Frequency of motor alterations detected through manometry in patients with esophageal symptoms and scleroderma. / Frecuencia de alteraciones motoras detectadas por manometría en pacientes con síntomas esofágicos y esclerodermia.

BACKGROUND: Scleroderma can present with esophageal involvement causing important morbidity. AIMS: To describe the manometric findings and clinical characteristics of patients with scleroderma and esophageal symptoms. MATERIALS AND METHODS: Patients with scleroderma and esophageal symptoms were evaluated through esophageal manometry within the time frame of one year. Descriptive statistics were carried out and the continuous variables were expressed as means and standard deviation. Frequencies were expressed as percentages. RESULTS: The study included 24 female patients with a mean age of 53.5 years and mean disease progression of 7.84 years. The most frequent findings were short and hypotonic lower esophageal sphincter (mean length 1.58cm and mean tone 9.49mmHg) and ineffective esophageal motility (mean non-transmitted waves 92.91%, mean effective primary peristalsis 40.05%, and mean amplitude 13.11mmHg). The most frequent symptom was dysphagia. CONCLUSIONS: Scleroderma is associated with lower esophageal sphincter alterations and symptomatic ineffective esophageal motility.

Clinical response in Mexican patients with irritable bowel syndrome treated with a low diet low in fermentable carbohydrates (FODMAP).

BACKGROUND: The low FODMAP diet eliminates carbohydrates and fermentable alcohols because they are not absorbed by the intestine, but are fermented by the microbiota, causing bloating and flatulence. AIMS: To evaluate the clinical response to the low FODMAP diet in patients with the different clinical subtypes of irritable bowel syndrome (IBS). MATERIALS AND METHODS: Patients attended to at the Gastroenterology Department in 2014 that were diagnosed with IBS based on the Rome III criteria were included in the study. They were managed with a low FODMAP diet for 21 days and their response to the symptoms of abdominal pain, bloating, flatulence, and stool form pre and post-diet were evaluated through the visual analogue scale, Bristol scale, and patient overall satisfaction. The results were analyzed by means, 95% CI, and the Student's t test. RESULTS: Of the 31 patients included in the study, 87% were women and the mean age was 46.48 years. Distribution was: IBS-C 64.5%, IBS-D 22.6%, and IBS-M 12.9%. The score for pain was 6.0 (95% CI 5.04-6.96) and the post-diet score was 2.77 (95% CI 1.60-3.95) (P<.001). The score for bloating was 7.10 (95% CI 6.13-8.06) and the post-diet score was 4.19 (95% CI 2.95-5.44) (P<.001). The score for flatulence was 5.94 (95% CI 4.79-7.08) and the post-diet score was 3.06 (IC95% 1.99-4.14) (P<.001). The pre-diet Bristol Scale result was 3.68 (95% CI 3.14-4.22) and the post-diet result was 4.10 (95% CI 3.66-4.54) (P=.1). The satisfaction percentage was 70.9%. CONCLUSIONS: In this first study on a Mexican population with IBS, there was significant improvement of the main symptoms, including pain, bloating, and flatulence after treatment with a low FODMAP diet.

Bases inmunológicas de la hipopigmentación vitiligoide asociada a melanoma / Immunological Basis of Melanoma-Associated Vitiligo-Like Depigmentation

El vitíligo es una patología cutánea que se manifiesta en forma de manchas hipocrómicas y acrómicas. Se caracteriza por la pérdida de melanocitos y se ha hipotetizado que un mecanismo autoinmune podría estar estrechamente relacionado con este fenómeno de despigmentación. El melanoma es una neoplasia maligna derivada de los melanocitos, que es letal si no se trata oportunamente. La leucodermia es un fenómeno de despigmentación cutánea, que ocasionalmente se puede asociar a melanoma. Tanto en los pacientes con vitíligo como con melanoma se ha observado una respuesta inmune contra antígenos de las células melanocíticas, ya sea para la destrucción de los melanocitos normales como de las células tumorales. A través de diversos estudios en humanos y modelos animales se ha observado que, tanto la inmunidad humoral como la celular tienen un papel inmunorregulador en la citotoxicidad contra el tumor o contra las células melanocíticas. El estudio de los factores asociados a los mecanismos de inmunopatogenicidad antitumoral, así como a la autoinmunidad es, en potencia, una vía alternativa para el diagnóstico y tratamiento de patologías como el vitíligo y el melanoma maligno

Vitiligo is a skin condition characterized by white, hypopigmented macules. Melanocyte loss is a feature of the disease, and it has been hypothesized that an autoimmune mechanism could be responsible for the depigmentation. Melanoma is a malignancy that develops in melanocytes; if not detected and treated early, it is often deadly. Leukoderma, a condition characterized by depigmentation of the skin, is sometimes associated with malignant melanoma. An immune response against melanocyte antigens leading to destruction of either melanoma cells or melanocytes has been observed in both vitiligo and melanoma. Studies in animal models and humans have shown that humoral and cell-mediated immune responses are involved in modulating cytotoxic activity against tumor cells and normal melanocytes. The study of factors associated with anti-tumor immunopathogenic mechanisms —autoimmunity for example—may provide us with tools for the diagnosis and treatment of diseases such as vitiligo and malignant melanoma

Immunological basis of melanoma-associated vitiligo-like depigmentation.

Vitiligo is a skin condition characterized by white, hypopigmented macules. Melanocyte loss is a feature of the disease, and it has been hypothesized that an autoimmune mechanism could be responsible for the depigmentation. Melanoma is a malignancy that develops in melanocytes; if not detected and treated early, it is often deadly. Leukoderma, a condition characterized by depigmentation of the skin, is sometimes associated with malignant melanoma. An immune response against melanocyte antigens leading to destruction of either melanoma cells or melanocytes has been observed in both vitiligo and melanoma. Studies in animal models and humans have shown that humoral and cell-mediated immune responses are involved in modulating cytotoxic activity against tumor cells and normal melanocytes. The study of factors associated with anti-tumor immunopathogenic mechanisms -autoimmunity for example- may provide us with tools for the diagnosis and treatment of diseases such as vitiligo and malignant melanoma.

Recombinant adenovirus delivery of calreticulin-ESAT-6 produces an antigen-specific immune response but no protection against a Mycobacterium tuberculosis challenge.

Bacillus Calmette-Guerin (BCG) has failed to efficaciously control the worldwide spread of the disease. New vaccine development targets virulence antigens of Mycobacterium tuberculosis that are deleted in Mycobacterium bovis BCG. Immunization with ESAT-6 and CFP10 provides protection against M. tuberculosis in a murine infection model. Further, previous studies have shown that calreticulin increases the cell-mediated immune responses to antigens. Therefore, to test whether calreticulin enhances the immune response against M. tuberculosis antigens, we fused ESAT-6 to calreticulin and constructed a recombinant replication-deficient adenovirus to express the resulting fusion protein (AdCRT-ESAT-6). The adjuvant effect of calreticulin was assayed by measuring cytokine responses specific to ESAT-6. Recombinant adenovirus expressing the fusion protein produced higher levels of interferon-γ and tumour necrosis factor-α in response to ESAT-6. This immune response was not improved by the addition of CFP-10 to the CRT-ESAT-6 fusion protein (AdCRT-ESAT-6-CFP10). Mice immunized with these recombinant adenoviruses did not decrease the mycobacterial burden after low-dose aerosol infection with M. tuberculosis. We conclude that calreticulin can be used as an adjuvant to enhance the immune response against mycobacterial antigens, but it is not enough to protect against tuberculosis.

Lesion and electrical stimulation of the ventral tegmental area modify persistent nociceptive behavior in the rat.

The ventral tegmental area (VTA) has been traditionally related with the control of motor responses. However, some studies show that this area is also involved in the processing of nociceptive information. It has been reported that this nucleus participates in the dissociative analgesia phenomenon. In the few works where electrical stimulation and lesion of the VTA have been performed, evaluated with persistent or chronic pain related behaviors, contradictory results have been obtained. Thus, a more detailed analysis of the role of the VTA in persistent pain is needed. Two series of experiments were performed: lesions of this nucleus were done with radiofrequency, (bilaterally at two points per side using a temperature range from 50 to 80 degrees C), and the VTA was electrically stimulated (10 min daily over 5 days, 2 ms rectangular pulses at 100 Hz during 1 s every 5 s) using two different schemes:10 min before the induction of the nociceptive stimulus and 90 min after the induction of the nociceptive stimulus. The latter allowed us to distinguish if the VTA electrical stimulation had a distinctive antinociceptive effect when applied before or after the induction of the nociceptive stimulus on a persistent pain related behavioral response in the rat, the self injury behavior (SIB). Our results showed that VTA lesions enhanced the occurrence of SIB; while activation of this same nucleus by electrical stimulation after the nociceptive stimulus, but not before, facilitates the analgesic process, expressed as a 1 day delay in SIB onset. These results indicate that the VTA is a brain structure that plays a key role in the processing and modulation of persistent pain information. Data are discussed in terms of the relationship of the VTA with the affective component of pain.

Immune response to Nocardia brasiliensis antigens in an experimental model of actinomycetoma in BALB/c mice.

Nine- to twelve-week-old BALB/c mice were injected in footpads with 10(7) CFU of a Nocardia brasiliensis cell suspension. Typical actinomycetoma lesions, characterized by severe local inflammation with abscess and fistula formation, were fully established by day 28 after infection. These changes presented for 90 days, and then tissue repair with scar formation slowly appeared, with complete healing after 150 days of infection. Some animals developed bone destruction in the affected area. Histopathology showed an intense inflammatory response, with polymorphonuclear cells and hyaloid material around the colonies of the bacteria, some of which were discharged from draining abscesses. Sera from experimental animals were analyzed by Western blotting, and immunodominant antigens P61 and P24 were found as major targets for antibody response. Anti-P24 immunoglobulin M (IgM) isotype antibodies were present as early as 7 days, IgG peaking 45 days after infection. Lymphocyte proliferation with spleen and popliteal lymph node cells demonstrated thymidine incorporation at 7 days after infection, the stimulation index decreasing by day 60. Levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, tumor necrosis factor alpha, and gamma interferon (IFN-gamma) were determined by enzyme-linked immunosorbent assay in the sera of infected animals. The circulating levels of IFN-gamma increased more than 10 times the basal levels; levels of IL-4, IL-6 and IL-10 also increased during the first 4 days of infection.

Electric stimulation of the cingulum bundle precipitates onset of autotomy induced by inflammation in rat.

The purpose of this work was to test if electric stimulation of the cingulum bundle in animals subjected to a hindpaw inflammatory process precipitates the onset and enhances autotomy behaviour. Wistar rats were implanted with bipolar parallel electrodes in the boundary of the cingulum bundle. The inflammatory process was induced in all subjects by injection of carrageenan. The groups were: A, sham; B, implanted and stimulated 10 min daily for 7 days; C, implanted and stimulated 2 h daily, for 7 days. Both groups were injected with CAR 2 days after ending the stimulation period; and D, implanted and stimulated 10 min daily for 5 days, the first stimulation being simultaneous to CAR injection. Results show that 100% of the subjects in stimulated groups presented autotomy as compared with 66% in the sham group. A significant shortening of the onset and increased rates in autotomy were observed in experimental groups (B, C and D) as compared to the sham group. We did not find differences between groups B and C, but there was an increment of autotomy in group D when compared with both B and C groups. We conclude that it is possible to facilitate the onset and to increase the intensity of the autotomy triggered by the inflammatory process with cingulum bundle electrical stimulation. The results also suggest that a fundamental condition to the development of the autotomy in this model is the presence of the noxious inflammatory process. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.