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2.
Pol J Vet Sci ; 22(3): 573-579, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31560466

ABSTRACT

The development of in vitro embryo production (IVEP) techniques in Felis catus is a fitting model with potential application to the conservation of endangered felid species. To improve the quality of IVEP techniques an appropriate balance of pro- and antioxidants should be provided. Under in vitro conditions, high levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) mRNA provide a defence mechanism against oxidative stress for embryos. In order to improve the development of cat oocytes, the effects of SOD and CAT supplemented to in vitro maturation (IVM) medium and of GPx supplemented to in vitro fertilization (IVF) medium on development and embryo production in vitro were evaluated. Data showed an increase of 70 and 77 % of cleaved embryo and blastocyst formation, respectively, in the experiment with SOD and CAT addition to IVM medium; in the experiment with GPx addition to IVF medium the number of cleaved embryos doubled and the number of embryos increased by 96 %. Therefore, our results were positive and encourage us to continue studies on cat oocytes evaluating the effects of various dosages and combination of antioxidants.


Subject(s)
Antioxidants/pharmacology , Catalase/pharmacology , Cats/embryology , Embryo Culture Techniques/veterinary , Superoxide Dismutase/pharmacology , Animals , Antioxidants/administration & dosage , Catalase/chemistry , Catalase/metabolism , Culture Media/chemistry , Female , Fertilization in Vitro/veterinary , Glutathione Peroxidase/metabolism , Male , Superoxide Dismutase/chemistry , Superoxide Dismutase/metabolism
3.
Andrology ; 6(2): 351-361, 2018 03.
Article in English | MEDLINE | ID: mdl-29359412

ABSTRACT

Stallion semen is damaged by oxidative stress during cooling and transport. Semen processing and extenders have been tested to improve the fertilizing capacity of semen and to preserve semen during transport. Dietary supplementation with natural antioxidants has been proposed to prevent oxidative damages. In this study, for the first time, the effect of dietary supplementation with Lepidium meyenii (Maca) on the characteristics of fresh and chilled stallion semen was evaluated. Maca is a traditional Andean crop used as a nutraceutical for the fertility-enhancing properties that are linked with antioxidant activity. The diet of five stallions was supplemented with 20 g of Maca powder daily for a total of 60 days. A control group of five stallions received the same diet without Maca. Semen was collected once before the administration of Maca (D0), twice during the administration at 30 and 60 days (D30 and D60), and finally twice at 30 and 60 days after the end of the administration (D90 and D120). Ejaculates were processed for cooled shipping at 5 °C and evaluated in the laboratory for total and progressive motility, acrosome integrity, and lipid peroxidation after collection and after 24, 48, and 72 h of storage. Dietary supplementation with Maca improved sperm concentration (from 213 ± 80.4 to 447 ± 73.1 × 106 spz/mL) and total sperm count (from 10,880 ± 4377 to 24,783 ± 4419 × 106 spz). The beneficial effects of Maca supplementation on motility and acrosome integrity in the raw semen were detected from the end of treatment with Maca (D60) until the end of the study (D120). Furthermore, during cooling storage, total motility, progressive motility, and acrosome integrity declined more slowly in the Maca-treated group than in the control group. Lipid peroxidation did not change during cooling storage in either group and did not show a significant difference between the two groups. In this study, the dietary supplementation with Maca increased sperm production and stabilized semen quality during chilled storage.


Subject(s)
Antioxidants/pharmacology , Dietary Supplements , Horses , Lepidium , Semen Preservation , Spermatogenesis/drug effects , Spermatozoa/drug effects , Animals , Cryopreservation , Lipid Peroxidation , Male
4.
Actas urol. esp ; 39(1): 57-62, ene.-feb. 2015.
Article in Spanish | IBECS | ID: ibc-132178

ABSTRACT

Introducción: La orquiectomía radical (OR) se considera todavía la opción estándar de atención para los tumores malignos de células germinales, que representan la gran mayoría de las masas testiculares palpables. En pacientes diagnosticados con pequeñas masas testiculares la cirugía conservadora testicular (CCT) podría ser un tratamiento alternativo a la OR. El objetivo de esta revisión actualizada es evaluar las indicaciones actuales para la CCT y debatir los resultados oncológicos y funcionales de los pacientes sometidos a cirugía conservadora testicular por pequeñas masas testiculares. Adquisición de la evidencia: Se ha llevado a cabo una revisión no sistemática de la literatura empleando la base de datos Medline, que incluyó un protocolo de texto libre utilizando los términos «cirugía conservadora de los testículos», «cirugía conservadora testicular», «orquiectomía parcial», «tumor de testículo», «tumor del cordón sexual» y «función testicular». También se evaluaron otros estudios significativos citados en las listas de referencia de los trabajos seleccionados. Síntesis de la evidencia: Aún no se ha registrado ningún ensayo controlado aleatorizado comparando la CCT con la OR. En aquellos pacientes con testículos contralaterales normales el uso de la CCT todavía resulta controvertido. En casos seleccionados de masas gonadales < 2 cm la CCT parece ser una opción terapéutica segura y viable. El análisis de secciones congeladas permite distinguir entre neoplasias benignas y malignas durante la CCT. Los resultados del seguimiento a medio y largo plazo no mostraron ningún riesgo significativo de recidiva local y a distancia en las principales series de la literatura. Conclusiones: La CCT es un tratamiento efectivo para las pequeñas masas testiculares en pacientes seleccionados, limitando los sobretratamientos quirúrgicos innecesarios, sin comprometer los resultados oncológicos y funcionales. Se requieren más estudios para confirmar la seguridad oncológica


Introduction: Radical orchiectomy (RO) is still considered the standard of care for malignant germ cell tumors, which represent the vast majority of the palpable testicular masses. In those patients diagnosed with small testicular masses (STMs), testis-sparing surgery (TSS) could be an alternative treatment to RO. The aim of this updated review is to evaluate the current indications for TSS, and discuss the oncological and functional results of patients who had undergone organ-sparing surgery for STMs. Evidence acquisition: A non-systematic review of the Literature using the Medline database has been performed, including a free-text protocol using the terms «testis sparing surgery», «testicular sparing surgery», «partial orchiectomy», «testis tumor», «sex cord tumor», and «testis function». Other significant studies cited in the reference lists of the selected papers were also evaluated. Evidence synthesis: No randomized controlled trials comparing TSS with radical orchiectomy have been reported yet. In those patients with normal contra-lateral testis, the use of TSS is still controversial. In selected cases of gonadal masses < 2 cm, TSS seems to be a safe and feasible treatment option. Frozen section examination allows us to discriminate between benign and malignant neoplasms during TSS. Intermediate and long-term follow-up results showed no significant risk of local and distant recurrences in the main series reported in the literature. Conclusions: TSS is an effective treatment for STMs in selected patients, limiting the unnecessary surgical over-treatments, without compromising the oncological and functional outcomes. Further studies are needed in order to confirm the oncological safety


Subject(s)
Humans , Male , Testicular Neoplasms/surgery , Orchiectomy/methods , Organ Sparing Treatments/methods , Treatment Outcome , Recovery of Function
5.
Actas Urol Esp ; 39(1): 57-62, 2015.
Article in English, Spanish | MEDLINE | ID: mdl-24775811

ABSTRACT

INTRODUCTION: Radical orchiectomy (RO) is still considered the standard of care for malignant germ cell tumours, which represent the vast majority of the palpable testicular masses. In those patients diagnosed with small testicular masses (STMs), testis-sparing surgery (TSS) could be an alternative treatment to RO. The aim of this updated review is to evaluate the current indications for TSS, and discuss the oncological and functional results of patients who had undergone organ-sparing surgery for STMs. EVIDENCE ACQUISITION: A non-systematic review of the Literature using the Medline database has been performed, including a free-text protocol using the terms "testis-sparing surgery", "testicular sparing surgery", "partial orchiectomy", "testis tumour", "sex cord tumour", and "testis function". Other significant studies cited in the reference lists of the selected papers were also evaluated. EVIDENCE SYNTHESIS: No randomized controlled trials comparing TSS with radical orchiectomy have been reported yet. In those patients with normal contra-lateral testis, the use of TSS is still controversial. In selected cases of gonadal masses < 2 cm, TSS seems to be a safe and feasible treatment option. Frozen section examination allows us to discriminate between benign and malignant neoplasms during TSS. Intermediate and long-term follow-up results showed no significant risk of local and distant recurrences in the main series reported in the literature. CONCLUSIONS: TSS is an effective treatment for STMs in selected patients, limiting the unnecessary surgical over-treatments, without compromising the oncological and functional outcomes. Further studies are needed in order to confirm the oncological safety.


Subject(s)
Conservative Treatment , Organ Sparing Treatments/methods , Testicular Neoplasms/surgery , Humans , Male , Orchiectomy , Recovery of Function , Testicular Neoplasms/pathology , Testis , Treatment Outcome
6.
Ann N Y Acad Sci ; 966: 91-6, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12114263

ABSTRACT

This paper aims to evaluate adrenal gland hormone levels in patients with polymyalgia rheumatica (PMR) during glucocorticoid (GC) therapy. A lower than expected basal production of cortisol was found in active and glucocorticoid-untreated PMR patients, particularly females. The abrupt onset of PMR with clinical features similar to those of the steroid-withdrawal syndrome or adrenal insufficiency, as well as the clinical response to GC therapy in elderly people already age-disposed to an inadequate adrenal and anti-inflammatory response, might represent the most significant pathophysiological basis of the disease.


Subject(s)
Adrenal Cortex/metabolism , Androstenedione/blood , Dehydroepiandrosterone/blood , Hydrocortisone/blood , Polymyalgia Rheumatica/drug therapy , Testis/metabolism , Adrenal Cortex/drug effects , Adrenal Hyperplasia, Congenital , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/metabolism , Aged , Aging/immunology , Aging/physiology , Androstenedione/metabolism , Area Under Curve , Biomarkers , Blood Sedimentation , C-Reactive Protein/analysis , Corticotropin-Releasing Hormone , Dehydroepiandrosterone/metabolism , Female , Humans , Hydrocortisone/deficiency , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Inflammation , Interleukin-6/blood , Male , Neuroimmunomodulation , Pituitary-Adrenal System/physiopathology , Polymyalgia Rheumatica/blood , Polymyalgia Rheumatica/immunology , Polymyalgia Rheumatica/physiopathology , Secretory Rate/drug effects , Testis/drug effects
7.
Reumatismo ; 53(3): 204-209, 2001.
Article in Italian | MEDLINE | ID: mdl-12167972

ABSTRACT

Various factors such as immunogenetic determinants, sex, age and stress play an important role in the pathogenesis of rheumatoid arthritis (RA). The relationship between stress and RA is still unclear and undefined; however, various lines of research are developing in order to evaluate environmental, psychologic, and biologic stressors as predisposing factors. The aim of our study was to evaluate whether stress-related psychologic factors and personality disorders might be involved in the development of RA, by using a psychometric investigation-methodology in a series of patients. Twenty-three patients underwent a clinical interview and other specific psychometric tests. Macro and microstressful life-events preceded RA in 83% of the cases. Sixty percent of the patients showed a correlation between flare-ups of the disease and appearance of microevents. An obsessive-compulsive personality was found in 26% of the patients. Anxia was detected in 40% of the patients. Among the group of patients with borderline disorder's was also detected alexithymia. The high prevalence of major life-events preceding the onset of RA and the presence of personality disorders support the role of the altered stress response system as an important pathogenetic factor in the disease.

8.
Z Rheumatol ; 59 Suppl 2: II/65-9, 2000.
Article in English | MEDLINE | ID: mdl-11155807

ABSTRACT

The altered cortisol and adrenal androgen (i.e., dehydroepiandrosterone sulfate = DHEAS) secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with corticosteroids, should be clearly regarded as a "relative adrenal insufficiency" in the setting of a sustained inflammatory process, as shown by high serum IL-6 levels. Androgens seem implicated in the pathophysiology of autoimmune disorders, including RA, as natural immunosuppressors. Low plasma and synovial fluid testosterone concentrations are observed in male RA patients; low plasma DHEAS levels are mainly observed in female RA patients. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). Gene polymorphisms for enzymes involved in the steroidogenesis seem to further complicate the role of sex hormones in the susceptibility to autoimmunity. Acquired changes of sex steroid metabolism seem to also play a role in the peripheral sex hormone levels. In conclusion, a complex interaction between the hypothalamus-pituitary-adrenocortical and gonadal axis functions is evident in RA.


Subject(s)
Arthritis, Rheumatoid/immunology , Dehydroepiandrosterone Sulfate/blood , Hypothalamo-Hypophyseal System/physiopathology , Pituitary-Adrenal System/physiopathology , Testosterone/blood , Adrenal Insufficiency/immunology , Autoimmune Diseases/immunology , Female , Humans , Hydrocortisone/blood , Interleukin-6/blood , Male
9.
Ann N Y Acad Sci ; 917: 835-43, 2000.
Article in English | MEDLINE | ID: mdl-11268413

ABSTRACT

The hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes involvement or response to immune activation seems crucial for the control of excessive inflammatory and immune conditions such as autoimmune rheumatic diseases, including rheumatoid arthritis (RA). However, female patients seem to depend more on the HPA axis, whereas male patients seem to depend more on the HPG axis. In particular, hypoandrogenism may play a pathogenetic role in male RA patients because adrenal and gonadal androgens, both products of the HPA and HPG axes, are considered natural immunosuppressors. A significantly altered steroidogenesis of adrenal androgens (i.e., dehydroepiandrosterone sulfate, DHEAS and DHEA) in nonglucocorticoid-treated premenopausal RA patients has been described. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). A range of physical and psychosocial stressors are also implicated in the activation of the HPA axis and related HPG changes. Chronic and acute stressors appear to have different actions on immune mechanisms with experimental and human studies indicating that acute severe stressors may be even immunosuppressive, while chronic stress may enhance immune responses. The interactions between the immunological and neuroendocrine circuits is the subject of active and extensive ongoing research and might in the near future offer highly promising strategies for hormone-replacement therapies in RA.


Subject(s)
Arthritis, Rheumatoid/physiopathology , Hypothalamo-Hypophyseal System/physiopathology , Neuroimmunomodulation , Pituitary-Adrenal System/physiopathology , Animals , Arthritis, Rheumatoid/immunology , Humans , Hypothalamo-Hypophyseal System/immunology , Pituitary-Adrenal System/immunology
11.
Prensa méd. argent ; 86(7): 698-705, sept. 1999. graf
Article in Spanish | LILACS | ID: lil-243183

ABSTRACT

Se estudiaron 1625 pacientes portadores de dolor cólico abdominal agudo (cólico intestinal y renal, discinesia biliar con o sin litiasis, dispepsia no ulcerosa, dismenorrea, movilización del DIU y criocirugía del cuello uterino) que presentaron al momento de la incorporación dolor de intensidad moderada o severa. Fueron asignados al azar y doble ciego en 2 grupos expermientales con Clonixinato de lisina 125 mg asociado a Propinox 10 mg (CLP) (N=818) o N-butilbromuro de hioscina 10 mg asociado a Paracetamol 500 mg (PB) (N=807). El tratamiento consistió en un comprimido, de igual aspecto en ambas drogas, como dosis única. El efecto analgésico-antiespasmódico fue evaluado horariamente durante un lapso de 4 hs. En cada control se estabaleció la evolución del dolor, como así también de otros síntomas acompañantes, mediante escala visual análoga (EVA) de 10 cm y escala de categorización verbal de 4 niveles. Asimismo, en cada oportunidad se indagaron la frecuencia de eventos adversos. En el control final de las 4 horas el paciente y el médico efectuaron una evaluación global sobre la eficacia y tolerancia al tratamiento. Ambos grupos fueron equivalentes entre sí en lo referente a condiciones basales (características demográficas, etiológicas y dolor espontáneo), por lo que se asume que se trata de muestras homogéneas y comparables entre sí. Con ambos métodos de registro se demostró una reducción progresiva de la intensidad del dolor, que se hizo significativa a partir del control de la 1a. hora, con una reducción para los 2 tratamientos en alrededor de un 43 por ciento respecto del valor inicial.La actividad analgésica sostenida queda demostrada para ambos tratamientos en razón que en el control final de las 4 hs los valores de EVA fueron menores de 1. La salida del ensayo por ineficacia en el control de la 1a. hora fue similar: 14 por ciento por el CLLP y 12 por ciento para PB. No se demostraron diferencias estadísticas en las intensidades de dolor en cada tiempo entre los 2 tratamientos. Los signos y síntomas asociados a la patología de inclusión (cefaleas, náuseas y diarrea) se redujeron significativamente entre la 1a. y 2da. hora de control. Se observó un ligero incremento (no significtivo) en la incidencia de boca seca y visión borrosa. La evaluación global de eficacia analgésica fue considerada buena en el 81 por ciento (CLP) y 80 por ciento (PB) de las opiniones de médico y en un 78 por ciento y 79 por ciento respectivamente cuando lo hizo el paciente


Subject(s)
Humans , Adult , Abdomen, Acute/therapy , Analgesics/administration & dosage , Pain , Pain/therapy , Parasympatholytics/administration & dosage
12.
Prensa méd. argent ; 86(7): 698-705, sept. 1999. graf
Article in Spanish | BINACIS | ID: bin-15020

ABSTRACT

Se estudiaron 1625 pacientes portadores de dolor cólico abdominal agudo (cólico intestinal y renal, discinesia biliar con o sin litiasis, dispepsia no ulcerosa, dismenorrea, movilización del DIU y criocirugía del cuello uterino) que presentaron al momento de la incorporación dolor de intensidad moderada o severa. Fueron asignados al azar y doble ciego en 2 grupos expermientales con Clonixinato de lisina 125 mg asociado a Propinox 10 mg (CLP) (N=818) o N-butilbromuro de hioscina 10 mg asociado a Paracetamol 500 mg (PB) (N=807). El tratamiento consistió en un comprimido, de igual aspecto en ambas drogas, como dosis única. El efecto analgésico-antiespasmódico fue evaluado horariamente durante un lapso de 4 hs. En cada control se estabaleció la evolución del dolor, como así también de otros síntomas acompañantes, mediante escala visual análoga (EVA) de 10 cm y escala de categorización verbal de 4 niveles. Asimismo, en cada oportunidad se indagaron la frecuencia de eventos adversos. En el control final de las 4 horas el paciente y el médico efectuaron una evaluación global sobre la eficacia y tolerancia al tratamiento. Ambos grupos fueron equivalentes entre sí en lo referente a condiciones basales (características demográficas, etiológicas y dolor espontáneo), por lo que se asume que se trata de muestras homogéneas y comparables entre sí. Con ambos métodos de registro se demostró una reducción progresiva de la intensidad del dolor, que se hizo significativa a partir del control de la 1a. hora, con una reducción para los 2 tratamientos en alrededor de un 43 por ciento respecto del valor inicial.La actividad analgésica sostenida queda demostrada para ambos tratamientos en razón que en el control final de las 4 hs los valores de EVA fueron menores de 1. La salida del ensayo por ineficacia en el control de la 1a. hora fue similar: 14 por ciento por el CLLP y 12 por ciento para PB. No se demostraron diferencias estadísticas en las intensidades de dolor en cada tiempo entre los 2 tratamientos. Los signos y síntomas asociados a la patología de inclusión (cefaleas, náuseas y diarrea) se redujeron significativamente entre la 1a. y 2da. hora de control. Se observó un ligero incremento (no significtivo) en la incidencia de boca seca y visión borrosa. La evaluación global de eficacia analgésica fue considerada buena en el 81 por ciento (CLP) y 80 por ciento (PB) de las opiniones de médico y en un 78 por ciento y 79 por ciento respectivamente cuando lo hizo el paciente


Subject(s)
Humans , Adult , Abdomen, Acute/therapy , Pain/diagnostic imaging , Pain/therapy , Parasympatholytics/administration & dosage , Analgesics/administration & dosage
13.
Int J Tissue React ; 21(1): 13-8, 1999.
Article in English | MEDLINE | ID: mdl-10463136

ABSTRACT

The aim of this study was to assess the efficacy and tolerance of propinox administered i.v., and establish a dose-response relation according to three dose levels (10, 20 and 30 mg), vs. placebo in patients with moderate to severe acute biliary pain. Three hundred and fifty patients were included: 85 received placebo treatment, 81 were treated with propinox 10 mg, 91 with propinox 20 mg and 93 received propinox 30 mg. Spontaneous pain intensity was assessed according to a visual analog and a verbal scale before treatment and 20, 60 and 120 min after. All treatments induced significant and progressive pain reduction at all controls, but patients treated with 20 and 30 mg of propinox showed significantly lower pain intensity after 120 min compared to the placebo group. The last control revealed that 28% of patients receiving placebo had no pain while 60% of patients treated with propinox 30 mg reported absence of pain with a statistically significant difference (p < 0.001). All treatments were very well tolerated and there were no dropouts due to adverse events. Mouth dryness was the adverse effect occurring with a significantly higher frequency than that observed with placebo although it was only seen in patients treated with 20 mg and 30 mg active doses. The results of this study showed that propinox was an effective drug in the treatment of moderate to severe colic pain of biliary origin. Concerning efficacy and side effects, a clear dose-response relation was observed; the 20 mg and 30 mg doses being significantly superior to placebo.


Subject(s)
Colic/drug therapy , Gallstones/drug therapy , Mandelic Acids/therapeutic use , Acute Disease , Adult , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Pain , Prospective Studies
15.
Ann N Y Acad Sci ; 876: 419-25, 1999 Jun 22.
Article in English | MEDLINE | ID: mdl-10415637

ABSTRACT

Rheumatoid arthritis (RA) is an inflammatory chronic disease with an autoimmune pathogenesis and a complex multifactorial etiology. Various factors such as immunogenetic determinants, sex, age, and stress play an important role. The relationship between stress and RA is still unclear and undefined; however, various lines of research are developing in order to evaluate environmental, psychologic, and biologic stressors as predisposing factors. The aim of our study was to evaluate whether stress-related psychologic factors and personality disorders might be involved in the development of RA, by using a psychometric investigation-methodology in a series of patients. Fifteen in- and outpatients underwent a clinical interview and other specific psychometric tests. Macro- and microstressful life-events preceded RA onset in 86% of the cases. Sixty percent of the patients showed a correlation between flare-ups of the disease and appearance of microevents. Forty percent of the patients showed an obsessive-compulsive personality disorder (OCPD), 40% showed a borderline personality disorder (BPD), 7% showed a schizoid and a dependent disorder. Only 13% of the patients showed no personality disorders. Among the BPD group we also detected alexithymia. Our results should be considered as preliminary; on the other hand, the high prevalence of major life-events preceding the onset of RA and the presence of personality disorders support the role of the altered stress response system as an important pathogenetic factor and will be a matter of further studies.


Subject(s)
Adaptation, Psychological/physiology , Arthritis, Rheumatoid/psychology , Personality/physiology , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Adult , Aged , Arthritis, Rheumatoid/complications , Attitude , Borderline Personality Disorder/complications , Borderline Personality Disorder/psychology , Compulsive Personality Disorder/complications , Compulsive Personality Disorder/psychology , Female , Humans , Male , Middle Aged , Stress, Psychological/complications
16.
J Rheumatol ; 26(2): 282-8, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9972959

ABSTRACT

OBJECTIVE: To assess hypothalamic-pituitary-adrenocortical axis function in patients with rheumatoid arthritis (RA) not previously treated with glucocorticoids in relation to their inflammatory condition and in comparison to healthy controls. METHODS: We evaluated, in 10 premenopausal patients with RA and 7 age matched controls, plasma dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and cortisol concentrations, together with inflammatory cytokine levels [interleukin 6 (IL-6) and IL-12], both in basal conditions and after stimulation with ovine corticotropin releasing hormone (oCRH) and with low dose intravenous (5 microg) adrenocorticotropic hormone (ACTH). RESULTS: DHEA and DHEAS basal concentrations were found to be significantly lower (p<0.05) in premenopausal patients with RA than in controls. As expected, significantly higher basal levels of IL-6 and IL-12 (p<0.05) were found in patients with RA. After the low dose ACTH testing, the DHEA area under the curve value was found to be significantly lower (p<0.01) in patients than controls. Similar results, but without statistical significance, were observed after oCRH stimulation. DHEA levels at basal time showed a significant negative correlation with the erythrocyte sedimentation rate and platelet count, as well as with the Steinbrocker class of the disease (p<0.05). Normal plasma cortisol levels during oCRH and ACTH testing were found in patients with RA in spite of their inflammatory condition. After ACTH testing, IL-6 levels decreased significantly (p<0.05), whereas IL-12 levels were unchanged. No significant changes in IL-6 and IL-12 levels were found after oCRH testing. CONCLUSION: The abnormal androgen concentrations observed during testing in patients with RA might support the implication of adrenal androgens in the immune/inflammatory cytokine mediated mechanisms involved in the pathophysiology and clinical aspects of RA.


Subject(s)
Arthritis, Rheumatoid/blood , Glucocorticoids/therapeutic use , Hypothalamo-Hypophyseal System/metabolism , Pituitary-Adrenal System/metabolism , Premenopause/metabolism , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/pharmacology , Adult , Arthritis, Rheumatoid/drug therapy , Corticotropin-Releasing Hormone/pharmacology , Dehydroepiandrosterone/blood , Dehydroepiandrosterone Sulfate/blood , Dexamethasone/pharmacology , Estradiol/blood , Female , Humans , Hydrocortisone/blood , Interleukin-12/blood , Interleukin-6/blood , Radioimmunoassay , Testosterone/blood , Time Factors
17.
Eur J Endocrinol ; 138(3): 294-301, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9539304

ABSTRACT

OBJECTIVE: To ascertain whether a different regulation and sensitivity of the hypothalamic-pituitary-adrenal axis exists and whether a type of cortisol resistance is present in rheumatoid arthritis (RA) patients, a chronic disease in whose pathogenesis modifications of the steroid milieu are involved. DESIGN: We studied the basal and dynamic response of ACTH and adrenal steroids to various stimuli acting on the hypophysis or directly on the adrenal gland. METHODS: We studied ten RA patients (39.8 +/- 7.4 (S.D.) years), defined according to the American Rheumatism Association, and seven healthy control patients (34.1 +/- 9.6 (S.D.) years). All subjects underwent testing, in random order, with placebo, desmopressin (DDAVP) (10 microg i.v.), ovine corticotropin-releasing hormone (oCRH) (1 microg/kg body weight) and low-dose ACTH (5 microg i.v.), during the follicular phase of two different menstrual cycles. Blood samples were collected at different times for ACTH and adrenal steroids assay. Baseline estradiol (E2), testosterone and IGF-I levels were also evaluated. All subjects collected urine specimens for 24 h urine free cortisol (UFC). RESULTS: No difference in E2, testosterone or UFC was found between RA patients and controls. IGF-I levels were significantly (P < 0.01) lower in RA patients (110.6 +/- 6.4 microg/l) than in controls (207.0 +/- 37.9 microg/l). Mean baseline dehydroepiandrosterone (DHEA) and delta4-androstenedione levels of the four tests were significantly (P < 0.05) lower in RA patients than in controls. In RA, a negative correlation was found between mean DHEA levels, class of disease (r = -0.67, P < 0.05) and erythrocyte sedimentation rate (r = -0.63, P < 0.05). After placebo no difference in ACTH and cortisol area under curves (AUCs) was found between RA patients and controls. After DDAVP no cortisol or ACTH response was found in RA patients, while a significant (P < 0.05) ACTH release was found in controls. Only in RA patients was DDAVP able to induce a significant (P < 0.01) DHEA increase. After oCRH a similar significant response in ACTH (P < 0.05), cortisol (P < 0.01), and DHEA (P < 0.01) was found in both groups. After low-dose ACTH, a similar significant (P < 0.01) cortisol response was found in both RA patients and controls; indeed in RA patients DHEA AUC (2196.0 +/- 321.8 nmol/l per 90 min) was significantly lower (P < 0.01) than DHEA AUC (4280.8 +/- 749.0 nmol/l per 90 min) in controls. A similar significant (P < 0.01), though not abnormal, 17-hydroxyprogesterone response to ACTH was found in both groups. CONCLUSIONS: Our study underlines reduced adrenal steroid and IGF-I levels, but not the previously described cortisol resistance in RA patients; it shows that baseline and dynamic cortisol levels are 'normal' but inadequate in the setting of a sustained inflammatory disease like RA. The reduced basal and low-dose ACTH-induced DHEA levels could reflect both a reduced sensitivity of the adrenal gland to exogenous corticotropin and a decreased steroid synthesis due to a partial adrenal enzymatic defect (P450 17,20 lyase).


Subject(s)
Adrenocorticotropic Hormone/drug effects , Arthritis, Rheumatoid/physiopathology , Corticotropin-Releasing Hormone/pharmacology , Deamino Arginine Vasopressin/pharmacology , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/physiopathology , Pituitary-Adrenal System/physiopathology , Adrenocorticotropic Hormone/blood , Adrenocorticotropic Hormone/pharmacology , Adult , Animals , Cohort Studies , Dehydroepiandrosterone/blood , Dehydroepiandrosterone/metabolism , Female , Humans , Hydrocortisone/blood , Hypothalamo-Hypophyseal System/drug effects , Middle Aged , Pituitary-Adrenal Function Tests/methods , Pituitary-Adrenal System/drug effects , Reference Values , Sheep
18.
G Ital Oncol ; 10(4): 115-9, 1990.
Article in Italian | MEDLINE | ID: mdl-2093079

ABSTRACT

We made a study on patients suffering from neoplasias treated with cisplatinum to compare antiemetic efficacy of alizapride or associated to dexamethasone. We divided patients in two groups. We somministred alizapride alone to the first group and alizapride plus dexamethasone to the second one. We evaluated presence or absence of emesis, its intensity and eventual tossic effects due to the drugs through an autocompilative questionnaire given to the patients. Our results didn't show important statistical differences between the two groups, though association with dexamethasone gets better emesis control. Alizapride anyway, didn't present important collateral effects, particularly extrapyramidal ones.


Subject(s)
Antiemetics/therapeutic use , Dexamethasone/therapeutic use , Pyrrolidines/therapeutic use , Vomiting, Anticipatory/drug therapy , Antiemetics/adverse effects , Dexamethasone/adverse effects , Drug Therapy, Combination , Female , Humans , Male , Pyrrolidines/adverse effects , Random Allocation , Surveys and Questionnaires
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