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Biomedical subjects

P Alvarez

Publications and source records attributed to P Alvarez.

At least 19 recordsLinked to original sources

Development of a system of indicators for sustainable port management.

The 1998 project ECOPORT, "Towards A Sustainable Transport Network", developed by the Valencia Port Authority (VPA), established the bases for implementing an Environmental Management System (EMS) in industrial harbours. The use of data and information shall always be required to develop an efficient EMS. The objective of the present research (INDAPORT) study is to propose a system of sustainable environmental management indicators to be used by any port authorities. All activities performed within a port area are analysed for any potential environmental impacts and risks. An environmental analysis of port activities has been carried out with the objective of designing the indicators system. Twenty-one corresponding activities have been identified for large industrial ports. Subsequently, the same methodology developed to date will be later applied to other Spanish and European ports. The study has been developed by using an original system and a methodology, which simultaneously use stage diagrams and systemic models (material and energy flow charts). Multi-criteria analysis techniques were used to evaluate potential impacts (identification of factors and evaluation of impacts).

Decision Support Techniques↗

Immune responses to the 105AD7 human anti-idiotypic vaccine after intensive chemotherapy, for osteosarcoma.

105AD7 is a human monoclonal antibody that mimics the complement regulatory protein, CD55, overexpressed by many solid tumours including osteosarcoma. This study was designed to assess the toxicity and efficacy of this vaccine in a young age group of patients within 1-6 months of myleosuppressive chemotherapy. Out of 28, 20 (71%, 95% CI 51-87%) patients showed a significant T-cell proliferation response in vitro to the 105AD7 protein but not to human IgG. Furthermore, 13 out of 22 (59%, 95% CI 36-79%) patients showed antigen-specific gammaIFN secretion (range 20-370 U/ml). Nine out of 28 (32%, 95% CI 16-52%) patients made weak antibody responses to CD55. This study showed that 105AD7 was well tolerated in younger patients with osteosarcoma. In addition, two patients with possible clinical responses were given compassionate permission to continue immunisation quarterly for 2 years. They both remain alive and disease free 5.8 and 6.5 years from original diagnosis of osteosarcoma and showed no adverse effects of repeated immunisation. In conclusion, the majority of patients showed measurable T helper responses when vaccination was commenced within a 6-month window of intensive chemotherapy with no clinically significant toxicity. Future clinical trials incorporating immune stimulation strategies should include early introduction of vaccines during the highest risk period for relapse.

Adult↗

Modulation of neuropeptide Y and norepinephrine on several leucocyte functions in adult, old and very old mice.

The age-related changes in the communication between the nervous and the immune system have been scarcely investigated, especially in very aged subjects. The present work deals with the in vitro effects of norepinephrine and neuropeptide Y, separately and jointly, on functions such as lymphoproliferation, NK activity, and IL-2 and TNF-alpha release of peritoneal leucocytes from adult (24+/-2 weeks), old (72+/-2 weeks) and very old (128+/-2 weeks) mice. The old mice showed a decrease in proliferation, NK activity and IL-2 release, and an increase in TNF-alpha, whereas in the very old mice these functions were more similar to those of the adults. The effects of neurotransmitters on these functions were different depending on the age of the animals.

Aging↗

Neural correlates of social odor recognition and the representation of individual distinctive social odors within entorhinal cortex and ventral subiculum.

Recognition of individual conspecifics is important for social behavior and requires the formation of memories for individually distinctive social signals. Individual recognition is often mediated by olfactory cues in mammals, especially nocturnal rodents such as golden hamsters. In hamsters, this form of recognition requires main olfactory system input to the lateral entorhinal cortex (LEnt). Here, we tested whether neurons in LEnt and the nearby ventral subiculum (VS) would show cellular correlates of this natural form of recognition memory. Two hundred ninety single neurons were recorded from both superficial (SE) and deep layers of LEnt (DE) and VS while male hamsters investigated volatile odorants from female vaginal secretions. Many neurons encoded differences between female's odors with many discriminating between odors from different individual females but not between different odor samples from the same female. Other neurons discriminated between odor samples from one female and generalized across collections from other females. LEnt and VS neurons showed enhanced or suppressed cellular activity during investigation of previously presented odors and in response to novel odors. A majority of SE neurons decreased firing to odor repetition and increased activity to novel odors. In contrast, DE neurons often showed suppressed activity in response to novel odors. Thus, neurons in LEnt and VS of male hamsters encode information that is critical for the identification and recognition of individual females by odor cues. This study reveals cellular mechanisms in LEnt and VS that may mediate a natural form of recognition memory in hamsters. These neuronal responses were similar to those observed in rats and monkeys during performance in standard recognition memory tasks. Consequently, the present data extend our understanding of the cellular basis for recognition memory and suggest that individual recognition requires similar neural mechanisms as those employed in laboratory tests of recognition memory.

Action Potentials↗

Host humoral immune response to Leishmania lipid-binding protein.

SUMMARY We report on the use of Leishmania donovani lipid-binding proteins (LBPs) as antigens capable of being recognized by serum from immunocompetent patients from southern Spain suffering from visceral leishmaniasis and from Peruvian patients with localized cutaneous leishmaniasis caused by Leishmania braziliensis. The absorbance found by immunoenzymatic techniques gave significantly different results for the serum samples from patients with and without leishmaniasis. Specificity by ELISA testing was 93.2% and sensibility 100%. Dot blots from human patient serum samples or naturally infected dogs from Spain gave similarly significant results. All the human serum samples from individuals with visceral leishmaniasis and the Leishmania-positive canine samples recognized two bands, with molecular weights of 8 and 57 kDa. The serum from individuals with cutaneous leishmaniasis caused by L. braziliensis recognized an additional band of 16 kDa. We discuss the role of Leishmania FABP and compare the immunological reactions found with serum samples from other protozoan infections such as toxoplasma and Chagas as well as bacterial infections such as tuberculosis and syphilis.

Adolescent↗

Improvement of the macrophage functions in prematurely ageing mice by a diet supplemented with thiolic antioxidants.

In a model of prematurely ageing mice, based on the different behavioral response in a simple T-maze test, we have studied in the present work the effect of a short-term (five-weeks) ingestion of thioproline (TP) plus n-acetylcysteine (NAC) (0.1% w/w of each antioxidant) on several functions of peritoneal macrophages from female Swiss mice. The antioxidant treatment increased the chemotaxis, phagocytosis and IL-1beta release and decreased the superoxide levels and TNFalpha production. These effects were more striking in macrophages from prematurely-ageing mice (PAM), than in those from the control group or non-prematurely-ageing mice (NPAM), bringing the above functions of the PAM to the NPAM levels. Diet supplementation with these thiolic compounds, namely TP and NAC, seems an effective therapy for protection against early immune decline in prematurely ageing mice.

Acetylcysteine↗

Changes with age in peritoneal macrophage functions. Implication of leukocytes in the oxidative stress of senescence.

The age-related deterioration of the immune cells contributes to the increased morbidity and mortality of the aged populations. Since ageing is the result of oxidative stress and macrophages are an important source of oxidation, which is produced in order to carry out many of their functions, the changes with age of several macrophage functions as well as of oxidative stress parameters (oxidants, inflammatory mediators and antioxidants) of peritoneal leukocytes have been investigated using young (4 months), adult (7 months), mature (12 months) and old (20 months) female ICR (CD-1) mice. With age the macrophage functions suffer deterioration. Thus, chemotaxis, phagocytosis and intracellular superoxide anion production decrease in old animals. Moreover, the levels of antioxidant defenses, such as superoxide dismutase activity, decrease with ageing. However, the adherence capacity and the release of oxidant and inflammatory mediators, such as extracellular superoxide anion, TNF-alpha and PGE2, as well as oxidized glutathione/ reduced glutathione ratio, increase with age. These results show that these cells suffer oxidative stress with ageing, which results in an increase of the oxidative damage to nuclear DNA. These changes in peritoneal immune cells could contribute to the chronic oxidative stress state linked to senescence.

Animals↗

Incarcerated groin hernias in adults: presentation and outcome.

Despite universal acceptance of the value of elective hernia repair, many patients present with incarceration or strangulation, which are associated with significant morbidity and mortality. We reviewed 147 patients who underwent emergency surgery for incarcerated groin hernias during a 10-year period in order to analyze the presentation and outcome in our practice. Median age of the patients was 70 years. There were 77 men and 70 women. Femoral hernias were seen in 77 patients and inguinal hernias in 70. Coexisting diseases were found in 82 cases (55.8%). Bowel resection was required in 19 patients (12.9%). The overall and major morbidity rates were 41.5% and 9.6%, respectively. The mortality rate was 3.4%. Longer duration of symptoms, late hospitalization, concomitant diseases, and high ASA class were found to be significant factors linked with unfavorable outcomes. Because of high morbidity and mortality associated with incarceration, elective repair of groin hernias should be done whenever possible.

Adult↗

Influence of autograft removal on rabbit patellar tendon length.

Twelve adult New Zealand white rabbits were randomly divided into two groups. In group 1, 30% of the central mass of the right patellar tendon was removed. In group 2, 60% was removed. The left knees served as controls. The animals were killed 1 year later. The patella-patellar tendon-tibial tuberosity units of all knees were studied using histological and morphometric analysis. In both groups, the tendons had lengthened. Lengthening average was 2.50 mm in group 1 and 8.17 mm in group 2. In both groups, histology revealed poor alignment of the collagen fibres and high cellularity, although the findings in group 1 were nearer the normal histological pattern. The results suggest that removal of significant portions of the patellar tendon leads to lengthening of the resulting tendon. In clinical practice, it seems prudent to pay attention to the dimensions of the patellar tendon when harvesting a graft.

Animals↗

Antinociceptive effect of clomipramine in monoarthritic rats as revealed by the paw pressure test and the C-fiber-evoked reflex.

The antinociceptive effect of clomipramine was studied in monoarthritic rats by using the paw pressure test and the C-fiber-evoked reflex. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. Joint circumference as well as vocalization threshold to graded paw pressure were evaluated weekly during a 14-week period after the intra-articular injection. At week 8, monoarthritic and vehicle-injected control rats were given either clomipramine or saline and both the paw pressure threshold and inhibition of the C-fiber-evoked reflex response were evaluated. Results showed that (i) 1.5, 3.0, and 6.0 mg/kg, i.v. of clomipramine induced significantly greater dose-dependent antinociception to paw pressure testing in the monoarthritic group, as compared to the control one; and (ii) 0.75, 1.5, 3.0, and 6.0 mg/kg, i.v. of clomipramine exerted significantly higher dose-dependent inhibition of the C-reflex activity in monoarthritic rats than in controls. Results suggest that the higher sensitivity to clomipramine in monoarthritic rats could be related to adaptive changes occurring in monoamine metabolism or in other neurotransmitter systems during chronic pain.

Analgesics↗

Homogenous catalyzed ozonation of simazine. Effect of Mn(II) and Fe(II).

Simazine, [2-chloro, 4,6-bis(ethylamino)-1,3,5-s-triazine], a common herbicide typically found in surface and ground water was ozonised by using catalytic amounts of Mn(II) and Fe(II). An optimum value for metal concentration was found in the process. Some inhibition of the simazine degradation rate was observed when these metals were added above the optimum concentration. The pH of the reaction media played a significant role in the simazine oxidation rate. Thus, an increase in simazine conversion was observed when the pH was raised from 5 to 9. However, the catalytic effect of added manganese was negligible at the highest pH used in this study (pH 9). The beneficial influence of Fe(II) was also observed when utilising the combination of ozone and hydrogen peroxide. Contrarily, Mn(II) presented a negative influence on simazine conversion when using this oxidation technology.

Catalysis↗

Multiple overlapping epitopes in the repetitive unit of the shed acute-phase antigen from Trypanosoma cruzi enhance its immunogenic properties.

The repetitive shed acute-phase antigen (SAPA) from Trypanosoma cruzi was thoroughly mapped by SPOT peptides and phage display strategies, showing that a single SAPA repeat is composed of multiple overlapping B-cell epitopes. We propose that this intricate antigenic structure constitutes an alternative device to repetitiveness in order to improve its immunogenicity.

Animals↗

Epitope mapping of trans-sialidase from Trypanosoma cruzi reveals the presence of several cross-reactive determinants.

Trypanosoma cruzi, the agent of Chagas' disease, expresses trans-sialidase, a unique enzyme activity that enables the parasite to invade host cells by transferring sialyl residues from host glyconjugates to the parasite's surface acceptor molecules. The enzyme is also shed into the surrounding environment, causing apoptosis in cells from the immune system. During infections, an antibody response against the catalytic region of the trans-sialidase that is coincident with the control of the parasitemia and survival of the host is observed. This low-titer humoral response is characterized by its persistence for many years in benznidazole-treated patients. Here we analyzed the antigenic structure of the molecule by phage-displayed peptide combinatorial libraries and SPOT synthesis. Several epitopes were defined and located on the three-dimensional model of the enzyme. Unexpectedly, cross-reaction was found among several epitopes distributed in different locations displaying nonconsensus sequences. This finding was confirmed by the reactivity of three monoclonal antibodies able to recognize non-sequence-related peptides that together constitute the surface surrounding the catalytic site of the enzyme. The presence of cross-reacting epitopes within a single molecule suggests a mechanism developed to avoid a strong humoral response by displaying an undefined target to the immune system.

Amino Acid Sequence↗

Effects of intraovarian infusion of insulin-like growth factor-I on ovarian follicular function in cattle.

The objective of this study was to determine if increased secretion of intraovarian insulin-like growth factor-I (IGF-I), experimentally induced via minipumps, affects follicular function in cattle. Fourteen cycling Holstein cows were divided equally into two groups: Control, osmotic minipumps (containing vehicle) surgically inserted into each ovary, or IGF-I treated, osmotic minipumps as in Controls but pumping 2.0 microg of recombinant human IGF-I per hr for 7 days. All cows were synchronized with prostaglandin F(2alpha) 0.10) between Control and IGF-I-treated cows during Days 2 to 6 of treatment. IGF-I treatment increased (P<0.05) estradiol concentrations in follicular fluid of small follicles, but had no effect (P<0.10) on estradiol concentrations in follicular fluid of large follicles, or on progesterone, androstenedione, or IGF binding protein concentrations in small or large follicles. We conclude that a 7-day infusion of IGF-I directly into the stroma of the ovary altered follicular growth and follicular fluid estradiol concentrations.

Animals↗

Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats.

Brain tumors are often incurable despite current aggressive treatment modalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h-R3 is a humanized antiepidermal growth factor receptor Mab that successfully targets the epidermal growth factor receptor, which is overexpressed in glioblastomas. We studied the acute local and systemic toxicity effects of intraventricular 188Re-h-R3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5 -microl dose (2.5 microl into the left and 2.5 microl into the right lateral ventricles) of neutral solution containing 50 microg of h- R3 labeled with 49.5 +/- 1.7,284 +/- 13.7 or 579 +/- 23.7 muCi of 188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Body weights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out after completion of the study. All animals, but one, remained clinically stable. Toxicities included local radionecrosis, discrete increase in ALAT and creatinine blood values at higher dose level. We concluded that a single intraventricular administration of relatively large doses of 188Re-h-R3 is tolerable and causes minimal local and systemic toxicity effects in rats. Nevertheless, further studies are necessary to discard learning and behavioral problems.

Adenocarcinoma↗

Ovarian and endocrine characteristics during an estrous cycle in Angus, Brahman, and Senepol cows in a subtropical environment.

To determine breed differences in ovarian function and endocrine secretion, daily rectal ultrasonography was conducted on multiparous lactating Angus (temperate Bos taurus; n = 12), Brahman (tropical Bos indicus; n = 12), and Senepol (tropical Bos taurus; n = 12) cows during an estrous cycle in summer. Blood was collected daily to quantify plasma concentrations of FSH, LH, progesterone, estradiol, GH, insulin-like growth factor (IGF)-I, IGF-II, IGF binding proteins (IGFBP), insulin, glucose, and plasma urea nitrogen (PUN). Numbers of small (2 to 5 mm), medium (6 to 8 mm), and large follicles (> or = 9 mm) were greater (P < .05) in Brahman than in Angus and(or) Senepol cows. Length of the estrous cycle (SEM = .6 d) was similar (P > .10) among Senepol (20.4 d), Angus (19.5 d), and Brahman (19.7 d) cows. Senepol cows had greater (P < .05) diameters of the corpus luteum (CL) and a delayed regression of the CL as compared with Angus cows. The secondary surge of FSH (between d 1 and 2; d 0 = estrus) was greater in Angus than Brahman or Senepol cows (breed x day, P < .05). Between d 2 and 14 of the estrous cycle, concentrations of progesterone, LH, IGF-II, and binding activities of IGFBP-3, IGFBP-2, and the 27- to 29-kDa IGFBP in plasma did not differ (P > .10) among breeds. Concentrations of GH, IGF-I, insulin, and PUN were greater (P < .001) and binding activities of the 22-kDa and 20-kDa IGFBP tended (P < .10) to be greater in plasma of Brahman than in Angus or Senepol cows. Plasma glucose concentrations were greater (P < .05) in Senepol than in Brahman or Angus cows. In conclusion, Brahman (Bos indicus) and Senepol cows (tropical Bos taurus) had greater numbers of follicles in all size categories and greater diameter of CL than Angus (temperate Bos taurus) cows. These ovarian differences may be due to changes in the pattern of secretion of FSH, insulin, IGF-I, and GH but not LH, IGF-II, or IGFBP-2 or -3.

Animals↗