A phase II, single-arm, prospective study of bendamustine plus melphalan conditioning for second autologous stem cell transplantation in de novo multiple myeloma patients through a tandem transplant strategy.

This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m(2)) as conditioning for the first ASCT. After 3-6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m(2)) and HDM (140 mg/m(2)). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients. The median number of days to neutrophil and platelet engraftment was 11 (range 9-15) and 12 (range 10-19), respectively. Only one subject experienced grade 3 diarrhea; the rate of mucositis and vomiting was significantly lower with the bendamustine plus HDM regimen compared with the HDM-only regimen (81.2 vs 96.9%, P=0.025 and 78.1 vs 100%, P=0.008). Overall response rate (ORR) was 81.2% after the first transplant, and 90.6% after the second, while complete response rates were 46.8 and 62.5%, respectively (P=0.016). Actuarial 2-year PFS and OS were 79% (95% confidence interval (CI), 60-98) and 97% (95% CI, 91-100), respectively. Bendamustine+HDM is feasible as the conditioning regimen for second ASCT in MM patients. The present study may pave the way for phase III studies specifically aimed at further investigating this combination strategy. The role of this combination in MM for conditioning regimen in a first or single ASCT setting should be also investigated.

Morphological restoration of gonadotrope population by thymulin gene therapy in nude mice.

The integrity of the thymus during the first week of life is necessary for a proper maturation of the pituitary-gonadal axis as revealed by the significantly reduced levels of circulating gonadotropins in congenitally athymic (nude) mice. In the present work we studied the impact of athymia and the effect of neonatal thymulin gene therapy on the pituitaries of adult nude mice. Also circulating thymulin and gonadotropin levels were evaluated. We used an adenoviral vector expressing a synthetic gene for the thymic peptide thymulin (metFTS) termed RAd-FTS. On postnatal day 1, each experimental heterozygous (nu/+) and homozygous (nu/nu) pup of both sexes received a single bilateral i.m. injection of RAd-FTS or RAd-GFP/TK, a control vector expressing green fluorescent protein. On postnatal days 51-52, mice were bled and sacrificed, their pituitaries were immediately dissected, fixed and immunostained. Morphometry was performed by means of an image analysis system. The following parameters were calculated: volume density (VD: cell area/reference area), cell density (CD: number of cells/reference area), and cell size (expressed in microm(2)). Serum thymulin levels were measured by a bioassay and gonadotropin levels were assayed by RIA. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and prevented the reduction in circulating gonadotropin levels. The histometrical analysis revealed that the treatment prevented the reduction in gonadotrope CD and the VD in athymic mice. Our data suggest that thymulin gene therapy may be an effective strategy to approach reproductive deficits associated with endocrine thymus dysfunction.

Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience.

Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were undergoing peripheral haematopoietic progenitor cell collection with apheresis (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most frequent short-term adverse event (71.2%). Other commonly observed short-term symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%) and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular disorders or cardiac disease occurred. Long-term follow-up included monitoring of adverse events, neoplastic disease or other pathologies. Transit ischaemic attack occurred in one donor (39 months post-donation). One autoimmune event was reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing spondylitis); one donor with a history of chronic obstructive pulmonary disease developed secondary polyglobulia (50 months post-rhG-CSF). One donor was diagnosed with lung cancer at 19 months post-donation. No haematological disease was observed. In conclusion, the short-term safety appears to be verified, whereas, although the study identified no increased risks of malignancy among HDs who received rhG-CSF, long-term safety requires more complete data sets, especially a longer follow-up and a larger number of HDs.

Clinical and economic effects of central venous catheters on oncology patient care.

Central Venous Catheters (CVC) and ports are essential devices to the medical care of cancer patients. Every year about one million CVCs are inserted in cancer patients. The field of oncohematology is making a great contribution to the development of new models of catheters and to the use of innovative materials. New therapeutic protocols, based on continuous administration and higher doses of anticancer drugs with relative phlebitis problems, have raised the issue of long CVC in situ permanence. Different complications are related to the intravascular catheters such as those associated with insertion (pneumothorax, damages to arteries and nerves), or with the duration of catheterization (thrombosis and infections). Furthermore, Catheter-Related Bloodstream Infections (CRBSI), in particular, cause significant mortality and excessive hospital costs. The aim of this prospective study was to analyze the costs related to the use of polyurethane (PU) CVC. 44 patients with a non tunneled double lumen PU CVC in place were followed for 6 months, and for each patient, time of permanence, possible antibiotic prophylaxis, blood parameters, adverse events and medical treatments were monitored. Our results suggest that physicians should pay greater attention to the correlation between new medical devices and the real benefit for the patient, and economic consequences.

Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation.

Haemopoietic stem cell therapy is an increasingly adopted procedure in the treatment of patients with malignant lymphoma. In this retrospective analysis, we evaluated 262 patients, 57 (22%) with Hodgkin's and 205 (78%) with non-Hodgkin's lymphomas (NHL), and 665 harvesting procedures in order to assess the impact of poor mobilization on survival and to determine the factors that may be predictive of CD34(+) poor mobilization. The mobilization chemotherapy regimens consisted of high-dose cyclophosphamide in 92 patients (35.1%) and a high-dose cytarabine-containing regimen (DHAP in 87 patients -(33.2%), MAD in 83 (31.7%)). The incidence of poor mobilizers (<2 x 10(6) CD34(+) cells/kg) was 17.9% overall, with a 10% of very poor mobilizers (< or = 1 x 10(6)/kg). Refractory disease status and chemotherapeutic load (>3 regimens) before mobilization played a negative role and were associated with poor mobilization. Survival analysis of all harvested patients showed an overall survival at 3 years of 71% in good mobilizers vs 33% in poor mobilizers (P=0.002). The event-free survival at 3 years was 23% in poor mobilizers and 58% in good mobilizers (P=0.04). We conclude that in NHL patients, poor mobilization status is predictive of survival.

Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats.

OBJECTIVE: To explore the effects of transient correction of enhanced corticoadrenal activity in monosodium L-glutamate (MSG)-damaged female rats on peripheral insulin sensitivity and in vitro retroperitoneal (RP) adipocyte function. DESIGNS: A dose of 4 mg/g body weight (BW) of MSG or vehicle (CTR) was i.p. injected, once every 2 days, between days 2 and 10 of age, in female rats. Intact and 21 day-operated (sham or adrenal enucleation (AE)) rats from both (CTR and MSG) groups were used for experimentation on day 120 of age. Circulating levels of several hormones, in basal and after i.v. high-glucose load conditions, and RP adiposity morphology and function were then evaluated. RESULTS: MSG rats developed increased adrenocortical function, hyperadiposity, hyperleptinemia, hyperinsulinemia and decreased peripheral insulin sensitivity. These characteristics were fully reversed after transient correction of corticoadrenal hyperactivity induced by AE. In addition, in vitro experimentation with isolated RP adipocytes indicated that cells from intact MSG animals displayed decreased sensitivity to insulin and dexamethasone stimulation of leptin secretion. Interestingly, adipocyte dysfunction in MSG rats was fully abrogated after AE-induced transient correction of insulinemia, leptinemia and adrenocortical activity. Importantly, the reversion of these metabolic abnormalities, induced by AE for 21 days, in MSG animals did occur, despite no significant changes in BW values. CONCLUSION: Our results support that the changes in adipocyte characteristics and peripheral insulin resistance, developed in this pseudo-obese female rat model, are mainly due to increased glucocorticoid production. Importantly, appropriate correction of the enhanced adrenocortical activity fully reversed these abnormal functions.

Harvesting peripheral blood progenitor cells from healthy donors with a short course of recombinant human granulocyte-colony-stimulating factor.

A short-course administration of non-glycosylated granulocyte-colony-stimulating factor (G-CSF) was investigated in 68 healthy donors (HDs) in order to collect > or = 4 x 10(6) CD34+ cells per kilogram of recipient's body weight. G-CSF was given at 10 microg/kg per day administered in two divided doses for 3 days. Leukapheresis was scheduled on day 4, 12 h after the last dose of G-CSF. A median of 35.6 circulating CD34+ cells microL(-1) (range, 3.1-185) was found on the day of leukapheresis. This allowed a median collection of CD34+ cells of 4.2 x 10(6) per kilogram of recipient's weight (range, 1.0-17.4). One single procedure was sufficient to reach the target level of CD34+ cells in 36 (53%) of 68 donors; significant correlations were found between the number of CD34+ cells collected on day 4 and the patient's sex, body-weight and volume of blood processed. A retrospective analysis was made with a historical group of HDs collected on day 5. The day 5 schedule allowed a more consistent achievement of the target cell dose with one leukapheresis (P = 0.005) and resulted in the initial collection of a significantly larger number of CD34+ cells (P = 0.006).

Histomorphological and quantitative immunohistochemical changes in the rat pancreas during aging.

Although the endocrine pancreas is the purpose of several deep investigations, morphological data referred to the effect of aging on the gland are not homogeneous. The purpose of the current work was to analyze the changes occurring in the pancreas of aged rats, with especial reference to the islet cell populations. Six young (Y), old (O) and senescent (S) male Sprague-Dawley rats were used. The pancreas tails were processed for light microscopy and studied by means of routine stains as well as by immunohistochemical identification of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide- secreting cells (Dako Envision System, DAB as chromogen). A progressive pancreatic histoarchitecture distortion was found among the aged animals. Even when the alterations were not uniformly observed, they appeared more evident and severe in the S group. The S rats showed significantly increased volume density and cell density of the B cell population, as well as larger number of islet profiles, when compared to O rats. A significant progressive increment of adipose tissue was also evident in aged animals. No abnormal changes were detected in the non-B cell populations of the different groups. The quantitative changes found in aged animals suggest a possible compensatory reaction of the B cell population in an attempt to curb the influence of diabetogenic factors mounting with advanced age.

Histomorphological and quantitative immunohistochemical changes in the rat pancreas during aging

Although the endocrine pancreas is the purpose of several deep investigations, morphological data referred to the effect of aging on the gland are not homogeneous. The purpose of the current work was to analyze the changes occurring in the pancreas of aged rats, with especial reference to the islet cell populations. Six young (Y), old (O) and senescent (S) male Sprague-Dawley rats were used. The pancreas tails were processed for light microscopy and studied by means of routine stains as well as by immunohistochemical identification of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide- secreting cells (Dako Envision System, DAB as chromogen). A progressive pancreatic histoarchitecture distortion was found among the aged animals. Even when the alterations were not uniformly observed, they appeared more evident and severe in the S group. The S rats showed significantly increased volume density and cell density of the B cell population, as well as larger number of islet profiles, when compared to O rats. A significant progressive increment of adipose tissue was also evident in aged animals. No abnormal changes were detected in the non.B cell populations of the different groups.

Glucocorticoid-induced apoptosis in lymphoid organs is associated with a delayed increase in circulating deoxyribonucleic acid.

Pathological processes like cancer, chronic inflammation and autoimmune phenomena, all of which involve massive cell death, are associated with significant increases in circulating DNA. In order to clarify whether massive apoptosis occurring under physiological circumstances also causes DNA release into the circulation, we correlated the time-course of dexamethasone-induced intra thymic cell apoptosis with plasma DNA dynamics in rats. Animals were given 10 mg/l dexamethasone in their drinking water for up to 7 days. Sequential plasma samples were obtained during the treatment and DNA was quantitated by a micro fluorometric assay. Thymus and spleen weight as well as apoptotic cell levels were assessed at different times. Seven days of glucocorticoid treatment reduced thymic and spleen mass by 82 and 31%, respectively. Intra thymic apoptosis was maximal 24 h after the beginning of glucocorticoid treatment, declining markedly by 48 h. Very little apoptosis was observed in the spleen. Plasma DNA increased steadily during the first 4 days of glucocorticoid treatment (11.8 +/- 1.2 microg/ml on day 0; 24.2 +/- 1.6 microg/ml on day 4) beginning to decline afterward. Thymectomy but not splenectomy, drastically reduced the glucocorticoid-induced increase in plasma DNA. It is concluded that hormone-induced massive intra thymic cell death is followed by a delayed release of nucleosomal DNA into the circulation.

Hypoxic stop-flow perfusion with mitomycin-C in the treatment of multifocal liver metastases. Usefulness of a vascular arterial stent to prevent iatrogenic lesions of the hepatic arterial wall.

13 patients affected by multifocal and/or large liver metastases from various solid tumors have been treated with stop-flow liver perfusion, to evaluate the safety and feasibility of hypoxic loco-regional infusion with Mitomycin C. The treatment was based on the hypoxic effect due to stop-flow, potentiating the cytotoxic activity of Mitomycin C, combined with the ischemic damage caused by the embolization of the vascular supply to the tumor. The schedule consisted in blocking arterial flow by an angiographic occlusion balloon catheter inflated in the hepatic artery, with previous placement of a vascular stent in order to prevent iatrogenic arterial lesions, and followed by the intraarterial administration of Mitomycin C; finally, arterial hepatic embolization was performed by a gelatine sponge. The study is ongoing with a median follow up of 8 months (range 2-12). Partial response was observed in 1/13 patients (8%), stable disease in 8/13 patients (61%), while progressive disease occurred in 4/13 patients (31%). Nine patients are still alive, and four patients died for hepatic progressive disease, three of them heavily pre-treated with multiple lines of chemotherapy for advanced disease. Toxicity was mild; main side effects were anaemia and thrombocytopenia(Grade 3 both in 1/15 treatments), while fever, nausea and vomiting and upper abdominal pain were short-lasting and easily manageable. No iatrogenic lesion of the hepatic arterial wall occurred. These preliminary data, although the small number of patients and the short follow up, show that the procedure is safe and feasible, with a interesting percentage of clinical responses. In addition, the placement of an arterial stent have demonstrated to protect vascular wall ensuring a regular blood flow, so allowing to perform repeated treatments in responsive patients. The good tolerability of this therapeutic modality suggests further investigation in order to determine its efficacy even in combination with systemic chemotherapy and other locoregional treatments such as termoablative procedures and/or intraarterial antiblastic perfusions in patients affected by metastatic liver disease.

Systemic aspergillosis in a patient with non-Hodgkin's lymphoma developing acute graft-versus-host disease after autologous peripheral blood stem cell transplantation.

Graft-versus-host disease (GVHD) is rare in the autologous setting. We describe a non-Hodgkin's lymphoma case developing acute GVHD after autologous peripheral blood stem cell transplantation following several lines of chemotherapy inclusive of fludarabine. At day +33, he complained of fever, diffused erythematous papulosis with ulceration of skin lesions. A punch biopsy indicated a grade III GVHD. A dose escalation of corticosteroids, cyclosporin-A and photoapheresis induced a transient response. He developed positivity to CMV and systemic aspergillosis. He died at day +185 in haematological complete remission, despite infection-oriented treatment. In spite of the use of prophylactic immunosuppressive drugs, between 50% and 70% of patients given HLA-identical marrow graft develop acute graft-versus-host disease (GVHD) that, in turn, significantly increases the risk of transplant-related mortality. Autologous BMT has been shown to be an effective procedure in several malignancies, persistently becoming a first-line choice in treating patients affected with lymphoproliferative disorders, specially non-Hodgkin's lymphoma (NHL). Although GVHD is a very rare event in the autologous setting (AuGVHD), a consistent number of reports dealing with GVHD-like phenomena has emerged, especially in breast cancer patients. More often, AuGVHD has been induced by the use of immunosuppressive agents, such as cyclosporin-A (CSA), in attempt to evoke a graft-versus-tumor (GVT) effect. However, AuGVHD is mild and self-limited phenomenon. We report the case of a NHL patient who developed unresponsive GVHD after autologous peripheral blood stem cell transplantation (PBSCT). Because of the immunosuppressive therapies, he developed systemic aspergillosis. He died in haematological complete remission despite infection-oriented treatment.

Ultrastructural and quantitative immunohistochemical changes induced by nonsteroid antiandrogens on pituitary gonadotroph population of prepubertal male rats.

Specific blockade of the androgen receptor by the nonsteroid antiandrogens flutamide and Casodex has proven to be a useful tool for studying androgens in vivo. The aim of the present study was to investigate the effect of antiandrogen administration at the pituitary level by evaluating the ultrastructural changes in gonadotrophs, in correlation with the quantitative immunohistochemical findings, and by comparing these alterations with the effect of androgen deprivation by castration either with or without subsequent androgen replacement. Male Sprague-Dawley rats (23 days old) were grouped as follows: (1) controls, (2) flutamide-injected (10 mg/rat/day), (3) Casodex-injected (10 mg/rat/day), (4) castrated, and (5) castrated plus androgen-replaced (dihydrotestosterone propionate; 40 microg/rat/day). Groups were sacrificed after 10 days of maintenance under each condition. Pituitaries were processed for both light and electron microscopy. Serial sections (4 microm) were obtained at different levels and immunostained by means of the primary murine monoclonal antibodies anti-FSH and anti-LH and a peroxidase-mediated EnVision System (Dako). Volume density, cell density and mean cell area were measured with an image analysis system (Imaging Technology, Software Optimas 5.2). The mean cell area (p < 0.001) and the volume density (p < 0.05) increased significantly in the flutamide- and Casodex-treated groups as well as the castrated group of FSH and LH cells. On the other hand, androgen replacement in the castrated rats, however, reduced in both parameters related to control animals. The cell density of FSH-secreting cells was increased (p < 0.05) in the Casodex and flutamide treatment as well as castrated group. The cell density of LH-secreting cells was augmented (p < 0.05) in the Casodex-treated group, while there was no increase in such parameter with flutamide and castration. The ultrastructure of all groups showed two types of gonadotrophs. Type I cells contained large (300-500 nm) and small (150-200 nm) secretory granules, while type II cells were smaller, and exhibited only small granules (100-200 nm). Flutamide-treated, Casodex-treated and castrated groups presented a decreased number of secretory granules with some exocytotic profiles, well-developed rough endoplasmic reticulum and an expanded Golgi complex of both types of cells. The gonadotrophs from the castrated group exhibited numerous mitochondria with electron-dense ring-shaped laminar figures, while in the castrated plus androgen-replaced rats only a few mitochondria had similar changes to those observed in castrated animals, as a possible residual alteration. Finally, the gonadotrophs from flutamide-treated rats showed mitochondrial alterations with clear areas and isolated electron-dense laminar figures. In summary, we conclude that lack of androgen reaction through the effects of nonsteroid antiandrogens and castration on prepubertal rats produced a hypertrophia-hyperplasia of the FSH cells, and hypertrophia of LH-secreting cells, with marked alterations at the ultrastructural level suggestive of a hyperstimulation stage.

Morphometric and ultrastructural analysis of different pituitary cell populations in undernourished monkeys

Undernutrition elicited by a low-protein diet determines a marked reduction of hypophyseal activity and affects the function of the respective target organs. The objective of the present investigation was to study the ultrastructural and quantitative immunohistochemical changes of the different pituitary cell populations in undernourished monkeys that had been previously shown to have significant changes in craniofacial growth. Twenty Saimiri sciureus boliviensis monkeys of both sexes were used. The animals were born in captivity and were separated into two groups at one year of age, i.e., control and undernourished animals. The monkeys were fed ad libitum a 20 percent (control group) and a 10 percent (experimental group) protein diet for two years. Pituitaries were processed for light and electron microscopy. The former was immunolabeled with anti-GH, -PRL, -LH, -FSH, -ACTH, and -TSH sera. Volume density and cell density were measured using an image analyzer. Quantitative immunohistochemistry revealed a decrease in these parameters with regard to somatotrophs, lactotrophs, gonadotrophs and thyrotrophs from undernourished animals compared to control ones. In these populations, the ultrastructural study showed changes suggesting compensatory hyperfunction. On the contrary, no significant changes were found in the morphometric parameters or the ultrastructure of the corticotroph population. We conclude that in undernourished monkeys the somatotroph, lactotroph, gonadotroph, and thyrotroph cell populations showed quantitative immunohistochemical changes that can be correlated with ultrastructural findings

Infectious complications in breast cancer patients undergoing peripheral blood stem cell transplantation: a single center retrospective analysis towards outpatient strategy.

Infectious complications were retrospectively analyzed in 129 transplants, performed in 90 patients, to identify characteristics that qualify breast cancer patients for outpatient-based PBSCT. Thirty-one cases (24%) did not develop fever. Of the remaining 98 cases, 84.7% developed fever during severe neutropenia. On univariate analysis, disease stages II-III, first PBSCT, mucositis grades II-IV and the use of two alkylators were associated with a higher risk of fever development. The latter two factors also affected fever occurrence on multivariate analysis. A longer median time to fever onset was observed in patients conditioned with single as compared to double alkylating agent-containing regimens (respectively 8th vs 6th day, P < 0.00001). As compared with metastatic breast cancer (MBC), high risk breast cancer showed a 2.3-fold increased risk of developing early fever during neutropenia (CI 2.3-3.8), remaining the only variable still significant on multivariate analysis (P = 0.0039). Combination antibiotic therapy was equivalent to single agent therapy. Patients suffering from microbiologically documented fever were at higher risk of undergoing second-line antibiotic therapy. In conclusion, MBC patients treated with a conditioning regimen containing only one alkylating agent and adequate prophylaxis for mucositis may qualify for outpatient-based PBSCT on the basis of a lower risk of infection.

Immunohistochemical and ultrastructural study of pituitary folliculostellate cells during aging in rats.

The impact of aging on pituitary folliculostellate (FS) cells is not well known. The aim of the work reported here was to carry out a quantitative immunohistochemical assessment of the FS population in male and female rats during aging and to correlate the findings with possible changes at the ultrastructural level. Young (4 months), old (20 months) and senescent (29 months) Sprague-Dawley rats of both sexes were sacrificed by rapid decapitation, their pituitaries dissected and processed by both light immunohistochemistry and electron microscopy. Serial sections (4 microm) were obtained at different levels and immunostained by means of rabbit anti-S100 serum as the primary antibody and a peroxidase-mediated EnVision System (Dako). Measurement of volume density (VD) and cell density (CD) was made in S100-reacting elements by means of an image analysis system (Imaging Technology, Optimas). These parameters were found to be significantly (p < 0.05) decreased in old and senescent rats as compared to young animals. In senescent females, which presented a high incidence of microprolactinomas, a significant (p < 0.01) increment of VD and CD was observed in FS cells in the area surrounding the adenomas, together with a marked decrease in those parameters within the tumors. Sexual dimorphism was not found except for the prolactinoma-bearing female group. The ultrastructure of FS cells showed the typical characteristics previously described in the pituitary gland. Only moderate changes in the endoplasmic reticulum were observed in old and senescent animals. We conclude that aging has a clear effect on the morphology of the pituitary FS cell population.

Immunohistochemical and ultrastructural age-related changes in rat lactotroph cells

Ageing produces alterations in some functions of the hypothalamo-pituitary axis leading to sexually dimorphic changes in the prolactin (PRL)-secreting cells. Since quantitative morphological data of these age-associated alterations are scarce, we carried out a morphometric immunohistochemical assessment as well as an ultrastructural study of the PRL cell population in male and female rats of different ages. Young (3-month-old), old (20-month-old), and senescent (31-month-old) Sprague-Dawley rats of both sexes were sacrificed by rapid decapitation, their pituitaries immediately dissected out and processed for both immunohistochemistry and electron microscopy. Analysis of different morphometric parameters revealed that the cell density (CD) and volume density (VD) significantly decreased with age in male rats. In females, while CD showed a significant age-related diminution when young rats were compared to old ones, this parameter increased in senescent animals. The VD presented higher values in senescent rats. When the data were compared between sexes, VD was found to be higher in females if old and senescent rats were considered. Finally, CD increased significantly in females when compared to males. The ultrastructure of the PRL cells from old and senescent animals of both sexes exhibited changes suggestive of an hyperstimulation state, with some prolactotrophs having the appearance of cells undergoing an involutive process. We conclude that ageing has a differential impact on the PRL cells of male and female rats with respect to the immunohistochemical and ultrastructural features of that cell population