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A genetic framework for fruit patterning in Arabidopsis thaliana.

In the model plant Arabidopsis thaliana, the establishment of organ polarity leads to the expression of FILAMENTOUS FLOWER (FIL) and YABBY3 (YAB3) on one side of an organ. One important question that has remained unanswered is how does this positional information lead to the correct spatial activation of genes controlling tissue identity? We provide the first functional link between polarity establishment and the regulation of tissue identity by showing that FIL and YAB3 control the non-overlapping expression patterns of FRUITFULL (FUL) and SHATTERPROOF (SHP), genes necessary to form stripes of valve margin tissue that allow the fruit to shatter along two defined borders and disperse the seeds. FIL and YAB3 activate FUL and SHP redundantly with JAGGED (JAG), a gene that also promotes growth in organs, indicating that several pathways converge to regulate these genes. These activities are negatively regulated by REPLUMLESS (RPL), which divides FIL/JAG activity, creating two distinct stripes of valve margin.

Arabidopsis↗

Transcriptional analysis of Marek's disease virus (MDV) genes in MDV-transformed lymphoblastoid cell lines without MDV-activated cells.

Spontaneously activated MDV is rarely included in MDV-transformed cells, while it may influence the results of transcriptional analysis. A population consisting of 10(3) MDV-transformed cells probably did not include spontaneously activated MDV, since the estimated frequency of MDV-transformed cells including activated MDV was below 0.01% according to limiting-dilution polymerase chain reaction (PCR) and the presence of the major early antigen pp38 in 6 transformed cell lines. Reverse transcriptase-PCR (RT-PCR) products corresponding to ICP27, pol, TK, US3, A41, gA, gB and UL50 genes were undetectable in 10(3) cells by Southern hybridization of the RT-PCR products. Transcripts of the VP16 and SORF2 genes were detected in the 10(3) cells of MSB-1, and the pp14 gene transcript was found in 10(3) cells of RPL-1 but not in 10(3) cells of HPRS-1, MOGA-2, MSB-1 or MTB-1. A transcript corresponding to the ICP4 sequence was detected as a 0.7 kbp RT-PCR product in 10(3) cells of these MDV cell lines but not in the retrovirus-transformed 1104B1 cell line. The transcript corresponding to the 0.7 kbp RT-PCR product suggested a splice by its size and sequence. Thus, transcriptional analysis of 10(3) MDV-transformed cells revealed that the transcript corresponding to the ICP4 sequence was a common transcript in latently infected MDV-transformed cells, while most of the genes did not transcribe in these cells.

Animals↗

Flower and fruit development in Arabidopsis thaliana.

The study of flower development has experienced great advances over the last 15 years. The most important landmark was the proposal of the ABC model in which three different functions of overlapping activities account for the development of the four rings of organs of the eudicot flower. Most interestingly, during recent years this simple and elegant model has been broadly accepted and is applicable to a wide range of plant species. However, recent advances in the characterization of protein interactions and the discovery of the SEPALLATA genes that are required for proper floral organ development have led to a revision of the ABC model. The largely accepted floral quartet model, which includes the new SEPALLATA function, postulates that the development of a specific floral organ is achieved by the formation of a single complex of different MADS-box proteins. The ultimate fate of the flower is to become a fruit, ensuring dispersal of the seeds and therefore survival of the species. The Arabidopsis fruit is a silique or pod. Only in the last five years important advances have been made in establishing the differentiation of the tissues required for the opening of the fruit: the valve margins and dehiscence zone. Classical genetic analyses and molecular biology approaches have pointed to the involvement of the transcription factors SHP, ALC and IND in the formation of these tissues and of FUL and RPL in repressing this identity in the bordering tissues, valves and replum, respectively.

Arabidopsis↗

Elevation of plasma high density lipoprotein-cholesterol in spontaneously diabetic Chinese hamsters.

The aim of this study is to define the change of plasma high density lipoprotein-cholesterol (HDL-C) in the spontaneously diabetic Chinese hamsters in the Asahikawa colony (CHA). These animals were divided into two groups according to fasting plasma glucose level; non-diabetic group and diabetic group. Plasma HDL-C was measured by a microliters-scale ultracentrifugal method using an RPL-42T rotor (Hitachi Koki Co.). The diabetic hamsters had hypoinsulinemia and hyperlipidemia. Plasma HDL-C in the diabetic group was significantly elevated as compared with the non-diabetic group. A significant positive correlation was observed in both groups between plasma HDL-C and total cholesterol. The male hamsters tended to have higher plasma HDL-C and total cholesterol levels than the female hamsters in either group. Moreover, an electrophoretic analysis showed that there was some relative increase in plasma very low density lipoprotein, low density lipoprotein and high density lipoprotein (HDL) in the diabetic hamsters. An ultracentrifugal analysis showed that plasma chylomicron appeared only in the diabetic hamsters. The heterogeneity of particle size of HDL was found by gradient gel electrophoresis. The apparent average molecular weight of HDL was approximately 265,000 in either group. It is concluded that plasma HDL-C increased with the advance of hyperglycemia and hyperlipidemia in insulin-deficient diabetic hamsters and that there was sex difference in the hamsters for plasma HDL-C and total cholesterol.

Animals↗

Vasoactive intestinal polypeptide (VIP) selectively stimulates prolactin release in healthy women.

The neuropeptide, vasoactive intestinal polypeptide (VIP), is released from the hypothalamus to the portal circulation, and experiments on animals provide evidence that it might modulate hormone secretion from the pituitary. Here we report the effects of VIP on the release of different pituitary hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyrotropin-releasing hormone (TSH), in normal women. Seven healthy women (aged 27-32; body weight 53-60 kg), with normal menses and receiving no medication, were tested on days 20-23 of their cycle. Porcine VIP was injected i.v. as a bolus dose of 1 mcg/kg body weight. Blood samples were collected 10 minutes prior to VIP administration and 5, 15, 30, 45, 60 and 90 minutes after VIP injection. Blood pressure and heart rate were continuously monitored. Hormone levels were determined by RIA. Stress, which can stimulate PRL release, was assayed by measuring the effect of placebo on hormone release (5 controls). VIP injection induced a significant (p less than 0.01) increase in plasma PRL levels. Basal PRL was 20.25 +/- 9.14 ng/ml; 5 minutes after VIP injection PRL levels rose to 45.0 +/- 14.9 ng/ml (p less than 0.01). At 15 minutes a plateau was reached (46.0 +/- 14.5 ng/ml), then the levels slowly decreased. VIP administration did not modify the plasma concentration of LH, FSH or TSH at any time during the observation period. The present study indicates that VIP might play a physiological role as a RPL-releasing factor in human beings.

Adult↗

Lactogenic hormones of the placenta and pituitary inhibit suckling-induced prolactin (PRL) release but not the ante-partum PRL surge.

Prolactin (PRL) and other lactogenic hormones feed back at the hypothalamus to inhibit PRL release. At midpregnancy, high circulating levels of placental lactogens (PL) terminate the mating-induced biphasic PRL surges in female rats. In the dark period preceding parturition, however, an ante-partum PRL surge occurs despite continuously high levels of PL. This study examined whether the lactogenic hormone negative feedback loop is altered during the ante-partum surge using two models: (i) pregnant rats given a hypothalamic implant of albumin, ovine PRL, or recombinant rat PL-I on Day 19 or 20 of pregnancy; and (ii) pregnant rats bearing a transplant of a rat choriocarcinoma cell line, Rcho-1 (PL-secreting), or HRP-1 (non-PL-secreting). Serial blood samples were taken via carotid cannula from all rats. Although lactogenic hormones placed in the hypothalamus reduced suckling-induced PRL release by 89%, hypothalamic implants of oPRL or recombinant rPL-I did not attenuate the ante-partum PRL surge. Rcho-transplanted rats also did not have a significantly reduced ante-partum PRL surge (peak PRL level, 131 ng/ml) compared with HRP-bearing rats (peak PRL level, 107 ng/ml). Northern blot analysis revealed that the Rcho-1 tumors expressed both PL-I and PL-II, while the HRP-1 tumors did not express either PL. The inability of the Rcho-1 transplants to inhibit the ante-partum PRL surge suggests that lactogenic hormone negative feedback is disrupted during the ante-partum period, possibly by the changing steroid profile associated with parturition.

Animals↗

Prevalence and clinical correlation of anti-phospholipid-binding protein antibodies in anticardiolipin-negative patients with systemic lupus erythematosus and women with unexplained recurrent miscarriages.

CONTEXT: Anti-phospholipid antibodies (aPL) are a heterogeneous group of autoantibodies, the presence of which is associated with thrombotic events and miscarriage. OBJECTIVE: To establish whether antibodies directed against phospholipid-binding plasma proteins such as beta(2)-glycoprotein I (beta(2)GPI), prothrombin (PT), and annexin V (Anx V) constitute a risk factor for thromboembolism in patients with systemic lupus erythematosus (SLE) and for miscarriage in women with recurrent pregnancy loss (RPL), independently of the presence of the classic anticardiolipin (aCL) antibodies, and whether their determination together with that of aCL would help to increase the diagnostic sensitivity of aPL tests. DESIGN: The prevalence of various antibodies directed toward phospholipids (CL and other anionic phospholipids [APL]) and phospholipid-binding proteins (beta(2)GPI, PT, and Anx V) was determined by immunoenzymatic methods in 311 serum samples. PATIENTS: Twenty-five patients with aCL-positive primary anti-phospholipid syndrome (pAPS); 89 patients with SLE, 23 of whom had thrombotic complications (SLE/APS) and 66 of whom had no thrombosis; and 77 women with unexplained recurrent pregnancy loss comprised our study group. One hundred twenty healthy subjects matched for age and sex were studied as the control group. RESULTS: Immunoglobulin (Ig) G and/or IgM aAPL, anti-beta(2)GPI, anti-PT, and IgG anti-Anx V antibodies were detected in 25 (100%), 20 (80%), 15 (60%), and 6 (24%), respectively, of the 25 aCL-positive pAPS patients; IgG and/or IgM aCL, aAPL, anti-beta(2)GPI, anti-PT, and IgG anti-Anx V antibodies were detected in 33 (37%), 42 (47%), 31 (35%), 40 (45%), and 12 (13%) of the 89 SLE patients, respectively. Of the 56 SLE patients who proved to be aCL negative, anti-beta(2)GPI was present in 3 patients (5%), anti-PT in 13 (23%) patients, and anti-Anx V in 5 (9%) patients. In the subset of 23 SLE/APS patients, IgG anti-PT prevalence was higher than that of the other autoantibodies (87% vs 70% aCL, 66% aAPL, 57% anti-beta(2)GPI, and 4% anti-Anx V), and in 26% of cases, IgG anti-PT was the only antibody present. Anti-PT had a slightly lower specificity than aCL (46% vs 49%); however, the occurrence of both antibodies brought the specificity to 92.4%. The highest risk for thrombosis in SLE patients was associated with the presence of IgG anti-PT antibody (odds ratio [OR] 15.3, P < .001, vs 6.5 aCL, 3.5 aAPL, 3.4 anti-beta(2)GPI, 0.2 anti-Anx V). Fifty-one of the 77 women with recurrent pregnancy loss were negative for all antibodies investigated; the prevalence of IgG and/or IgM aCL, aAPL, anti-beta(2)GPI, anti-PT, and IgG anti-Anx V antibodies was 6% (5), 12% (9), 6% (5), 16% (12), and 17% (13), respectively. Of the 67 aCL-negative women, none had anti-beta(2)GPI antibodies, 7 (11%) were anti-PT positive, and 13 (19%) were anti-Anx V positive. In the subgroup of 26 recurrent pregnancy loss patients who had at least one antibody, anti-Anx V was present in 50% of cases (in 42% as the sole antibody) and was the only antibody significantly associated with miscarriage (P = .02). CONCLUSIONS: The results of this study indicate that it is useful to measure anti-PT antibodies in addition to the more widely used aCL and anti-beta(2)GPI antibodies in the prognostic evaluation of SLE patients for the risk of thrombosis, and the results also confirm that anti-Anx V antibodies may play an important role in recurrent pregnancy loss.

Abortion, Spontaneous↗

[Measurements of Gamma-Knife helmet output factors using a radiophotoluminescent glass rod dosimeter and a diode detector].

A radiophotoluminescent (RPL) glass rod dosimeter (GRD) and a small active volume p-type silicon diode detector (stereotactic field detector, SFD) were used for the measurement of Gamma-Knife output factors. All measurements were done using a 16 cm diameter spherical polystyrene phantom with the detector at the focal spot of Gamma-Knife. The GRD system consists of small rod-shaped glass chip detectors and an automatic readout device. The output factors measured with GRD of the 14, 8 and 4 mm helmets relative to the 18 mm helmet are 0.981, 0.942 and 0.877, respectively. Similarly, the corresponding output factors measured with SFD are 0.980, 0.949 and 0.867, respectively. These output factors are comparable with the values given in a recent publication and the values recommended by Elekta, the manufacture. The angular dependence of these detectors is also measured using a linear accelerator-based stereotactic radiosurgery system. For the Gamma-Knife angle ranging from 6 to 36 degrees from the vertical axis, the measured angular dependence of the GRD is approximately 1.0% at a 4 MV x-ray beam. The response of SFD indicates approximately 3-4% directional dependence for the same angle range for a 6 MV x-ray beam. The Gamma-Knife helmet output factors measured with SFD are corrected for angular dependence. In summary, GRD can be a good candidate in measuring small field output factor. Due to an angular dependence the small p-type diode detector needs care when calculating the Gamma-Knife dose.

Glass↗

Reproductive outcome following hysteroscopic lysis of intrauterine adhesions: a result of 65 cases at Ramathibodi Hospital.

We reported the reproductive outcome of 65 patients with varying degrees of IUAs who underwent hysteroscopic adhesiolysis between August 1994 and December 1996 at Ramathibodi Hospital. Of the 65 patients treated, 29 had mild adhesions, 26 had moderate adhesions, and 10 had severe adhesions. Adhesions were lysed with hysteroscopic scissors in 25, with biopsy forceps through hysteroscope in 10, with electrosurgery using a monopolar probe in 22 patients, and with resectoscope in 8 patients. The mean duration of the procedure was 15 +/- 2.1 minutes. The mean follow-up was 12 +/- 1.4 months. Of the 44 patients who originally presented with secondary amenorrhea, 40 (90.9%) have normal menses, 4 (9.1%) have hypomenorrhea. Of the 6 patients who had hypomenorrhea, 5 (83.3%) have normal menses. Cyclic abdominal pain disappeared after treatment in all patients. Of the 45 patients with IUAs and infertility, 16 (35.6%) conceived. Two (20%) of the infertile patients with initially severe adhesions conceived. Of the 5 patients with RPL treated, delivered a full term baby and the other delivered a premature baby at 29 weeks of gestation. All 18 patients who delivered, had live births. Adhesion reformation was absent in patients with initially mild and moderate adhesion but occurred in 2 out of 10 (20%) patients with severe adhesions. These two patients initially suffered from secondary amenorrhea but reported hypomenorrhea after surgery. Both of them had tuberculosis of the genital tract. There were no serious complications occurring in all 65 procedures. All 65 patients were discharged a few hours after the operation.

Adolescent↗

Using capillary electrophoresis to study methylation effect on RNA-peptide interaction.

Methylation of RNA and proteins is one of a broad spectrum of post-transcriptional/translational mechanisms of gene expression regulation. Its functional signification is only beginning to be understood. A sensitive capillary electrophoresis mobility shift assay (CEMSA) for qualitative study of the methylation effect on biomolecules interaction is presented. Two RNA-peptide systems were chosen for the study. The first one consists of a 17-nucleotide analogue (+27-+43) of the yeast tRNA(Phe) anticodon stem and loop domain (ASL(Phe)) containing three of the five naturally occurring modifications (2'-O-methylcytidine (Cm(32)), 2'-O-methylguanine (Gm(34)) and 5-methylcytidine (m(5)C(40))) (ASL(Phe)-Cm(32),Gm(34),m(5)C(40)) and a 15-amino-acid peptide (named t(F)2: Ser(1)-Ile-Ser-Pro-Trp(5)-Gly-Phe-Ser-Gly-Leu(10)-Leu- Arg-Trp-Ser-Tyr(15)) selected from a random phage display library (RPL). A peptide-concentration-dependent formation of an RNA-peptide complex was clearly observable by CEMSA. In the presence of the peptide the capillary electrophoresis (CE) peak for triply methylated ASL(Phe) shifted from 18.16 to 20.90 min. Formation of the complex was not observed when an unmethylated version of ASL(Phe) was used. The second system studied consisted of the (+18)-(+44) fragment of the trans-activation response element of human immunodeficiency virus type 1 (TAR RNA HIV-1) and a 9-amino-acid peptide of the trans-activator of transcription protein (Tat HIV-1) Tat(49-57)-NH(2) (named Tat1: Arg(49)-Lys-Lys-Arg(52)-Arg-Gln-Arg-Arg- Arg(57)-NH(2)). In the presence of Tat(49-57)-NH(2) a significant shift of migration time of TAR from 18.66 min to 20.12 min was observed. Methylation of a residue Arg(52)-->Arg(Me)(2), crucial for TAR binding, strongly disrupted formation of the complex. Only at a high micromolar peptide concentration a poorly shaped, broad peak of the complex was observed. CE was found to be an efficient and sensitive method for the analysis of methylation effects on interaction of biomolecules.

Amino Acid Sequence↗

[A comparison of the helmet output factors for five Gamma-Knife units.].

A radiophotoluminescent (RPL) glass rod dosimeter (GRD) and a small active volume p-type silicon diode detector are used for the measurement of the helmet output factors from five Gamma-Knife units, which include four Model B units and a Model C unit. The output factors for the five units measured with the GRD from 14, 8 and 4 mm helmets relative to the 18 mm helmet are 0.984 +/- 0.003, 0.951 +/- 0.003 and 0.884 +/- 0.006, respectively. Similarly, the corresponding output factors measured with the p-type silicon diode detector are 0.983 +/- 0.002, 0.952 +/- 0.003 and 0.867 +/- 0.015, respectively. The output factors are corrected with the end effect for each helmet of the five units. The end effect time for the four Model B units ranges from 4 sec for the 18 mm helmet to 2 sec for the 4 mm helmet. The results for the Model C unit are within 1 sec for all the helmets. The output factors for the five units obtained from both detectors are in good agreement with the values in a recent publication and the values recommended by Elekta, the device manufacturer, except for that of the 4 mm helmet measured with the GRD. The average GRD output factor for the 4 mm helmet is 1.6% higher than Elekta's value, 0.870, but is in good agreement with the published value which was measured using small active volume detectors. The helmet output factors for the five Gamma-Knife units measured with the GRD agree within measurement deviation.

Glass↗

Developmental modulation of neuronal cell surface determinants.

Proceeding from the hypothesis that cellular differentiation processes are correlated with structural changes of the cell membrane, the expression of antigen and lectin receptors, as well as lectin-like molecules during migration and differentiation of pre- and perinatal neurons in the cerebral cortex, was analysed. It could be shown that a number of cell surface structures exist throughout the whole pre- and perinatal period, e.g. receptors for Robinia pseudoacacia lectin (RPL), pokeweed lectin (PWL) and concanavalin A (ConA) and the Ia and H-2-D/K antigens of the major histocompatibility complex (MHC). The expression of other cell surface structures, for example receptors for peanut and Limulus polyphemus lectin (LPL) and of Thy-1, is determined by the developmental stage; i.e. in the perinatal period higher amounts are found than in early prenatal stages. Binding sites for Phaseolus vulgaris lectin, PWL and anti-Thy-1.2 are not only demonstrated on perikaryal membranes, but additionally on diverse tangential or radial fibre structures. While on cells of the ventricular layer - the proliferating cell compartment - peanut lectin (PNL) receptors are observed in low density, LPL receptors in high density, in the migration zone, i.e. the intermediate layer, receptors are found predominantly for PNL and only few cells carry a significant number of LPL-binding sites. After the preneurons have migrated through the intermediate layer and the neighbouring cortical plate, remaining at the pia-near border of the latter, LPL receptors are again expressed on the cell surface of the now bipolar preneurons, while PNL receptors cannot be demonstrated any more. Experimental evidence is put forward indicating the possibility that this modulation of exposed carbohydrate residues on the cell surface might be mediated by a membrane-associated enzyme system on the same single molecule. For the investigation of neuronal cell interaction the ability of disintegrated suspended preneurons was used to reaggregate spontaneously in vitro and to build histiotypic cell formations within these reaggregates. It was found that this reaggregation of suspended neuronal single cells is dependent on the presence of ionized calcium, on the temperature, and on the conditions that influence the frequency of cell contacts. Furthermore, the structures expressed on the cell surface of preneurons during the pre- and perinatal period were investigated in regard to their influence on the reaggregation of these cells by means of a blockade by monoclonal antibodies or saccharides, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Atypical cells in the peripheral blood of chickens exposed to Marek's disease agent.

Atypical cells, containing opaque blue cytoplasmic globules when stained with Wright's or May-Grünwald-Giemsa stain, were observed in Gamefowl (GF-WSU) experimentally exposed by contact to a classical Marek's disease (MD) agent, and in White Leghorn chickens (RPL Line 7) in which group "spontaneous" cases of classical MD developed. Such cells were absent in uninfected control birds. The cells were most readily demonstrated in stained films of white blood cells of the peripheral blood after 24-hour culture in vitro. The atypical cells were present in the peripheral blood of chickens exposed to MD, but in numbers so few that the cells were rarely detected in direct blood smears.

Animals↗

Demonstration of a tumor-associated surface antigen in Marek's disease.

Surface antigenic markers were detected on three classes of Marek's disease (MD) tumor cells, i.e., MD lymphoma cells, cultured cells of the MSB-1 lymphoblastoid cell line, and JMV lymphoblastic leukemia cells, by indirect membrane immunofluorescent staining with serum from chickens immunized with JMV cells or from rabbits immunized with MSB-1 cells. This surface antigen was not detected on normal chicken lymphocytes, RPL-16 tumor cells (tranedormed by an avian RNA virus, or MD virus-infected fibroblasts that were positive for viral membrane antigen (MA). Furthermore, the surface antigen appeared unrelated to embryonic or histocompatibility antigens. This antigen is provisionally designated as a Marek's disease tumor-associated surface antigen (MATSA). The MATSA's on JMV, MSB-1 and MD lymphoma cells were related but not identical as demonstrated by antiserum titration, absorption and blocking tests with homologous and heterologous systems.

Analysis of Variance↗

Renal tubular tumors and atypical hyperplasias in B6C3F1 mice exposed to lead acetate during gestation and lactation occur with minimal chronic nephropathy.

Lead is a high-priority hazardous substance in humans and a renal carcinogen in adult rodents. This study assessed the carcinogenic potential and toxicity of gestational and lactational lead exposure in (C57BL/6NCr x C3H/HeN)F1 (hereafter called B6C3F1) mice. Effects of a renal tumor promoter [barbital sodium (BB)] on lead-initiated lesions were also studied. Pregnant female C57BL/6NCr mice (10-15/group) previously bred with C3H/HeN males were given lead acetate (0, 500, 750 and 1000 ppm lead) ad libitum in their drinking water, starting on gestation day 12 and continuing to 4 weeks postpartum. Offspring were then weaned and divided into same-sex groups of 23-25 and observed for a maximum of 112 weeks. Other groups received lead and then continuous BB (500 ppm) ad libitum in their drinking water from weaning onward. In control male offspring (0 lead/0 BB), renal proliferative lesions [(RPLs); defined as atypical tubular hyperplasia or tumor] occurred rarely (1 lesion-bearing mouse/23 mice examined, 4%) and did not include tumors. RPLs increased in a dose-related fashion with lead exposure (500 lead/0 BB, 4/25, 16%; 750 lead/0 BB, 6/25, 24%; 1000 lead/0 BB, 12/25, 48%) in male offspring and were often multiple. All lead-treated groups had renal tumors, including carcinoma, but these were most common at the highest dose (1000 lead/0 BB, 5/25). Lead-induced renal tumors arose in the absence of the extensive chronic nephropathy and lead inclusion bodies typically seen with lead carcinogenesis in rodents exposed chronically as adults. Postnatal BB exposure had no effect on RPL incidence (e.g., 1000 lead/500 BB, 8/25, 32%). Lead-treated female offspring also developed RPLs, including adenoma and carcinoma, but at a much lower rate than males. Thus, short-term lead exposure during the gestational/lactational period has carcinogenic potential in the mouse kidney.

Animals↗

[Long-acting and repeatable dose bromocriptine in the prolonged treatment of prolactinoma].

BACKGROUND: The presentations of intravenous or depot bromocriptine (bromocriptine LA or long acting, Pariodel LA and bromocriptine LAR or long acting repeatable, Pariodel LAR) have improved the efficacy and the tolerance of oral bromocriptine. In contrast to bromocriptine LA, bromocriptine LAR may be repeatedly administered intramuscularly. METHODS: Five patients with macroprolactinoma and 4 with microprolactinoma were included in the study. A 50 mg bottle of bromocriptine LAR was administered intramuscularly every month, over a minimum period of 6 months. PRL was determined prior to the study, 1, 3, 7, 14, and 28 days following the initial dose of bromocriptine and thereafter with monthly periodicity. RESULTS: The PRL values decreased in those patients with macroprolactinomas following the administration of bromocriptine LAR; in 2 patients the monthly doses of bromocriptine LAR was increased to 100 mg since the month after the initial dose PRL remained greater than 200 ng/ml with serum RPL normalizing in most of the patients at 6 months of treatment. In two of the three patients who presented visual changes a clear improvement was observed and in all the cases a reduction in the size of the macroprolactinoma was found upon CAT control at 6 months. The PRL values also decreased in the patients with microprolactinomas following administration of bromocriptine LAR, although the response was not as homogeneous as in the patients with macroprolactinomas due to that at 6 months 2 patients continued to have slightly elevated serum PRL levels. The microadenoma persisted in the control CAT at 6 months except in one case. Local and general tolerance to bromocriptine LAR was very good. CONCLUSIONS: This study indicates good tolerance to bromocriptine LAR, being a therapeutic option in the treatment of macroprolactinomas.

Adult↗