. There was a significant association between patient based decision-making and female sex (P = 0.007), older age (P = 0.04), and physicians from Canada and South America (P < 0.001). Finally, in their daily decision making, South American physicians were significantly more likely to support beneficence and justice as compared with autonomy. Canadian physicians were more likely to support autonomy as compared with beneficence. In summary, our findings suggest that there are major regional differences in the attitudes and beliefs of physicians regarding communication at the end of life. More research is badly needed on the attitudes and beliefs of patients, families, and health care professionals in different regions of the world.

Attitude of Health Personnel↗