Effects of metoclopramide on mRNA levels of steroid 5á-reductase isozymes in prostate of adult rats

The rising incidence of prostate cancer and benign prostatic hypertrophy in the Western world is a cause of increasing public health concern. The most active androgen in the prostate is 5á-dihydrotestosterone obtained from testosterone (T) by the enzyme 5á-reductase (5á-R), expressed in the prostate as two isozymes, 5á-R1 and 5á-R2. These isozymes are involved in the growth and development of normal prostate and in the onset and progression of prostate disease. Besides androgens, prolactin (PRL) may also play a role, although it is not clear whether its effects on the prostate are in synergism with or independent of those of androgens. We previously demonstrated that sulpiride, an inductor of hyperprolactinemia, increased mRNA levels of 5á-R isozymes in prostate of adult rat. We hypothesized a possible interrelationship between PRL levels and 5á-R, although the effects of sulpiride per se cannot be ruled out. In the present study, one-step quantitative reverse transcription polymerase chain reaction coupled with laser-induced fluorescence capillary electrophoresis was used to quantify mRNA levels of both 5á-R isozymes in prostate of adult rat after administration of metoclopramide (MTC), another inductor of PRL secretion. With the administration regimens studied, MTC produced an increase in prostate weight and mRNA levels of 5á-R1 and 5á-R2 in adult rats. Given our finding that MTC per se or MTC-induced hyperprolactinemia modifies prostate disease-related parameters in animals with reduced plasma T levels, further investigation is warranted into the possibility that MTC use by aging males may increase their risk of prostate disease (AU)

Effects of metoclopramide on mRNA levels of steroid 5α-reductase isozymes in prostate of adult rats.

The rising incidence of prostate cancer and benign prostatic hypertrophy in the Western world is a cause of increasing public health concern. The most active androgen in the prostate is 5α-dihydrotestosterone obtained from testosterone (T) by the enzyme 5α-reductase (5α-R), expressed in the prostate as two isozymes, 5α-R1 and 5α-R2. These isozymes are involved in the growth and development of normal prostate and in the onset and progression of prostate disease. Besides androgens, prolactin (PRL) may also play a role, although it is not clear whether its effects on the prostate are in synergism with or independent of those of androgens. We previously demonstrated that sulpiride, an inductor of hyperprolactinemia, increased mRNA levels of 5α-R isozymes in prostate of adult rat. We hypothesized a possible interrelationship between PRL levels and 5α-R, although the effects of sulpiride per se cannot be ruled out. In the present study, one-step quantitative reverse transcription polymerase chain reaction coupled with laser-induced fluorescence capillary electrophoresis was used to quantify mRNA levels of both 5α-R isozymes in prostate of adult rat after administration of metoclopramide (MTC), another inductor of PRL secretion. With the administration regimens studied, MTC produced an increase in prostate weight and mRNA levels of 5α-R1 and 5α-R2 in adult rats. Given our finding that MTC per se or MTC-induced hyperprolactinemia modifies prostate disease-related parameters in animals with reduced plasma T levels, further investigation is warranted into the possibility that MTC use by aging males may increase their risk of prostate disease.

Natural killer receptors on CD8 T cells and natural killer cells from different HLA-C phenotypes in melanoma patients.

PURPOSE: Because immune mechanisms involved in cutaneous melanoma have not been fully elucidated, efforts have been made to achieve prognosis markers and potential targets for immune therapies, but they have not been entirely fruitful thus far. Therefore, the goal of this study was to investigate the involvement of early changes in CD8 T cells and CD56 natural killer (NK) cells expressing NK receptors in different HLA-C dimorphism groups of melanoma patients. EXPERIMENTAL DESIGN: CD8 T cells and CD56 NK cells were analyzed in 41 patients and 39 sex- and age-matched controls with different HLA-C genotypes by flow cytometry. HLA-C dimorphism at position 80 was tested by PCR sequence-specific primers and PCR sequence-specific oligonucleotide to examine whether it could mediate in the emergence of cells expressing killer cell immunoglobulin-like receptors. RESULTS: Thirty-five of 41 patients had benign sentinel node, and showed an imbalance in the absolute number of CD8(+)DR(+) or CD8(+)CD161(+) peripheral blood T cells according to the CD28 coexpression compared with controls. CD8(+)CD28(-)CD158a(+) T and CD56(+)CD158a(+) NK cells were significantly increased in HLA-C(Lys80) homozygous nonmetastatic patients, whereas only CD56(+)CD158a(+) NK cells increased in heterozygous ones. An up-regulation of the CD158a KIR receptor was also seen on NK cells but not in T cells of patients at advanced disease stages. CONCLUSIONS: This work provides, for the first time, evidence of immune activation in early stages of cutaneous melanoma, together with an increase of cells expressing CD158a in patients bearing the corresponding HLA-C ligand, which may be important to evaluate the disease progression and to use individualized immune therapeutic approaches.

HLA class I and class II frequencies in patients with cutaneous malignant melanoma from southeastern Spain: the role of HLA-C in disease prognosis.

Available data have led to a controversy on the relationship between human leukocyte antigen (HLA) and cutaneous malignant melanoma susceptibility or prognosis. Moreover, the influence of HLA-C on melanoma has not yet been well established. Therefore, the aim of the current study was to analyze the possible influence of the HLA system on melanoma susceptibility and prognosis in the Spanish population. For this purpose, HLA-A and HLA-B serotyping and HLA-C, HLA-DRB1, and HLA-DQB1 genotyping by polymerase chain reactions using sequence-specific oligonucleotide (PCR-SSO) and sequence-specific primer (PCR-SSP) were performed in 174 melanoma patients and 227 ethnically matched controls. The number of controls was increased up to 356 for HLA-C typing. Patients were stratified according to the histological subtypes of melanoma, sentinel lymph node status, tumor thickness, and ulceration of primary lesion. No HLA-A, HLA-B, HLA-DRB1, or HLA-DQB1 relationship with melanoma was observed for susceptibility or disease prognosis. However, the analysis of HLA-C locus showed that individuals homozygous for HLA-C(Lys80) were significantly more frequent within the patient than the control group. Remarkably, individuals homozygous for group 2 HLA-C alleles (HLA-C(Lys80)) seem to be associated with metastatic progression of melanoma. In contrast, we found a negative association between group 1 HLA-C alleles (HLA-C(Asn80)) and disease susceptibility or metastasis development. In conclusion, although an association with HLA-A, HLA-B, HLA-DRB1, or HLA-DQB1 was not demonstrated, the study of the HLA-C locus revealed that the analysis of the dimorphism at position 80 in the alpha1 helix may help to evaluate the risk and prognosis of melanoma in our population.

Penfigoide ampolloso en lactante tras vacunación / Bullous pemphigoid in an infant after vaccination

El penfigoide ampolloso es una enfermedad que característicamente afecta a personas de edad avanzada aunque se han descrito casos en niños. Presentamos un caso de penfigoide ampolloso en una lactante de 2 meses de vida con lesiones ampollosas en palmas y plantas, que aparecieron una semana después de recibir la primera dosis de la vacuna contra la hepatitis B, poliomielitis, difteria-tétanos-pertussis (DTP) y Haemophilus. Recibió tratamiento con agua sulfatada, dexametasona y ácido fusídico, con lo que desaparecieron las lesiones. Un mes después presentó un nuevo brote, más generalizado, a los 3 días de la segunda dosis de la misma vacuna. La erupción cutánea cedió por completo a los 3 meses de instaurar tratamiento con deflazacort (1 mg/kg/día). Tras 5 años de seguimiento, no ha vuelto a presentar lesiones a pesar de haber recibido el resto de vacunas del calendario oficial

Bullous pemphigoid (BP) is a disease that characteristically affects the elderly, although cases have been described in children. We present a case of BP in a twomonth- old infant with bullous lesions on the palms and soles, which appeared one week after receiving the first dose of the hepatitis B, polio, DTP and HiB vaccine. She was treated with sulphated water, dexamethasone and fusidic acid, and the lesions disappeared. One month later, she presented with a new, more generalized outbreak, three days after the second dose of the same vaccine. The skin eruption completely subsided 3 months after treatment with deflazacort was initiated (1 mg/kg/day). After five years of follow up, the patient has not presented with lesions again, despite having received the rest of the vaccines on the official schedule

Estudio prospectivo de los niveles de citocinas séricas en pacientes con melanoma: valor pronóstico / Prospective study of the levels of serum cytokines in patients with melanoma: prognostic value

Introducción. La producción de citocinas tiene un papel primordial en la lucha antitumoral por parte del sistema inmunitario. Por ello, en este trabajo nos propusimos investigar si las concentraciones séricas de distintos tipos de citocinas en pacientes con melanoma se asociaban con la evolución de su enfermedad. Material y métodos. Se analiza la variación en los niveles séricos de citocinas representativas de los fenotipos Th1 (interferón gamma [IFN-gama] e interleucina 15 [IL-15]) y Th2 (IL-6 e IL-10) en 33 pacientes con melanoma cutáneo primario. Se obtuvieron semestralmente muestras de sangre periférica hasta conseguir un total de cuatro muestras por paciente. Resultados. A los 30 meses, 29 pacientes (87,9 %) sobrevivieron sin signos de recidiva. La IL-10 basal era más alta en el grupo de enfermos que fallecieron que en los supervivientes. En los pacientes que fallecieron se observó un aumento de la IL-6 sérica en la última muestra. No se pudo demostrar ninguna relación entre los niveles de IFN-gama e IL-15 y la progresión del melanoma. Conclusión. La determinación de citocinas de tipo Th2 (IL-6 e IL-10) en suero de pacientes con melanoma podría ser útil en el seguimiento clínico de estos enfermos y servir como factor predictivo de la mejor o peor evolución de la enfermedad, en el sentido de un peor pronóstico para los enfermos con niveles elevados de IL-10 e IL-6. Por el contrario, la determinación de los niveles séricos de las citocinas de tipo Th1 (IL-15 e IFN-gama) no parece de tanta utilidad a la hora de orientar sobre el pronóstico

Introduction. The production of cytokines plays a primordial role in the immune system’s fight against tumors. Therefore, we proposed to investigate whether the serum levels of different types of cytokines in melanoma patients were associated with the evolution of their disease. Material and methods. We analyzed the variation in the serum levels of cytokines representative of the Th1 (INF-gamma and IL-15) and Th2 (IL-6 and IL-10) phenotypes in 33 patients with primary cutaneous melanoma. Peripheral blood samples were obtained every six months until we had a total of 4 samples per patient. Results. After 30 months, 29 patients (87.9 %) had survived with no signs of recurrence. Basal IL-10 serum levels were higher in the group of patients who expired than in the survivors. Among the patients who expired, an increase in IL-6 serum levels was observed in the last sample. No relationship could be proven between INF-gamma and IL-15 levels and melanoma progression. Conclusion. Determining the levels of type Th2 cytokines (IL-6 and IL-10) in the serum of melanoma patients could be useful in the clinical follow-up of these patients and serve as a predictive factor for the progression of the disease, with the prognosis being worse for patients with high IL-10 and IL-6 levels. On the other hand, determining the serum levels of type Th1 cytokines (IL-15 and INF-gamma) does not seem to be as useful in predicting the prognosis

[Prospective study of the levels of serum cytokines in patients with melanoma: prognostic value]. / Estudio prospectivo de los niveles de citocinas séricas en pacientes con melanoma: valor pronóstico.

INTRODUCTION: The production of cytokines plays a primordial role in the immune systems fight against tumors. Therefore, we proposed to investigate whether the serum levels of different types of cytokines in melanoma patients were associated with the evolution of their disease. MATERIAL AND METHODS: We analyzed the variation in the serum levels of cytokines representative of the Th1 (INFg and IL-15) and Th2 (IL-6 and IL-10) phenotypes in 33 patients with primary cutaneous melanoma. Peripheral blood samples were obtained every six months until we had a total of 4 samples per patient. RESULTS: After 30 months, 29 patients (87.9 %) had survived with no signs of recurrence. Basal IL-10 serum levels were higher in the group of patients who expired than in the survivors. Among the patients who expired, an increase in IL-6 serum levels was observed in the last sample. No relationship could be proven between INFg and IL-15 levels and melanoma progression. CONCLUSION: Determining the levels of type Th2 cytokines (IL-6 and IL-10) in the serum of melanoma patients could be useful in the clinical follow-up of these patients and serve as a predictive factor for the progression of the disease, with the prognosis being worse for patients with high IL-10 and IL-6 levels. On the other hand, determining the serum levels of type Th1 cytokines (IL-15 and INFg) does not seem to be as useful in predicting the prognosis.

[Bullous pemphigoid in an infant after vaccination]. / Penfigoide ampolloso en lactante tras vacunación.

Bullous pemphigoid (BP) is a disease that characteristically affects the elderly, although cases have been described in children. We present a case of BP in a two-month-old infant with bullous lesions on the palms and soles, which appeared one week after receiving the first dose of the hepatitis B, polio, DTP and HiB vaccine. She was treated with sulphated water, dexamethasone and fusidic acid, and the lesions disappeared. One month later, she presented with a new, more generalized outbreak, three days after the second dose of the same vaccine. The skin eruption completely subsided 3 months after treatment with deflazacort was initiated (1 mg/kg/day). After five years of follow up, the patient has not presented with lesions again, despite having received the rest of the vaccines on the official schedule.

Changes in the number of CD80(+), CD86(+), and CD28(+) peripheral blood lymphocytes have prognostic value in melanoma patients.

Our aim was to evaluate whether the number of circulating lymphocytes expressing costimulatory molecules can be associated with melanoma prognosis. We determined the concentration of peripheral blood lymphocytes, which expressed the CD80/CD86 or CD28/CTLA-4 molecules, in 38 patients with cutaneous melanoma and 27 controls. The number of each cell subset was compared between patients and controls, as well as between groups of patients stratified according to Breslow thickness of the primary tumor (< or = 2 mm vs > 2 mm) or to survival after 3 years. The concentration of circulating lymphocytes expressing the CD80/CD86 molecules was not significantly different between patients and controls. There was a lower number of CD3(+)CD8(+)CD28(+) cells, as well as a higher CD3(+)CD8(+)/CD3(+)CD8(+)CD28(+) cell ratio, in melanoma patients than in controls. Melanoma patients with thinner tumors and those surviving revealed an increase of CD19(+)CD80(+) and CD19(+)CD80(+)CD86(+) cells, as well as a higher concentration of CD3(+)CD4(+)CD28(+) cells. CD80(+) B cells and a low CD8 suppressor/cytolytic cell ratio correlate with a good prognosis in melanoma. Our findings support our conclusion that CD80(+) B cells may be important antigen presenting cells that can contribute to an antimelanoma immune response and are candidates to be monitored in melanoma patients.