Niveles de anticuerpos anti nucleares por Fana y Ana-Lia en pacientes con enfermedades reumáticas sistémicas / Levels of anti-nuclear antibodies by Fana and Ana-Lia in systemic rheumatic diseases patients

Objetivo: Correlacionar los niveles de anticuerpos antinucleares obtenidos por las técnicas de inmunofluorescencia indirecta (FANA) e inmunoensayo lineal (ANA-LIA) en pacientes diagnosticados o con sospecha clínica de enfermedad autoinmune. Métodos: Se incluyeron 100 pacientes que dieron su consentimiento informado para participar en el estudio. Los ensayos e interpretación de los resultados de las pruebas de FANA y ANA-LIA se realizaron siguiendo las recomendaciones del fabricante. Resultados: el 97,4% de los pacientes estudiados eran de sexo femenino con edad promedio de 42 años, siendo la Artritis reumatoide, Poliartritis y Lupus Eritematoso Sistémico las enfermedades que con mayor frecuencia acompañaron la solicitud médica. Se observó que ambos métodos fueron positivos en el 21% de los casos y que el indice de correlaciòn de Kappa entre las pruebas fue moderado (k= 0,51; p< 0,05), la sensibilidad y especificidad de los métodos fue del 71,4% y 84,8% respectivamente, se observó también que para un determinado patrón fluorescente puede haber positividad de más de un antígeno de la prueba de ANA-LIA y viceversa. Conclusiones: FANA es el método de tamizaje aceptado en la práctica clínica para orientar hacia un diagnóstico clínico de enfermedad autoinmune más probable, debido a la subjetividad en la interpretación de sus resultados y necesidad de entrenamiento en la identificación de los patrones fluorescentes, se requiere del apoyo de otros métodos de laboratorio que permitan identificar con mayor precisión los antígenos reconocidos por los autoanticuerpos, ANA-LIA es una herramienta de laboratorio costo-efectiva de elevada sensibilidad y especificidad que se ajusta a este requerimiento.

Objective: To correlate levels of antinuclear antibodies obtained by indirect immunofluorescence techniques (FANA) and linear immunoassay (ANA-LIA) in patients diagnosed or with clinical suspicion of autoimmune disease. Methods: 100 patients who gave their informed consent to participate in the study were included. Assays and interpretation of results of FANA and ANA-LIA test were performed following the manufacturer's recommendations. Results: 97,4% of the patients studied were female with an average age of 42 years, being rheumatoid arthritis, polyarthritis and systemic lupus erythematosus the diseases that most frequently accompanied the medical request. It was observed that both methods were positive in 21% of the cases and that the Kappa correlation index was moderate between the tests (k = 0,51; p <0,05), the sensitivity and specificity of the methods was 71,4% and 84,8% respectively. It was also observed that for a given fluorescent pattern there may be positivity of more than one antigen of the ANA-LIA test and vice versa. Conclusions: FANA is the screening method accepted in the clinical practice to guide towards a more probable clinical diagnosis of autoimmune disease. Due to the subjectivity in the interpretation of its results and the need for training in the identification of fluorescent patterns, the support of other laboratory methods that allow the identification of antigens recognized by autoantibodies with greater precision is necessary, ANA-LIA is a cost-effective laboratory tool of high sensitivity and specificity that meets this requirement.

The C-shaped canal molar: an Endodontic-Archaeological study of the relationships between Mayan pre-Hispanic and contemporary population of Yucatán.

AIM: To assess the prevalence of C-shaped canal systems in mandibular second molars, in samples of modern and pre-Hispanic Mayan individuals in Yucatán, Mexico, and to analyse the trait through time and attempt to find new evidence of ethnical bonds between populations. METHODOLOGY: Three hundred and forty-one randomly selected patients were treated in the Endodontic Clinic at the Dental school of the Universidad Autónoma de Yucatán, and 48 mandibular second molars from pre-Hispanic Mayan collections were macroscopically and radiographically inspected. Statistical analysis was performed with a Fisher's exact test to compare the prevalence of C-shaped canal systems in modern and archaeological samples. RESULTS: In the clinical observation, 118 of 341 (35%) patients treated endodontically had C-shaped mandibular second molars. In the radiographical evaluation, 17 of 48 (35%) archaeological molars had fused roots and pulp chamber morphology categorized as C-shaped. There were no significant differences between the frequencies in both samples. CONCLUSION: This study highlighted that a one-rooted mandibular molar was likely to have a C-shaped canal. The similarity between ancient and modern samples indicates that the genetic make-up since the European conquest has not affected the expression of this trait. This study supports the theory that the Mayan population has a relationship with the Northeast Asian population.

Emergence of ageing-related changes in insulin secretion by pancreatic islets of male rat offspring of mothers fed a low-protein diet.

Maternal low-protein (LP) diets programme ß-cell secretion, potentially altering the emergence of ageing of offspring pancreatic function. We hypothesised that isolated pancreatic islet ß-cell secretory responses are blunted in offspring exposed to LP during development and age-related reduction is influenced by the developmental stage of exposure to decreased nutrition. We studied male offspring of rats fed control (C) or LP protein (R) diets in pregnancy, first letter and/or lactation second letter of CC, RR, CR or RC groups. Serum glucose, insulin and homeostatic model assessment (HOMA) were measured. Pancreatic islets were isolated and in vitro insulin secretion quantified in low (LG - 5 mM) or high glucose (HG - 11 mM). Body weight and serum values between groups were similar at all ages. Insulin and HOMA rose with age and were highest at postnatal day (PND) 450 in all groups. At PND 36, insulin secretion was greatest in RR and RC. Only CC increased insulin secretion to HG. By PND 110, restricted groups responded less to LG but increased secretion to HG. By PND 450, CC offspring alone increased secretion to HG. Despite minimal differences in circulating insulin and glucose, reduced maternal protein intake affected insulin secretion at all ages. In addition, ageing reduced function in all R groups compared with CC by PND 110 and further by PND 450 most markedly in RC. We conclude that maternal LP diet during pregnancy and/or lactation impairs offspring insulin secretory response to a glucose challenge and alters the trajectory of ageing of pancreatic insulin secretion.

Developmental programming of aging of isolated pancreatic islet glucose-stimulated insulin secretion in female offspring of mothers fed low-protein diets in pregnancy and/or lactation.

Diabetes predisposition is determined by pancreatic islet insulin secretion and insulin resistance. We studied female rat offspring exposed to low-protein maternal diet (50% control protein diet) in pregnancy and/or lactation at postnatal days 36, 110 and 450. Rats were fed either control 20% casein diet (C) or restricted diet (R - 10% casein) during pregnancy. After delivery, mothers received either C or R diet until weaning to provide four offspring groups: CC, RR, CR and RC (first letter denoting maternal pregnancy diet and the second lactation diet). Serum glucose, insulin and homeostatic model assessment (HOMA) were measured. Pancreatic islets were isolated and in vitro insulin secretion quantified in low glucose (5 mM) and high glucose (11 mM). Serum glucose, insulin and HOMA were similar in all groups at 36 and 110 postnatal days. HOMA was only higher in RR at 450 postnatal days. Only CC demonstrated differences in glucose sensitivity of ß-cells to high and low doses at the three ages studied. At 36 days, RR, CR and RC and at 450 days RR and RC groups did not show glucose-stimulated insulin secretion differences between low and high glucose. Aging-associated glucose-stimulated insulin secretion loss was affected by maternal dietary history, indicating that developmental programming must be considered a major factor in aging-related development of predisposition to later-life dysfunctional insulin metabolism. Female offspring islets' insulin secretion was higher than previously reported in males.

Linear enamel hypoplasia at Xcambó, Yucatán, during the Maya Classic period: An evaluation of coastal marshland impact on ancient human populations.

Non-specific stress markers such as linear enamel hypoplasia (LEH) have been associated in the literature with a large number of possible conditions disrupting the individual's homeostasis, though metabolic strain originating synergistically by disease and malnutrition has been held to be the main cause behind enamel disruption. The analysis of LEH in the Maya Classic period site of Xcambó, located along the northern coast of the Yucatán peninsula, reveals high exposure to stressful conditions during infancy regardless of age and sex. Yet, the inhabitants of the site were of a medium to high social and economic status, with access to balanced and protein-rich nutritional resources, which should have functioned as a cultural buffer to the impact of stress. In the light of this apparent contradiction, this paper discusses the impact of environmental conditions on the record of metabolic stress. Our conclusions pose a cautionary caveat for inferring nutrition and status in ancient pre-antibiotic populations solely from the occurrence of linear enamel hypoplasia.

Intersectoral coordination in Aedes aegypti control. A pilot project in Havana City, Cuba.

UNLABELLED: Background The 55th World Health Assembly declared dengue prevention and control a priority and urged Member States to develop sustainable intersectoral strategies to this end. To provide evidence for the reorientation of the dengue prevention policy in Cuba, we launched an intervention study to document the effectiveness of a local-level intersectoral approach. METHODS: We used a quasi-experimental design. Social scientists introduced participatory methods to facilitate dialogue in the biweekly meetings of the intersectoral Health Council of the intervention area. This council subsequently developed an intersectoral plan for dengue prevention, of which the core objective was to design and implement activities for communication and social mobilization. In the control area, routine dengue control activities continued without additional input. Knowledge, attitudes and perceptions of dengue, and entomological indices were compared inside and between the areas before and after the 1-year intervention period. RESULTS: In the intervention area the Health Council elaborated an intersectoral plan for dengue prevention focused on source reduction. The Aedes aegypti control methods consisted in eliminating useless containers in the houses and surroundings, covering tanks, and cleaning public and inhabited areas. It was implemented through communication and social mobilization. The Health Council in the control area occasionally discussed dengue issues but did not develop a coordinated action plan. Good knowledge about breeding sites and disease symptoms increased significantly (by 49.7% and 17.1% respectively) in the intervention area as well as the proportion of respondents eliminating containers in and around their houses (by 44%). No changes were observed in the control area. The House Index in the intervention area was 3.72% at baseline and decreased to 0.61% after 1 year. In the control area it remained stable throughout the study period (1.31% and 1.65% respectively). CONCLUSION: The introduction of a participatory approach by social scientists promotes changes in intersectoral management. This facilitates social mobilization which, in its turn, leads to significant changes in knowledge, attitudes and dengue-related practices in the population and eventually to more effective control of Ae. aegypti.

1Intersectoral coordination in Aedes aegypti control: a pilot project in Havana City, Cuba

Summary: Background The 55th World Health Assembly declared dengue prevention and control a priority and urged Member States to develop sustainable intersectoral strategies to this end. To provide evidence for the reorientation of the dengue prevention policy in Cuba, we launched an intervention study to document the effectiveness of a local-level intersectoral approach. METHODS: We used a quasi-experimental design. Social scientists introduced participatory methods to facilitate dialogue in the biweekly meetings of the intersectoral Health Council of the intervention area. This council subsequently developed an intersectoral plan for dengue prevention, of which the core objective was to design and implement activities for communication and social mobilization. In the control area, routine dengue control activities continued without additional input. Knowledge, attitudes and perceptions of dengue, and entomological indices were compared inside and between the areas before and after the 1-year intervention period. RESULTS: In the intervention area the Health Council elaborated an intersectoral plan for dengue prevention focused on source reduction. The Aedes aegypti control methods consisted in eliminating useless containers in the houses and surroundings, covering tanks, and cleaning public and inhabited areas. It was implemented through communication and social mobilization. The Health Council in the control area occasionally discussed dengue issues but did not develop a coordinated action plan. Good knowledge about breeding sites and disease symptoms increased significantly (by 49.7percent and 17.1percent respectively) in the intervention area as well as the proportion of respondents eliminating containers in and around their houses (by 44Percent). No changes were observed in the control area. The House Index in the intervention area was 3.72 percent at baseline and decreased to 0.61percent after 1 year.........(AU)

Resumen: Antecedentes La 55a Asamblea Mundial de la Salud declaró la prevención del dengue y el control en una prioridad e instó a los Estados Miembros a desarrollar estrategias intersectoriales con este fin. Que presentaran pruebas para la reorientación de la política de prevención del dengue en Cuba, hemos lanzado un estudio de intervención para documentar la eficacia de un local intersectorial. MÉTODOS: Se utilizó un diseño cuasi-experimental. Los científicos sociales presentó los métodos participativos para facilitar el diálogo en las reuniones quincenales del Consejo Intersectorial de Salud de la zona de intervención. Este consejo posteriormente desarrollado un plan intersectorial para la prevención del dengue, de los cuales el principal objetivo era diseñar y ejecutar actividades de comunicación y movilización social. En la zona de control, las actividades rutinarias de control del dengue siguió sin aportaciones adicionales. Conocimientos, actitudes y percepciones del dengue, y se compararon los índices entomológicos dentro y entre las zonas antes y después del 1 año de período de intervención. RESULTADOS: En el área de intervención del Consejo de Salud elaboró un plan intersectorial para la prevención del dengue se centró en la reducción de las fuentes. Los métodos de control de Aedes aegypti consiste en la eliminación de recipientes inservibles en las casas y sus alrededores, que abarca los tanques, y la limpieza pública y las zonas habitadas. Se aplicó a través de la comunicación y la movilización social. El Consejo de Salud en la zona de control del dengue a veces discutido, pero no cuestiones de desarrollar un plan de acción coordinado................

Validación de métodos serológicos que se emplean para el diagnóstico de enfermedades reumáticas definidas: Lupus erimatoso sitémico (LES) / Validation of methods serológicos that are used for the diagnosis of defined rheumatic illnesses: Lupus erimatoso sitémico

En el presente trabajo se aplicó un método estadístico no convencional para validar los substratos empleados para detectar anticuerpos antinucleares por inmunofluorescencia indirecta (FANA), comparado con la preuba confirmatoria de ELISA indirecto que mide Anticuerpos anti-dsDNA. Se determinó que los substratos: (línea celular BHK_21 y cortes criostáticos de higado o riñon de rata Ratus novergicus) tenían la misma sensibilidad y valor predictivo negativo (100 por ciento) La línea celular BHK-21 demostró tener mayor especificidad 69 por ciento, valor predictivo positivo 75,8 por ciento, eficiencia 84,3 por ciento y concordancia con los resultados emitidos por la técnica de ELISA (0,81) "muy buena" según el índice de KAppa. Se encontró que el patrón fluorescente difuso a título 1/32 está presente sistemáticamente en todas las muestras tanto positivas comonegativas para anti-ds-DNA. Se demostró que utilizar la línea celular BHK-21 (que reemplaza a la línea tradicional Hep-2), como sustrato "FANA", resulta ser el método taniz, mas eficiente, sensible, específico y de mayor concordancia con los resultados emitidos por un método confirmado para LES, que mide anti-ds-DNA.

Inhibition of mouth skeletal muscle relaxation by flavonoids of Cistus ladanifer L.: a plant defense mechanism against herbivores.

Cistus ladanifer exudate is a potent inhibitor of the sarcoplasmic reticulum Ca2+-ATPase (Ca2+-pump) of rabbit skeletal muscle, a well-established model for active transport that plays a leading role in skeletal muscle relaxation. The low concentration of exudate needed to produce 50% of the maximum inhibition of the sarcoplasmic reticulum Ca2+-ATPase activity, 40-60 microg/ml, suggests that eating only a few milligrams of C. ladanifer leaves can impair the relaxation of the mouth skeletal muscle of herbivores, as the exudate reaches up to 140 mg/g of dry leaves in summer season. The flavonoid fraction of the exudate accounts fully for the functional impairment of the sarcoplasmic reticulum produced by the exudate (up to a dose of 250-300 microg/ml). The flavonoids present in this exudate impair the skeletal muscle sarcoplasmic reticulum function at two different levels: (i) by inhibition of the Ca2+-ATPase activity, and (ii) by decreasing the steady state ATP-dependent Ca2+-accumulation. Among the exudate flavonoids, apigenin and 3,7-di-O-methyl kaempferol are the most potent inhibitors of the skeletal muscle sarcoplasmic reticulum. We conclude that the flavonoids of this exudate can elicit an avoidance reaction of the herbivores eating C. ladanifer leaves through impairment of mouth skeletal muscle relaxation.

[Prevalence of sexually transmitted diseases and the use of the condom among sex workers]. / Prevalencia de enfermedades de transmisión sexual y uso del condón en sexoservidoras.

OBJECTIVE: To determine the prevalence of sexually transmitted diseases (STD) and the use of condoms by sex workers, assisted in a health module. MATERIAL AND METHODS: A cross sectional study, was performed with prostitutes in Coatzacoalcos, Veracruz through a self-administered questionnaire in a period from January 3 to February 9, 2001. The questionnaire evaluated gynecology-obstetric background, STD and the use of condoms. Clinical records and laboratory tests were evaluated for STD screening. RESULTS: A total number of 196 sex workers from 71 work places were evaluated. The average age was 29.5 +/- 3.3 years. One hundred and eleven (57%) reported being single. 189 (96.4%) presented at least a case of vaginosis during the year 2000 and 148 (75.5%) were diagnosed having vulvovaginitis due to fungus. Syphilis was identified in 4 (2%) cases and (0.5%) acquired immune deficiency syndrome. 45 (23%) reported they always use a condom and 113 (58%) use condoms very often. CONCLUSIONS: There is a high prevalence of vulva and vagina disorders, as well as syphilis. High rates of sex workers use condoms.

Plant growth inhibiting flavonoids in exudate of Cistus ladanifer and in associated soils.

Of the aglycone flavonoids identified in the exudate of cistus ladanifer, two, the flavone apigenin-4'-(O)-methyl and the flavonol kaempferol-3,7-di(O)-methyl inhibit development of the seedlings of Rumex crispus at 0.5 and 1 mM. Additive effects were observed between the major flavonols of the exudate kaempferol-3-(O)-methyl and kaempferol-3,7-di-(O)-methyl in inhibiting the size of the cotyledons and delaying the germination and cotyledon emergence. The presence of apigenin-4'-(O)-methyl, kaempferol-3,7-di-(O)-methyl, and kaempferol-3-(O)-methyl was detected in the soils associated with C. ladanifer during the summer and autumn months. That these compounds are present in the soil and are not restricted to the leaves provides support for the hypothesis that C. ladanifer has allelopathic potential.

Identification and effects of interaction phytotoxic compounds from exudate of Cistus ladanifer leaves.

Eleven allelochemicals (ferulic acid, cinnamic acid, 4-hydroxybenzoic acid, hydroxycinnamic acid, methyl propionate, oxalic acid, methylmalonic acid, p-anisic acid, butyric acid, 3-hydroxybutyric acid, and azulene) were identified in the exudate of Cistus ladanifer L. We studied the effect of each on germination, cotyledon emergence, root length, and cotyledon length of Rumex crispus. Three groups were distinguished with respect to phytotoxic activity: compounds with low activity (ferulic acid, 4-hydroxybenzoic acid, oxalic acid, methylmalonic acid, p-anisic acid, hydroxybutyric acid, and azulene), with intermediate activity (cinnamic acid and hydroxycinnamic acid), and with high activity (methyl propionate and butyric acid). The effect of the interaction of the compounds was studied. When acting conjointly, all combinations tested produced a more negative effect on both germination and seedling growth than when acting alone. The interaction affected cotyledon emergence and root length more negatively than germination and cotyledon length. When hydroxycinnamic acid and cinnamic acid were added to these mixtures there was an enhancement in the phytotoxic activity, accentuating the effect of the other allelochemicals.

Fibrin glue-antibiotic mixture in the treatment of anal fistulae: experience with 69 cases.

BACKGROUND/AIMS: To investigate the potential value of the use of the fibrin glue-antibiotic mixture in the treatment of anal fistulae. MATERIALS AND METHODS: This study included 69 patients with idiopathic nonspecific anal fistulae. Patients with IBD (inflammatory bowel disease), TBC, actinomycosis, and cancer were excluded from the study. The microbiological analysis of the discharge of the fistula was done routinely. If there was any doubt about vertical classification of the fistulous tract MR of anal canal was necessary. As regards the vertical disposition, 39 fistulae were classified as intersphincteric and 30 as transsphincteric, and as to the length of the fistulous tract, 24 fistulas had tracts 3.5 cm long. All fistulae were first treated with the lavage of the fistulous tract with antibiotic solution until a sterile microbiological finding was obtained. This was followed by electrocoagulation of the fistulous tract with a special probe for the eradication of granulomatous tissue. Finally the fibrin glue-antibiotic mixture (Tisseel, Immuno Ltd., Vienna, Austria) was applied. RESULTS: After a follow-up of 18-36 months (median 28) 18 patients (26%) had a recurrence; among these, intersphincteric fistula recurred in 9 patients (23%) and transsphincteric also in 9 (30%). Regarding the length of the fistulous tract, a fistula with a 3.5 cm long tract in 5 (11%). CONCLUSION: The analysis showed that the success of the treatment of anal fistulae with fibrin glue-antibiotic mixture was independent of the vertical disposition of the fistula, and was dependent on the length of the fistulous tract. Surgical treatment remains a golden standard for simple fistulae with a tract

Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate.

At high fluence rates in animal models, photodynamic therapy (PDT) can photochemically deplete ambient tumor oxygen through the generation of singlet oxygen, causing acute hypoxia and limiting treatment effectiveness. We report that standard clinical treatment conditions (1 mg/kg Photofrin, light at 630 nm and 150 mW/cm2), which are highly effective for treating human basal cell carcinomas, significantly diminished tumor oxygen levels during initial light delivery in a majority of carcinomas. Oxygen depletion could be found during at least 40% of the total light dose, but tumors appeared well oxygenated toward the end of treatment. In contrast, initial light delivery at a lower fluence rate of 30 mW/cm2 increased tumor oxygenation in a majority of carcinomas. Laser treatment caused an intensity- and treatment time-dependent increase in tumor temperature. The data suggest that high fluence rate treatment, although effective, may be inefficient.

Percutaneous autologous bone marrow grafting on the site of tibial delayed union.

Six months after injury, 150 mL of autogenous bone marrow was applied percutaneously at the site of delayed union to stimulate the healing of a tibial delayed union fracture in a 44 year-old man. Five months following the procedure, the fracture gaps and bone defects were completely filled with callus, the external fixator was removed, and the patient started using normal leg loading.

Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.

Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also following other pentadecapeptide BPC-157 regimens (local application, or intermittent intramuscular administration), the number of animals with healed defect was increased. Hopefully, in the light of the suggested stomach significance for bone homeostasis, the possible relevance of this pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of unwanted effects) could be a basis for methods of choice in the future management of healing impairment in humans, and requires further investigation.

New model of cytoprotection/adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin.

Adaptive cytoprotection in the stomach was originally defined by applying the exogenous irritants only. The contribution of endogenous irritants as inductors of initial lesions was not specially evaluated. No attempt was made to either focus antiulcer agent activity on adaptive cytoprotection, or split their 'cytoprotection' into complex adaptive cytoprotective activity and simple cytoprotective effects. Agents had so far not been applied simultaneously with the second challenge with ethanol (or irritant), when differences between cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for 24 h in rats was introduced as new model for analyzing cytoprotection/adaptive cytoprotection. The contribution of the up-normal level of endogenous irritants and the endogenous small irritant-induced minor lesions during the adaptive cytoprotection were studied. The effect of late challenge with 96% ethanol in the presence of an up-normal level of endogenous irritants and endogenous small irritant-induced minor lesions was compared with results of classic studies of ethanol-induced gastric lesions in normal rats (1 ml/rat i.g.). Antiulcer agents or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic studies, were given at several points during injury induction: (i) surgery, (ii) mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable period following either mild ethanol or surgery). Their effects were compared in rats treated as follows: exogenous irritant studies (96% or 20% ethanol), exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol), endogenous irritant studies (gastrojejunal anastomosis for 24 h), and endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before 96% ethanol). Characteristic of the various irritants differed: the (preceding) small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous irritant studies) vs. endogenous (e.g., (increased) gastric acid secretion, duodenal reflux in gastric content in rats with termino-lateral gastrojejunal anastomosis) (endogenous irritant studies)). These factors caused modifications of agents' activities not, as initially thought, giving simple 'cytoprotection', but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had only cytoprotective activity (exogenous irritant-studies), whereas pentadecapeptide BPC157 (10 microg or 10 ng), and omeprazole (10 mg) had mainly adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both cytoprotective and adaptive cytoprotective activities (exogenous/exogenous irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.), showed that only events preceding the late challenge with ethanol may be prostaglandin-dependent in both models. The second, adaptive cytoprotective part, seen after late ethanol challenge, may be either prostaglandin-dependent (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous irritant studies). Both spontaneous lesion reduction, as an essential mechanism of adaptive cytoprotection, and the further lesion reduction by agents, such as pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as an essential link between the various reactions in cytoprotection/adaptive cytoprotection.

Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.

Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulcer agents, called 'direct cytoprotection', was evidenced in totally gastrectomized rats duodenum challenged with cysteamine 24 h after surgery, and sacrificed 24 h after ulcerogen application. The further focus was on the possibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopically (percentage of ulcerations areas) and microscopically (percentage of areas of ulcers, regeneration and hyperplasia; number of inflammatory cells - polymorphonuclear and mononuclear). Starting 24 h after surgery, the medication was continuously given in the drinking water, in a volume of 12.5 mL/rat daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC 157 125 mg or 125 ng, cholestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL x kg(-1) water. In support of these initial findings, and considering gastrectomized acid-free rats as an ideal model for long-term cytoprotective studies as well, pentadecapeptide BPC 157 markedly attenuated termino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti-ulcer agents. After 1-week-old oesophagitis (microscopical assessment), but not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ranitidine or sucralfate compared to controls. Similar effectiveness was noted for cholestyramine. The obtained results were supported also by inflammatory cell assessment. Compared with control values, BPC 157-treated groups consistently presented less polymorphonuclears and less mononuclears in all assessed periods. Interestingly, the values obtained in other treated groups showed no difference compared with control values. Thus, despite limitations, a generalization supporting a direct importance of a common cytoprotective approach, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157 rats, than in reference agents, ranitidine, sucralfate, as well as cholestyramine) may be a likely suitable therapy in otherwise resistant reflux oesophagitis conditions.

[Surgical treatment of war injuries of the veins]. / Kirursko lijecenje ratnih ozljeda vena.

Between April 1991 and December 1995, 118 patients were treated for wartime venous injuries. There were 108 (91.5%) venous injuries combined with arterial ones, and 52 (49%) with bone fractures. A total of 85 (72%) venous repairs were done and 33 (27.9%) were treated by ligation. Arteriovenous fistulas were found in 20 (16.9%) venous injuries. Venous injuries were associated with 10 (62.5%) amputations and 5 (45.4%) deaths. In the early postoperative period the authors found 15 (17.6%) thromboses of venous reconstructions.