Amendment of the OMERACT ultrasound definitions of joints' features in healthy children when using the DOPPLER technique.

BACKGROUND: Recently preliminary ultrasonography (US) definitions, in B mode, for normal components of pediatric joints have been developed by the OMERACT US group. The aim of the current study was to include Doppler findings in the evaluation and definition of normal joint features that can be visualized in healthy children at different age groups. METHODS: A multistep approach was used. Firstly, new additional definitions of joint components were proposed during an expert meeting. In the second step, these definitions, along with the preliminary B-mode-US definitions, were tested for feasibility in an exercise in healthy children at different age groups. In the last step, a larger panel of US experts were invited to join a web-based consensus process in order to approve the developed definitions using the Delphi methodology. A Likert scale of 1-5 was used to assess agreement. RESULTS: Physiological vascularity and fat pad tissue were identified and tested as two additional joint components in healthy children. Since physiological vascularity changes over the time in the growing skeleton, the final definition of Doppler findings comprised separate statements instead of a single full definition. A total of seven statements was developed and included in a written Delphi questionnaire to define and validate the new components. The final definitions for fat pad and physiological vascularity agreed by the group of experts reached 92.9% and 100% agreement respectively in a web survey. CONCLUSION: The inclusion of these two additional joints components which are linked to detection of Doppler signal in pediatric healthy joints will improve the identification of abnormalities in children with joint pathologies.

Exposure to increased levels of estradiol during development can have long-term effects on the response to undernutrition in female rats.

OBJECTIVES: Undernutrition during development alters the expression of peptides that control energy expenditure and feeding behavior. Estrogens can also modulate these peptides. Here, we analyze whether the early postnatal administration of estradiol modulates the effects of undernutrition on neuroendocrine parameters in adult female Wistar rats. METHODS: Control rats were fed a control diet. Undernourished pups were submitted to a restricted diet with half of the undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from postnatal day (P) 6 until P13. Quantitative real-time polymerase chain reaction was performed to determine expression in the hypothalamus of agouti-related peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript. Plasma estradiol, testosterone, and adiponectin levels were measured by enzyme-linked immunosorbent assay. Total and acylated ghrelin levels were measured in plasma by radioimmunoassay. Insulin and leptin were measured by mulitplex immunoassays. RESULTS: Undernourishment decreased body weight, fat mass, plasma leptin and insulin levels, and hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY mRNA levels, and in plasma adiponectin levels were found in undernourished animals. Early postnatal treatment with EB to undernourished female rats reversed the effects of undernutrition on adult hypothalamic POMC mRNA levels. In addition, neonatal EB treatment to undernourished females significantly decreased adult plasma testosterone, estradiol, and acylated ghrelin levels. DISCUSSION: Our results suggest that increased estradiol during a critical period of development has the capacity to modulate the alterations that undernutrition produces on energy metabolism.

EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice.

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.

Influence of sex and level on marathon pacing strategy. Insights from the New York City race.

Different pacing profiles have been identified in the literature for endurance sporting events: the 'positive', 'negative', 'even', 'parabolic shaped' and 'variable pacing'. Most studies have focused on competitive or elite athletes (including winners) without considering more recreational runners, for many of whom the primary goal is simply to finish the event. The major city marathons provide a large heterogeneous sample to compare the pacing profiles of competitive vs. recreational runners, and thus to understand pacing more broadly. A total of 190,228 New York finishers' (69,316 women) marathon times (from 2006 to 2011) were assessed. Although all runners developed a positive pace profile, a lower variability of speed through the race was found in the top runners (coefficient of variation (CV) for speed during 5-km splits: 7.8% (men) and 6.6% (women)) compared with the less successful runners (CV ranging from 8.3 to 14.4%). Both men and women try to maintain an even pace profile along the marathon course, partly by avoiding an excessively fast start that might result in a pronounced decrease in the speed in the second half of the race.

Androgen receptor deficiency alters the arginine-vasopressin sexually dimorphic system in Tfm rats.

In rodents as well as in many other mammalian and non-mammalian species, the arginine-vasopressin (AVP) system includes a parvocellular sexually dimorphic portion located within the bed nucleus of the stria terminalis (BST), the medial amygdaloid nucleus (MeA) and the lateral septum. In this system, males have more cells and denser projections than females, neurons show androgen and estrogen receptors, and gonadal hormones are required for the activation. However, the role of these hormones for the differentiation of the system is not clear. Previous studies performed on aromatase knockout mice suggested that estradiol is not necessary for the differentiation of the system, but it is important for its activation in adulthood. To elucidate the role of androgens on differentiation and functioning of AVP parvocellular system, we compared male and female rats with a non-functional mutation of androgen receptor (Tfm, testicular feminization mutation) to their control littermates. Our data show that the lack of a functional androgen receptor significantly decreases the expression of AVP immunoreactivity within the BST and MeA of male Tfm. Thus supporting the hypothesis that androgens, through the action of their receptor, should have a relevant role in the organization and modulation of the AVP parvocellular sexually dimorphic system.

Estrogenic regulation of NADPH-diaphorase in the supraoptic and paraventricular nuclei under acute osmotic stress.

Estrogen receptors (ERs) α and ß are involved in the regulation of the nitrergic system in the supraoptic (SON) and paraventricular (PVN) nuclei under basal conditions. In this study we have assessed whether ERs are also involved in the modulation of the nitrergic system in the SON and PVN under acute systemic hypertonic conditions. Adult ovariectomized rats received a single injection of either estradiol, a selective ERα agonist, a selective ERß agonist, a selective ERα antagonist, a selective ERß antagonist or vehicle. Twenty-four hours later, animals received one i.p. injection of 1.5M NaCl to induce osmotic stress and were sacrificed after two additional hours. The number of NADPH-diaphorase-positive cells in the SON and PVN was determined. Their number in the SON was not affected by NaCl administration, whereas in the four PVN subdivisions it was decreased after NaCl administration. Estradiol and the ERα agonist prevented the action of NaCl in the four subdivisions of the PVN. In contrast, the inhibition of ERα enhanced the effect of NaCl, inducing a further decrease in the number of NADPH-diaphorase-positive cells. Moreover, the ERß agonist enhanced and the ERß antagonist blocked the effect of NaCl on the number of NADPH-diaphorase-positive neurons in the SON and in the medial magnocellular subdivision of the PVN. These findings indicate that estradiol regulates the nitrergic system in the SON and PVN under acute osmotic stress conditions, but the effects specifically depend on the anatomical subregions and different ERs.

Role of oestrogen receptors on the modulation of NADPH-diaphorase-positive cell number in supraoptic and paraventricular nuclei of ovariectomised female rats.

Modulation of the nitric oxide producing system (demonstrated via the NADPH-diaphorase histochemical reaction) by oestradiol has been established in several structures of the rat brain. The present study aimed to explore the possible regulation of NADPH-diaphorase activity by oestradiol in neurones of the supraoptic (SON) and paraventricular (PVN) nuclei and the role of oestrogen receptors (ERα and ERß) in this regulation. Adult ovariectomised rats were divided into six groups and injected either with vehicle or a single dose of oestradiol, a selective ERα agonist-PPT [4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol], a selective ERß agonist-DPN [2,3-bis(4-hydroxyphenyl)-propionitrile], a selective ERα antagonist-MPP [1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride] or a selective ERß antagonist-PHTPP (4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol). The number of NADPH-diaphorase positive elements in the SON and the PVN was modulated by both ERs but, depending on the nucleus, ERα and ERß ligands induced different effects. These results suggest that the regulation of nitrergic system by ERs may play a role in the control of oestrogen-dependent physiological mechanisms regulated by the SON and the PVN.

Effects of undernourishment on the hypothalamic orexinergic system.

The present study examined the effects of a severely restricted diet during the pre- and postnatal periods with later nutritional rehabilitation on orexin hypothalamic neurons in male and female Wistar rats. Immunocytochemistry was used to reveal orexin-immunoreactive (orexin-ir) cells in the ventromedial hypothalamus (VMH), dorsomedial hypothalamus (DMH), lateral hypothalamic area (LH) and the perifornical nucleus (PF). Dietary restriction decreased the number of orexin-ir cells in the LH, whereas DMH or PF orexin-ir populations were not affected in either male or female rats. Nutritional rehabilitation resulted in a differential recovery that depended on the period during which rehabilitation occurred and on the sex of the animal. In summary, our study suggests that the hypothalamic nuclei implicated in eating behavior present a differential vulnerability to adverse environmental conditions during development. Specifically, among the studied nuclei only the LH orexin-ir cells were sensitive to severe food deprivation during development in male and female rats. These results suggest that starvation interferes with developmental events that occur during CNS sexual differentiation.

Androgen receptors are required for full masculinization of nitric oxide synthase system in rat limbic-hypothalamic region.

The neuronal nitric oxide synthase (nNOS) is involved in the control of male and female sexual behavior and its distribution in several regions of the limbic-hypothalamic system, as well as its coexistence with gonadal hormones' receptors, suggests that these hormones may play a significant role in controlling its expression. However, data illustrating the role of gonadal hormones in controlling the nNOS expression are, at present, contradictory, even if they strongly suggest an involvement of testosterone (T) in the regulation of nNOS. The action of T may be mediated through androgen (AR) or, after aromatization to estradiol (E(2)), through estrogen receptors. To elucidate the role of AR on nNOS expression, we compared male and female rats with a non-functional mutation of AR (Tfm, testicular feminization mutation) to their control littermates. We investigated some hypothalamic and limbic nuclei involved in the control of sexual behavior [medial preoptic area (MPA), paraventricular (PVN), arcuate (ARC), ventromedial (VMH) and stria terminalis (BST) nuclei]. In BST (posterior subdivision), VMH (ventral subdivision), and MPA we detected a significant sexual dimorphism in control animals and a decrease of nNOS positive elements in Tfm males compared to their littermate. In addition, we observed a significant increase of nNOS positive elements in BST (posterior) of Tfm females. No significant changes were observed in the other nuclei. These data indicate that, contrary to current opinions, androgens, through the action of AR may have a relevant role in the organization and modulation of the nNOS hypothalamic system.

Recommendations for the content and conduct of European League Against Rheumatism (EULAR) musculoskeletal ultrasound courses.

OBJECTIVE: To develop education guidelines for the conduct of future European League Against Rheumatism (EULAR) musculoskeletal ultrasound (MSUS) courses. METHODS: We undertook a consensus-based, iterative process using two consecutive questionnaires sent to 29 senior ultrasonographer rheumatologists who comprised the faculty of the 14th EULAR ultrasound course (June 2007). The first questionnaire encompassed the following issues: type of MSUS educational model; course timing; course curriculum; course duration; number of participants per teacher in practical sessions; time spent on hands-on sessions; and the requirements and/or restrictions for attendance at the courses. The second questionnaire consisted of questions related to areas where consensus had not been achieved in the first questionnaire, and to the topics and pathologies to be assigned to different educational levels. RESULTS: The response rate was 82.7% from the first questionnaire and 87.5% from the second questionnaire. The respondents were from 11 European countries. The group consensus on guidelines and curriculum was for a three-level education model (basic, intermediate and advanced) with timing and location related to the annual EULAR Congresses. The topics and pathologies to be included in each course were agreed. The course duration will be 20 h. There will be a maximum of six participants per teacher and 50-60% of total time will be spent on practical sessions. There was also agreement on prerequisite experience before attending the intermediate and advanced courses. CONCLUSION: We have developed European agreed guidelines for the content and conduct of EULAR ultrasound courses, which may also be recommended to national and local MSUS training programmes.

Assessment of the joint recesses and tendon sheaths in healthy children by high-resolution B-mode and power Doppler sonography.

OBJECTIVE: To describe or determine reference values for the intracapsular cavity and its joint recess of the hip, knee and joints of the hand and for the tendon sheaths of fingers, examined with B-mode gray-scale ultrasonography (US) and power Doppler (PD) in healthy children. METHODS: Sixty healthy children (31 boys and 29 girls; age range 2-16 years) were examined bilaterally with gray-scale and PD US (after obtaining the informed consent), using a standardized technique. The maximum distance from bone surface to the outer margin of the capsule (namely, intracapsular cavity) and its joint recess of hip, knee, wrist, non-thumb metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hand were measured with US. Mean values +/- 2 SD (standard deviation) were indicated as reference values. RESULTS: None of the children showed joint hip fluid. In 5% of the children younger than 5 years an intra-capsular PD flow signal was detected in the posterior layer of the hip capsule. Fluid was detected in 60 % of the suprapatellar recesses. A small amount of fluid was detected within synovial recesses of the fingers, most commonly in the 2 MCP and PIP joints. Less frequently, a hypoechoic rim was detected around the finger flexor tendons on the palmar surface of the metacarpal bone. CONCLUSION: High-resolution US evidences a normal small amount of fluid located at the MCP and IFP joint recesses and/or the flexor tendon sheaths without any PD flow signal in healthy children, that is relevant for interpreting ultrasonographic findings in children with inflammatory diseases.

[Maximum stability of thermolabile drugs outside the refrigerator]. / Estabilidad máxima de los medicamentos termolábiles fuera de nevera.

OBJECTIVE: To review the maximum stability of thermolabile drugs at room temperature (22-25 degrees C) in order to quickly act in case of breakage of the cold chain. METHOD: The study included all drugs available in the pharmacy service from August 17, 2004 to October 15 of the same year, date in which the review was performed, that had to be kept at a temperature ranging between 2 degrees and 8 degrees C. Different drug laboratories were contacted and asked for written information on the matter. RESULTS: The results are reported in a table. One hundred seventy three medicinal products including 83 drugs were reviewed. CONCLUSIONS: Some information provided by the pharmaceutical industry allows the use of drugs even when the cold chain has been broken. This information must be used only in isolated cases, not as a routine.

Estabilidad máxima de los medicamentos termolábiles fuera de nevera / Maximum stability of thermolabile drugs outside the refrigerator

Objetivo: Revisar la estabilidad máxima de los medicamentostermolábiles a temperatura ambiente (22-25 °C) con el fin depoder actuar rápidamente en caso de ruptura de la cadena de frío.Método: Se incluyeron en el estudio todos aquellos principiosactivos disponibles en el servicio de farmacia desde el 17 de agostodel 2004 hasta el 15 de octubre del mismo año, fecha en laque se llevó a cabo la revisión, y que requerían para su conservaciónuna temperatura entre 2 y 8 °C. Se contactó con los diferenteslaboratorios farmacéuticos solicitándoles información porescrito al respecto.Resultados: Se muestran en forma de tabla. Se revisaron173 especialidades farmacéuticas correspondientes a 83 principiosactivos.Conclusiones: Existe información proveniente de la industriafarmacéutica que permite la utilización de medicamentos para losque se ha roto la cadena de frío. Esta información ha de ser únicamenteempleada en casos puntuales, y no de manera rutinaria

Objective: To review the maximum stability of thermolabiledrugs at room temperature (22-25 °C) in order to quickly act incase of breakage of the cold chain.Method: The study included all drugs available in the pharmacyservice from August 17, 2004 to October 15 of the sameyear, date in which the review was performed, that had to be keptat a temperature ranging between 2° and 8 °C. Different druglaboratories were contacted and asked for written information onthe matter.Results: The results are reported in a table. One hundredseventy three medicinal products including 83 drugs were reviewed.Conclusions: Some information provided by the pharmaceuticalindustry allows the use of drugs even when the cold chain hasbeen broken. This information must be used only in isolatedcases, not as a routine

Effects of gonadal hormones on central nitric oxide producing systems.

Nitric oxide-containing neurons are widely distributed within the CNS, including regions involved in the control of reproduction and sexual behavior. The expression of neuronal nitric oxide synthase is influenced by testosterone in male rat, and by estrogens in female. Moreover, nitric oxide synthase may co-localize with gonadal hormones' receptors. Gonadal hormones may influence nitric oxide synthase expression in adulthood as well as during the development. In fact, in mice knockout for estrogen receptor alpha, the nitric oxide synthase-expressing population is deeply reduced in specific regions. In physiological conditions, the female in mammalian species is exposed to short-term changes of gonadal hormones levels (estrous cycle). Our recent studies, performed in the rat vomeronasal system and in mouse hypothalamic and limbic systems reveal that, in rodents, the expression of nitric oxide synthase-producing elements within regions relevant for the control of sexual behavior is under the control of gonadal hormones. The expression of nitric oxide synthase may vary according to the rapid variations of hormonal levels that take place during the estrous cycle. This seems in accordance with the hypothesis that gonadal hormone activation of nitric oxide-cyclic guanosine-monophosphate pathway is important for lordosis behavior, as well as that this system is activated during mating behavior. Finally, comparative data available for other vertebrates suggest that class-specific and species-specific differences occur in the nitric oxide synthase system of hypothalamus and limbic structures. Therefore, particular caution is needed to generalize data obtained from studies in rodents.

Ultrasonographic findings in knee osteoarthritis: a comparative study with clinical and radiographic assessment.

OBJECTIVE: To compare ultrasonographic (US) findings with clinical and radiographic assessment in knee osteoarthritis (OA). METHODS: Fifty patients with primary knee OA were studied. Clinical assessment of both knees was performed by the same rheumatologist who recorded a visual analogue scale (VAS) for pain (VASP). All patients underwent a US examination of their knees by a second blinded rheumatologist. Weight-bearing anteroposterior and lateral knee radiographs were read by a third blinded rheumatologist who assessed the Kellgren and Lawrence (K-L) grade, the femorotibial (FT) space width and the presence of patello-femoral degenerative signs. RESULTS: Forty patients had bilateral symptomatic knee OA and 10 unilateral symptomatic OA. All knees showed radiographic FT degenerative signs. US findings in symptomatic knees were effusion (47%), protrusion of the medial meniscus (MMP) with displacement of the medial collateral ligament (MCLD) (61%) and Baker's cyst (22%). US effusion, MMP and MCLD were associated with a significantly higher VAS score for pain (P<0.05). MMP was associated with medial FT space width (P<0.05). Patients who had a difference between VAS score for pain in each knee greater than 30 (28 patients) showed significantly more unilateral effusion, MMP, MCLD and worse K-L grade in the more symptomatic knee than those with a difference lesser than 30 (22 patients). CONCLUSION: Knee effusion and MMP with MCLD are associated with pain in knee OA. In addition, MMP may contribute to the radiographic medial FT space narrowing. We propose US for assessing periarticular and intraarticular abnormalities involved in the pathophysiology of knee OA.

The development of sex differences in the locus coeruleus of the rat.

Development of sex differences in the locus coeruleus (LC) is investigated. The LC is a sexually dimorphic structure in which the female manifests a larger volume and greater number of neurons than do males. Male and female Wistar rats were sacrificed on prenatal days (E) 16 and 20 and postnatally (P) on days 1, 3, 7, 15, 35, 45, 60, and 90. Male and female rats show a continuous increase in the number of neurons after birth that stops in the males by P45 and in females by P60. These findings point out the existence of different patterns of development in male and female rats and may suggest that sex differences could be established because of the existence of a differential period of neurogenesis in both sexes in the postpubertal period.

Effects of melatonin on fuel utilization in exercised rats: role of nitric oxide and growth hormone.

We have previously reported that melatonin modifies carbohydrate and lipid utilization in exercised rats, maintaining glycemia and reducing plasma and liver lactate and plasma beta-hydroxybutyrate. This study was undertaken to determine whether effects on fuel metabolism were related to changes in nitric oxide (NO) production or growth hormone (GH) secretion. Male Wistar rats received melatonin i.p. at a dose of 0.5 mg/kg body weight 30 min before being exercised to exhaustion on a treadmill at a speed of 24 m/min and a 12% slope. Melatonin ameliorated the decrease in plasma glucose and the increase in plasma urea, free fatty acid, beta-hydroxybutyrate, and nitrite induced by exercise. Melatonin-treated exercised rats had significantly elevated liver glycogen content and hepatic tissue showed a lowered expression of both inducible and constitutive NO synthase (iNOS and cNOS). Administration of the NO inhibitor NG-nitro-L-arginine (L-NAME) to exercised rats caused a significant reduction in plasma nitrite, but liver glycogen and biochemical parameters in blood did not significantly differ from untreated exercised animals, indicating the absence of a direct association between melatonin effects on fuel metabolism and NO levels. Although results of treatment with pyridostigmine, a cholinergic agonist drug that stimulates GH release, partially differed from that of melatonin, modulation of GH secretion could play a role in the metabolic actions of the hormone because effects of melatonin on exercised rats were almost completely blocked by simultaneous administration of L-NAME.

Effect of epomediol on ethinyloestradiol-induced changes in bile acid and cholesterol metabolism in rats.

1. Epomediol is a terpenoid compound that has been reported to stimulate bile acid synthesis and to reverse 17alpha- ethinyloestradiol-induced cholestasis. The aim of the present study was to investigate the contribution of changes in bile acid and cholesterol metabolism to the protective effects of epomediol in ethinyloestradiol-treated rats. Animals received epomediol for 5 days at 100 mg/kg daily, i.p., ethinyloestradiol for 5 days at 5 mg/kg, s.c., or a combination of both drugs. 2. When compared with control animals, epomediol treatment resulted in a significant increase in bile flow (+42%) and in the secretion of bile acids (+74%) and cholesterol (+42%). Ethinyloestradiol administration caused a significant decrease in bile flow (-43%), bile acid secretion (-37%) and cholesterol secretion (-45%). Bile flow, bile acid secretion and cholesterol secretion were significantly increased in animals receiving ethinyloestradiol plus epomediol compared with ethinyloestradiol-treated rats (+13, +29 and +31%, respectively). 3. Both cholesterol 7alpha-hydroxylase and hydroxy-3- methylglutaryl coenzyme A reductase activities were significantly increased in epomediol-treated rats (+30 and +96%, respectively). Cholesterol 7alpha-hydroxylase activity was significantly reduced by ethinyloestradiol (-22%) and did not differ from control values in animals receiving epomediol plus ethinyloestradiol. Levels of cholesterol 7alpha-hydroxylase mRNA were elevated (+41%) by epomediol, but were not significantly modified by ethinyloestradiol or ethinyloestradiol plus epomediol. 4. It is concluded that epomediol enhances bile acid secretion by increasing the expression of cholesterol 7alpha-hydroxylase. Changes in bile acid metabolism contribute to the effects of epomediol in rats with ethinyloestradiol-induced cholestasis.

Postnatal cell proliferation and death in a lateralized, gender-related, asymmetric nucleus.

Sexual differentiation and lateralization of neurone number in a discrete forebrain nucleus (SDApc) related to masculine vocal emission, occur contemporaneously in postnatal (P0-P15) gerbils. Stereological estimates of cell proliferation and death during SDApc organization were made by BrdU labelling and pyknosis, respectively. Results confirmed that rates of apoptosis were greater in females and lateralized in males. Immunoreactive BrdU cells, located in the SDApc at P0-P6, with low levels at P15, were not numerically different between the sexes. Only at one age, P0, in males, was a left-right difference seen in BrdU-immunoreactive cell numbers. Microglia, identified by isolectin immunostaining, were numerically similar to BrdU cells. We suggest that apoptosis, rather than neurogenesis, differentiates and lateralizes SDApc organization, and proliferating cells are microglia, phagocytosing debris.