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D Pignatelli

Publications and source records attributed to D Pignatelli.

At least 19 recordsLinked to original sources
PubMed2006

Reproductive outcome of women with 21-hydroxylase-deficient nonclassic adrenal hyperplasia.

CONTEXT: Because many women with 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) carry at least one allele affected by a severe mutation of CYP21, they are at risk for giving birth to infants with classic adrenal hyperplasia (CAH). OBJECTIVE: Our objective was to determine the frequency of CAH and NCAH infants born to mothers with 21-OH-deficient NCAH. DESIGN AND SETTING: We conducted an international multicenter retrospective/prospective study. PATIENTS AND METHODS: The outcome of 203 pregnancies among 101 women with 21-OH-deficient NCAH was reviewed. The diagnosis of 21-OH-deficient NCAH was established by a basal or post-ACTH-stimulation 17-hydroxyprogesterone level of more than 10 ng/ml (30.3 nmol/liter). When possible, genotype analyses were performed to confirm CAH or NCAH in the offspring. RESULTS: Of the 203 pregnancies, 138 (68%) occurred before the mother's diagnosis of NCAH and 65 (32%) after the diagnosis. Spontaneous miscarriages occurred in 35 of 138 pregnancies (25.4%) before the maternal diagnosis of NCAH, and in only four of 65 pregnancies (6.2%) after the diagnosis (P < 0.002). Four (2.5%; 95% confidence interval, 0.7-6.2%) of the 162 live births were diagnosed with CAH. To date, 24 (14.8%; 95% confidence interval, 9.0-20.6%) children, 13 girls and 11 boys, have been diagnosed with NCAH. The distribution of NCAH children and their mothers varied significantly by ethnicity (P < 0.0001, for both). CONCLUSIONS: The risk of a mother with 21-OH-deficient NCAH for giving birth to a child affected with CAH is 2.5%; at least 14.8% of children born to these mothers have NCAH.

Adrenal Hyperplasia, Congenital↗
PubMed2004

ACTH modulates ERK phosphorylation in the adrenal gland in a time-dependent manner.

ACTH is known to act through the activation of cAMP/PKA in adrenocortical cells, but it has been suggested that it could also act via other pathways such as the ERK 1/2 cascade. To determine the effects of ACTH administration at sequential time points on the activation of ERKs 1/2, groups of rats (n = 6/group) were subjected to i.p. injections of either ACTH (Synacthen Depot-0.2 mg/Kg), or saline (Ct). The animals were sacrificed and the adrenal glands collected at different timings after ACTH injection (2 h, 18 h and 24 h). Two additional groups were injected daily until sacrifice (3 days and 15 days). Blood was collected for analysis and the adrenals were used for immunohistochemistry or Western Blot (WB) analysis. Immunoreactivity was scored by counting the mean number of zonae fasciculata (ZF) and reticularis (ZR) positive cells/section (mean +/- SEM). Adrenal weight was increased by ACTH in comparison with Ct. Corticosterone levels, as expected, were higher in ACTH treated animals than in Ct. The number of pERK positive cells increased in a time-dependent manner until 3d, and declined although not significantly in the 15 days animals (Control--48.13 +/- 9.0; ACTH 2 h--125.93 +/- 14.5; ACTH 18 h-139.46 +/- 10.0; ACTH 24 h--185.28 +/- 13.3; ACTH 3 days--198.47 +/- 18.6; ACTH 15 days--158.58 +/- 15.1). Comparable results were obtained with WB analysis. Our data shows that ACTH induces the activation of the MAPK/ERKs 1/2 cascade, especially in the ZF, consistent with this zone being more responsive to ACTH.

Adrenal Glands↗
PubMed2002

Proliferation of capsular stem cells induced by ACTH in the rat adrenal cortex.

Despite great efforts devoted to clarifying the localization of proliferative activity in the adrenal cortex, the agents that stimulate proliferation remain controversial, and the nature of the stem cells from which cortical cells differentiate is incompletely understood. We studied proliferative activity in the rat adrenal cortex using an immunohistochemical method to detect the presence of the Proliferating Cell Nuclear Antigen (PCNA) (an intranuclear enzyme whose synthesis reaches the maximum intensity during the S-phase of the cell cycle). Groups of six rats were subjected to daily intraperitoneal injection of either corticotropin (ACTH1-24--0.2 mg/kg), dexamethasone (Dexa--4 mg/kg) or 0.9% saline for three consecutive days and killed 24 h after the last injection. Adrenal weight was significantly increased by ACTH treatment and reduced by Dexa. Concentrations of endogenous ACTH in plasma were lower in the Dexa group than in controls, and curiously, this was true in the ACTH1-24 treated group as well, probably in consequence of the increased corticosterone levels providing negative feedback at the hypothalamic-pituitary level. Corticosterone levels, as expected, were increased by the ACTH stimulus and reduced by the use of Dexa. Proliferating cell nuclear antigen immunostaining was close to zero in Dexa treated animals and low in controls. In ACTH treated rats, a significantly increased number of cells were positively stained. Positive cells were identified in both in zona glomerulosa (ZG) and zona intermedia (ZI) but many were located in the capsule. Zona fasciculata (ZF) and zona reticularis (ZR) were devoid of staining in all of these cases. We conclude that pharmacological doses of ACTH induce proliferation of capsular fibroblasts. Following descriptions by early 20th century researchers it is possible that these cells may also be stem cells and differentiate into adrenal cortex cells.

Adrenal Cortex↗
PubMed2000

21-Hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study.

OBJECTIVE: Our aim was to determine whether the clinical features of 21-hydroxylase-deficient nonclassic adrenal hyperplasia are correlated with either age at symptom onset or age at presentation, or both, and with the degree of adrenocortical abnormality. STUDY DESIGN: In a multicenter cohort design 220 women with nonclassic adrenal hyperplasia, with a basal or adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone level >30.3 nmol/L, were studied, either prospectively (n = 39) or retrospectively (n = 181). Patients were stratified by age of presentation into 5 groups: (1) <10 years (n = 25), (2) 10 to 19 years (n = 64), (3) 20 to 29 years (n = 83), (4) 30 to 39 years (n = 30), and (5) 40 to 49 years (n = 16). Two patients >50 years old were excluded from the analysis because of age. RESULTS: Ninety-two percent of patients <10 years old had premature pubarche at presentation, whereas clitoromegaly and acne were each present in only 20% of these younger subjects. With only patients > or =10 years old considered, presenting clinical features included hirsutism (59%), oligomenorrhea (54%), acne (33%), infertility (13%), clitoromegaly (10%), alopecia (8%), primary amenorrhea (4%), and premature pubarche (4%). Among the patients >/=10 years old, the prevalence but not the degree of hirsutism increased significantly with age. Basal levels of 17-hydroxyprogesterone in adolescents were significantly higher than the levels found either in children (<10 years old) or women 40 to 49 years old (P <.01 and P <.03, respectively), although no difference was noted in the stimulated 17-hydroxyprogesterone levels between age groups. The adrenocorticotropic hormone-stimulated levels but not the basal levels of 17-hydroxyprogesterone were significantly higher in patients with clitoromegaly than in women without clitoromegaly. Alternatively, there were no differences in either basal or stimulated 17-hydroxyprogesterone levels between patients with and those without hirsutism, acne, or alopecia. CONCLUSION: In children <10 years old the most common presenting complaint was premature pubarche, whereas hirsutism and oligomenorrhea were more common in older patients. The prevalence of hirsutism increased with age, suggesting the progressive nature of nonclassic adrenal hyperplasia. Furthermore, the adrenocorticotropic hormone-stimulated levels of 17-hydroxyprogesterone were higher in patients with clitoromegaly, which suggests that the degree of adrenocortical dysfunction in nonclassic adrenal hyperplasia determines, at least in part, the clinical presentation.

17-alpha-Hydroxyprogesterone↗
PubMed2000

Chronic stress effects on the rat adrenal cortex.

Under the influence of a chronic permanent stress, the adrenal function as well as the entire hypothalamic-pituitary-adrenal axis (HPAA) suffered an adaptation process that resulted in the normalization of the studied stress hormones (ACTH, corticosterone and aldosterone) with the exception of plasma renin activity which first diminished and at the end increased. ACTH receptors exhibited a dual response since after 14 days of permanent stress MC2-R showed a slight reduction while MC5-R was still up-regulated.

Adrenal Cortex↗
PubMed1999

Ontogeny of 3beta-hydroxysteroid dehydrogenase expression in the rat adrenal gland as studied by immunohistochemistry.

The enzyme 3beta-hydroxysteroid dehydrogenase plays a crucial role in the steroidogenic process in the adrenal gland. In the present study we tried to characterize its localization and developmental changes in the rat adrenal cortex during the postnatal period, using immunohistochemical methods. The development of the different zones evidenced specific particularities: the zona glomerulosa almost lacked 3beta-HSD in the first days after birth; then, 3beta-HSD increased, attaining a maximum around day 20 and afterwards it decreased again and remained less intense than the neighbouring zona fasciculata up until adulthood (65 days of age). The zona fasciculata was already intensely stained at birth and the expression of 3beta-HSD increased rapidly reaching a maximum after 2 weeks of life and that level was maintained from then on. The inner part of the zona fasciculata and the zona reticularis both of which develop postnatally were faintly immunostained before day 20. The expression of 3beta-HSD increased after that age to become approximately as intense as in the outer zona fasciculata and so remaining until day 90. The development of the zona glomerulosa was parallel to the secretion of aldosterone. The same did not occur with the zona fasciculata as the intensity of staining during the first 14 postnatal days was accompanied by very low levels of corticosterone.

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

Effects of prolonged infusion of basic fibroblast growth factor and IGF-I on adrenocortical differentiation in the autotransplanted adrenal: an immunohistochemical study.

Adrenocortical regeneration after adrenal autotransplantation provides a model for the study of local autocrine/paracrine mechanisms involved in the growth and differentiation of the adrenal cortex. To study the possible involvement of some growth factors, namely basic fibroblast growth factor (bFGF, FGF-2) and insulin-like growth factor I (IGF-I), in cell differentiation, immunohistochemical and ultrastructural studies were carried out on adrenal autotransplants in adult male rats. To distinguish between fasciculata and glomerulosa-like cells with accuracy, tissue sections were immunostained with IZAb, which recognizes the inner zone antigen (IZAg) present in fasciculata and reticularis cells but absent from the glomerulosa, and by electron microscopy. IGF-I-treated animals exhibited a clear glomerulosa-like zone that was devoid of IZAb immunostaining. In this outer subcapsular area, ultrastructural examination showed cells containing mitochondria with irregular cristae resembling those of the fetal or immature glomerulosa cells. In contrast, no significant morphological differences were observed in bFGF-treated animals when compared with those from saline-treated controls, in both of which, IZAb immunostaining occurred in almost all adrenocortical cells, with no clear zonation or glomerulosa, as seen in the intact animal. Plasma aldosterone and corticosterone concentrations were lower in autotransplanted control animals than in intact controls, although plasma renin activities were similar. IGF-I treatment significantly increased aldosterone concentrations, whereas corticosterone and plasma renin activity were reduced. bFGF infusion further reduced plasma aldosterone, although plasma renin activity and corticosterone were unaffected. These results suggest that the two growth factors have different effects on zonal differentiation and function in the autotransplanted gland. In particular, bFGF, by reducing glomerulosa function, appears partly to replicate the actions of ACTH in normal animals. In contrast, IGF-I enhances the glomerulosa secreting phenotype and diminishes that of the fasciculata/reticularis, possibly replicating the actions of angiotensin II or a low sodium diet.

Adrenal Cortex↗
PubMed1998

The development of the adrenal gland zona glomerulosa in the rat. A morphological, immunohistochemical and biochemical study.

We have studied the development of the adrenal gland in the rat comprising the ages ranging from 0 to 90 days after birth. The weight of the animals and that of the adrenal glands demonstrated a linear growth with time until 75 days, both in males and females. The area of the zona glomerulosa (ZG) increased in size from birth until approximately 40 days of age. After that, growth had a much smaller slope (females, r=0.84, P < 0.001; males, r=0.81, P < 0.001). Aldosterone secretion had a marked increase until 20 days of age and thereafter demonstrated a tendency for a decrease (females, r=-0.19, P < 0.02: males r=-0.26, P < 0.001). Plasma renin activity followed a trend parallel to that of aldosterone. The steroid precursor 18-OH-deoxycorticosterone (18-OH-DOC) demonstrated a different course as it increased progressively with age especially in the females (females, r=0.57, P < 0.001; males, r=0.40, P <0.001). The expression of the enzyme 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) was also studied by immunohistochemistry and it was shown to be very low at birth and starting to increase by 10 days of age. After 30/40 days of age the amount of this enzyme existing in the ZG was comparable with that of the outer zona fasciculata (ZF). We conclude that the development of the ZG in the rat has particularities that make it different from that of the rest of the cortex.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Adrenal incidentalomas: adrenal hemangioma in a patient with congenital adrenal hyperplasia.

We describe a case of an adrenal incidentalomas in the setting of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The adrenal mass was shown to be a cavernous hemangioma. Such neoplasms are rare but have the risk of retroperitoneal hemorrhage and may be difficult to differentiate from malignant adrenal tumors. The main consideration brought up by this case was that the simultaneous occurrence of an endocrinologically active disease such as CAH in association with a likely incidentalomas may lead to surgical intervention, due to the impossibility of being certain of its nonsecretory nature. Laparoscopic adrenalectomy allowed safe resection with no morbidity and a short hospitalization.

Adrenal Gland Neoplasms↗
PubMed1996

Acute stress effects on the adrenal cortex in the rat. A biochemical and immunohistochemical study.

Activation of the stress system induces physiologic alterations as well as behavioural ones that ultimately improve the adaptability of the organism to adverse conditions. In our previous study on the morpho-functional evolution of the adrenal cortex, from birth to adulthood, the question of what could be the contribution of immobilization stress to the observed hormonal levels was brought up. Male adult rats were submitted to immobilization of variable duration. The antibody IZAb was used to allow a correct differentiation between the zona glomerulosa (ZG) and the inner zones of the cortex (IZ). A significant increase of the ACTH levels, especially at 5 and 30 min was observed. Corticosterone (B), surprisingly, revealed 2 peaks of secretion: one at 30 sec and another at 30 min. The area of the cortex, determined by an image analyser, only showed a slight decrease at 30 sec. The proportions of the cortical area occupied by ZG and IZ were unaltered. We concluded that a corticosterone peak at 30 sec precedes the elevation of ACTH induced by stress. Only the second peak, in view of its parallel course to ACTH, can be attributed to an effect of this pituitary hormone.

18-Hydroxydesoxycorticosterone↗
PubMed1996

New insights into zonal differentiation of adrenal autotransplants in the rat: an immunohistochemical study.

Adrenal gland autotransplantation, an interesting model of adrenal regeneration, provides the reconstruction of distinct functional and morphological zonae. An immunohistochemical study of the adrenal gland of adult male rats after autotransplantation and endothelin-1 (ET-1) stimulation was carried out. The technique involved total adrenalectomy and immediate autotransplantation of small adrenal pieces under the skin of the dorsal region. The animals were killed 90 days after the autotransplantation and 1 h after intravenous ET-1 administration. Sections of recovered adrenal grafts were incubated with IZAb, a monoclonal antibody which interacts with an antigen (IZAg) predominantly found in rat adrenal inner zones. Saline-treated control autotransplanted animals showed IZAb immunostaining in almost all adrenocortical tissue, with the exception of small clusters of cells beneath the capsule. ET-1-treated animals exhibited an extended zone devoid of immunostaining and located in the subcapsular area. In addition, ET-1-stimulated animals showed significant increases in aldosterone as well as corticosterone concentrations in plasma. These results revealed that ET-1 stimulated the development of an extended subcapsular zone lacking IZAg expression, an effect that suggests its role in zona glomerulosa induction in these animals.

Adrenal Glands↗
PubMed1994

Unilateral adrenal hyperplasia.

A case of unilateral primary adrenal hyperplasia, without concomitant hypokalemia, is presented. After surgical removal of the gland, a complete remission occurred. This rare condition may, in fact, be more frequent than thought as it can coexist with normokalemia. We postulate that it is probably a new phase of the transformation between hyperplasia and adenomas that can also occur in the adrenal cortex similar to such transformations in other endocrine organs.

Adenoma↗
PubMed1994

[The risk of diabetes mellitus in relatives of diabetics treated with insulin].

The objective of this study was to compare the risk of diabetes mellitus in the relatives of type 1 (defined as cases diagnosed before 40 years and beginning insulin less than two years later) and in those of type 2 diabetics, treated with insulin. A random sample of 303 patients was obtained from responders to a postal survey sent to all 2800 diabetics living in the Oporto self county and identified as users of insulin the injection pen. After selecting those who completed the questions for sex, age, dates of diabetes diagnosis and of first insulin prescription, we were left with 192 index cases. They provided data concerning sex; age, and presence of diabetes for 1370 relatives (parents, siblings, offspring and spouses). The risk of diabetes (unspecified type) in family members was significantly lower in relatives of type 1 diabetics (OR = 0.31, CI 95%:0.19-0.48, p < 0.0005). This family risk was lower when the index case was a male (OR = 0.24, CI 95%:0.12-0.47 vs OR = 0.39, CI 95%:0.21-0.74) or for female relatives (OR = 0.22, CI 95%:0.11-0.42 vs OR = 0.43, CI 95%:0.22.-0.82). After adjustment for confounders applying logistic regression to each family stratum, the risk remained significantly lower for parents (OR = 0.35, CI 95%:0.17-0.71) and siblings of type 1 diabetics compared to similar relatives of type 2 cases (OR = 0.84, CI 95%:0.06-10.6) but was not significantly different for the offspring (OR = 0.68, CI 95%:0.11-4.17) or the spouses (OR = 0.84, CI 95%:0.06-10.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Amitosis in human adrenal cells.

Adrenal pieces obtained from 3 female and 2 male patients showed morphological figures of amitosis in adrenal zona reticularis cells. Such aspects were observed in both normal and hyperactive adrenals. Nuclei appeared constricted, heavily stained, with coarse chromatin, sometimes scattered among cytoplasmic organelles, but never marginating in crescentic caps. Cleavage of the cells originated two halves with a nucleolus in each pole. Binucleated cells were also seen in zona reticularis. The meaning of amitosis in human adrenal is discussed.

Adolescent↗
PubMed1989

Postnatal maturation of primary afferent terminations in the substantia gelatinosa of the rat spinal cord. An electron microscopic study.

Axodendritic dark sinuous endings occurred on the day of birth (PO) in the synaptic areas of lamina II. These terminals (TI) turned very electron dense and shrunken after capsaicin administration. From day P2, TI-terminals exhibited fluoride-resistant acid phosphatase (FRAP) reactivity. Such findings revealed their origin from primary afferent fine fibers. Dark scalloped, FRAP-reactive, central terminals of type I glomeruli (CI) were first observed on P5. During the ensuing survival times up to P20 an increasing number of CI-terminals seemed to evolve from the less mature TI-endings that gradually disappeared. A few large clear boutons, similar to the central terminals of type II glomeruli (CII) of the adult which arise from thick afferents, were also present in deep lamina II on the day of birth and became more numerous thereafter. From P5, both CI- and CII-endings developed pre- and postsynaptic contacts with vesicle-containing profiles though it was sometimes difficult to distinguish the axonic (V2) from the dendritic (V1-presynaptic dendritic) profiles. CI-boutons established as many presynaptic as postsynaptic contacts with vesicle-containing profiles. In contrast, CII-terminals were mostly postsynaptic to vesicle-containing profiles. Thus, the boutons generated by thin (CI-boutons) and thick (CII-boutons) primary axons gradually develop synapses with vesicle-containing profiles probably arising from local interneurons. The resulting pre- and/or postsynaptic interactions may contribute to the physiological maturation of somatosensory integration that occurs postnatally.

Acid Phosphatase↗
PubMed1986

Rexed's laminae and the acid phosphatase (FRAP)-band in the superficial dorsal horn of the neonatal rat spinal cord.

The pattern of Rexed's lamination and the situation of the FRAP-reactive band in the superficial dorsal horn were studied in transverse sections of the cervical cord of the rat from the day of birth (P0) to postnatal day P20. Laminae I, II and III increased moderately in thickness during this period, but the outer (IIo) and inner (IIi) zones of lamina II underwent opposite evolutions. Lamina IIi nearly doubled in thickness while lamina IIo decreased markedly. The FRAP-band was large on days P2 and P5 virtually covering lamina IIi, then shrank to a thinner strip in its dorsal part. It is suggested that lamina IIi growth is due to the massive arrival of FRAP-reactive thin primary axons followed by large afferents from deep layers occurring during the postnatal period, and the subsequent establishment of synaptic connections with the developing dendritic trees of dorsal horn cells.

Acid Phosphatase↗