Seroepidemiology of varicella zoster virus infection in Vojvodina, Serbia.

The present cross-sectional serosurvey constitutes the first effort to describe the varicella zoster virus (VZV) seroepidemiology in Serbia. An age-stratified serum bank of 3570 residual samples collected between 2015 and 2016 in each of the seven districts of the Vojvodina Province was tested for IgG anti-VZV antibodies with an enzyme immunoassay. Results were standardised into common units according to the European Sero-Epidemiology Network (ESEN2) methodology. Univariable and multivariable analyses were used to examine the relationships between standardised anti-VZV positivity or logarithmically transformed antibody titres and demographic features of study subjects. Seropositivity (85% overall) increased with age, in parallel with geometric mean titres. By the time of school entry, 68% of children were immune. The slower subsequent acquisition of immunity leaves epidemiologically relevant proportions of adolescents (7%), young adults (6%) and especially females of reproductive age (6%) prone to more severe forms of varicella. In the ongoing pre-vaccine era, natural infection provides a high level of collective immunity, with the highest VZV transmission in children of preschool age. The detected gaps in VZV immunity of the Serbian population support the adoption of the official recommendations for varicella immunisation of non-immune adolescents and young adults, including non-pregnant women of childbearing age.

The use of an electronic clinical rule to discontinue chronically used benzodiazepines and related Z drugs.

PURPOSE: The chronic use of benzodiazepines and benzodiazepine-related drugs (BZ/Z) in older people is common and not without risks. The objective of this study was to evaluate whether the implementation of a clinical rule promotes the discontinuation of chronically used BZ/Z for insomnia. METHODS: A clinical rule, generating an alert in case of chronic BZ/Z use, was created and applied to the nursing home (NH) setting. The clinical rule was a one-off intervention, and alerts did not occur over time. Reports of the generated alerts were digitally sent to NH physicians with the advice to phase out and eventually stop the BZ/Z. In cases where the advice was adopted, a follow-up period of 4 months on the use of BZ/Z was taken into account in order to determine whether the clinical rule alert led to a successful discontinuation of BZ/Z. RESULTS: In all, 808 NH patients were screened. In 161 (19.1%) of the patients, BZ/Z use resulted in a clinical rule alert. From these, the advice to phase out and stop the BZ/Z was adopted for 27 patients (16.8%). Reasons for not following the advice consisted of an unsuccessful attempt in the past (38 patients), patients family and/or patient resistance (37 patients), the non-continuous use of BZ/Z (32 patients) and indication still present (27 patients). Of the 12 NH physicians, seven adopted the advice. CONCLUSIONS: The success rate of a clinical rule for discontinuation of chronically used BZ/Z for insomnia was low, as reported in the present study. Actions should be taken to help caregivers, patients and family members understand the importance of limiting BZ/Z use to achieve higher discontinuation rates.

Ongoing mumps outbreak in Novi Sad, the autonomous province of Vojvodina, Serbia, January to April 2012.

From 16 January to 30 April 2012, a total of 119 cases of mumps were notified in Novi Sad, Serbia. Of these cases, 89 (75%), were among students. The average age of cases was 22 years-old (range 3-37). The outbreak is still ongoing in Novi Sad and is spreading to other parts of the Vojvodina province. As of 30 April, 209 cases have been notified in the province among those 119 from Novi Sad.

Additional value of a triggerlist as selection criterion in identifying patients at high risk of medication-related hospital admission: a retrospective cohort study.

BACKGROUND: Of all hospital admissions in older patients, 10-30% seem to be medication-related. However, medication-related admissions are often unidentified in clinical practice. To increase the identification of medication-related hospital admissions in older patients a triggerlist is published in the Dutch guideline for polypharmacy. AIM: To assess whether the triggerlist has value as selection criterion to identify patients at high risk of medication-related hospital admissions. METHOD: This retrospective cohort study was carried out in 100 older (≥ 60 years) patients with polypharmacy and having two triggers from the triggerlist. The admissions were assessed as either possibly or unlikely medication-related according to the Assessment Tool for identifying Hospital Admissions Related to Medications. RESULTS: Of all the admissions 48% were classified as possibly medication-related. Patients with a possible medication-related hospital admission were more likely to have an impaired renal function (p = 0.015), but no differences with regard to age, sex, comorbidity or number of medicines were found. CONCLUSION: The high prevalence of medication-related hospital admissions, suggests the triggerlist may have added value as selection criterion in a cohort of older patients with polypharmacy and can be used to improve the identification of a population at high risk of medication-related hospital admissions.

Daidzein administration positively affects thyroid C cells and bone structure in orchidectomized middle-aged rats.

SUMMARY: Thyroid C cells hormone, calcitonine, inhibits bone resorption. We have demonstrated that daidzein treatment of orchidectomized rats (model for osteoporosis) stimulated C cells and increased trabecular bone mass. These results suggest that, besides direct action, daidzein may also affect bone structure indirectly through enhancement of thyroid C cell activity. INTRODUCTION: Thyroid C cells produce calcitonin (CT) which acts as an inhibitor of bone resorption. In this study, the influence of daidzein treatment on thyroid C cells, bone structure, and bone function in orchidectomized (Orx) middle-aged rats was investigated. METHODS: Sixteen-month-old Wistar rats were divided into Orx and sham-operated (SO) groups. Half the Orx rats were given subcutaneous injections of daidzein (30 mg/kg b.w./day) for 3 weeks. CT-immunopositive thyroid C cells were morphometrically analyzed. The metaphyseal region of the proximal tibia was measured histomorphometrically, and cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated. Serum samples were analyzed for CT and osteocalcin (OC), calcium (Ca) and phosphorus concentrations, and urine samples for Ca levels. RESULTS: Treatment of Orx animals with daidzein significantly increased volume of C cells compared to the Orx rats. Daidzein also enhanced B.Ar, Tb.Th, and Tb.N and reduced Tb.Sp. The serum OC and urinary Ca concentrations decreased significantly in comparison with the Orx group. CONCLUSIONS: These findings indicate that daidzein treatment stimulates thyroid C cells, increase trabecular bone mass, and decrease bone turnover in Orx middle-aged rats, which is the model of male osteoporosis.

Ongoing outbreak of aseptic meningitis associated with echovirus type 30 in the City of Novi Sad, Autonomous Province of Vojvodina, Serbia, June - July 2010.

Since June 2010, incidence of aseptic meningitis has increased in Novi Sad, Autonomous Province of Vojvodina, Serbia. From 2 June to 25 July 2010, 80 cases of aseptic meningitis were notified, with an incidence rate ranging from 10 to 366 per 100,000 population in different local communities. The majority of cases (n=64) were aged between two and 15 years. Echovirus 30 was cultured from two of four cerebrospinal fluid specimens. The outbreak, for which no common source has yet been identified, is ongoing.

Are somatosensory evoked potentials of the tibial nerve the most sensitive test in diagnosing multiple sclerosis?

BACKGROUND: Multiple sclerosis (MS) is mostly diagnosed clinically, but the diagnosis has significantly improved through the use of brain magnetic resonance imaging (MRI), testing of cerebrospinal fluid, and multimodal evoked potentials (MEPs). Even though MRI is the superior method in diagnosing this illness, MEPs remain important because they can detect clinically silent lesions in the sensory and motor pathways of the central nervous system (CNS). AIM: The aim of the study is to test the diagnostic sensitivity of MEPs and MRI and the ratio of their sensitivity in patients with MS. MATERIALS AND METHODS: The study subjects included 293 patients with MS with disease duration of two to six years: 249 patients with relapsing-remitting (RR) MS and 44 with primary-progressive (PP) MS. All patients were subjected to an MRI brain scan, visual evoked potentials (VEPs), median somatosensory evoked potentials (SEPs), tibial somatosensory evoked potentials (SEPs), and auditory evoked potentials (AEPs). Abnormal Findings Included : changed wave morphology, interside difference in wave amplitude, absolute and interwave latency increased by 2.5 SD as compared with the control group. The control group comprised of 35 healthy subjects. Results : In this study the most abnormal findings were tibial SEPs, median SEPs, and VEPs. Our results suggest different sensitivity of MEPs in patients suffering from different forms of MS. In RR-MS the sensitivity of tibial SEPs was statically significant (Fischer's exact probability test) as compared to other evoked potential modalities. Similarly VEPs were more sensitive as compared to AEPs. In the PP-MS, median SEPs have been found to be more sensitive than VEPs, while tibial SEPs have been found to be more sensitive than AEPs. There was no significant difference in the sensitivity of MRI and MEPs both the forms of MS. CONCLUSION: Tibial SEPs produce the most abnormal results and the highest sensitivity in the RR-MS. We propose that this test as useful criterion for the diagnosis of MS.

Medication-related hospital admissions and readmissions in older patients: an overview of literature.

Background The number of medication related hospital admissions and readmissions are increasing over the years due to the ageing population. Medication related hospital admissions and readmissions lead to decreased quality of life and high healthcare costs. Aim of the review To assess what is currently known about medication related hospital admissions, medication related hospital readmissions, their risk factors, and possible interventions which reduce medication related hospital readmissions. Method We searched PubMed for articles about the topic medication related hospital admissions and readmissions. Overall 54 studies were selected for the overview of literature. Results Between the different selected studies there was much heterogeneity in definitions for medication related admission and readmissions, in study population and the way studies were performed. Multiple risk factors are found in the studies for example: polypharmacy, comorbidities, therapy non adherence, cognitive impairment, depending living situation, high risk medications and higher age. Different interventions are studied to reduce the number of medication related readmission, some of these interventions may reduce the readmissions like the participation of a pharmacist, education programmes and transition-of-care interventions and the use of digital assistance in the form of Clinical Decision Support Systems. However the methods and the results of these interventions show heterogeneity in the different researches. Conclusion There is much heterogeneity in incidence and definitions for both medication related hospital admissions and readmissions. Some risk factors are known for medication related admissions and readmissions such as polypharmacy, older age and additional diseases. Known interventions that could possibly lead to a decrease in medication related hospital readmissions are spare being the involvement of a pharmacist, education programs and transition-care interventions the most mentioned ones although controversial results have been reported. More research is needed to gather more information on this topic.

The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.

We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.

Au dimers on thin MgO(001) films: flat and charged or upright and neutral?

A combination of low temperature scanning tunneling microscopy (STM) and theoretical calculations is used to investigate Au dimers, supported on thin MgO(001) films, whose thickness was chosen such that charge transfer from the Ag substrate to the deposited Au is possible. Au dimers exist not only in an upright geometry--as theoretically predicted to be the most stable configuration--but also as flat lying dimers which populate a manifold of different azimuthal orientations. Apart from the difference in adsorption configurations, these two isomers exhibit rather different electronic structures: while upright dimers are neutral, flat ones are charged.

Consummatory behavior and metabolic indicators after central ghrelin injections in rats.

Ghrelin, an endogenous ligand for the growth-hormone-secretagogue receptor, is a 28-amino acid peptide with a post-translational acyl modification necessary for its activity. It has central nervous system actions that affect appetite, body mass and energy balance. An intracerebroventricular (ICV) injection protocol of sub-nanomolar doses of ghrelin, known to alter the morphology of ACTH and GH producing pituicytes and plasma levels of these hormones, was used to provide an overview of metabolic changes linked to energy metabolism. Variables measured were: food intake (FI), water intake (WI), fecal mass, urine volume, body weight (BW), retroperitoneal (RP) and epididymal (EPI) white adipose tissue (WAT), and changes in serum leptin, insulin, triglycerides, cholesterol, and glucose. Five injections of rat ghrelin or PBS (n=8 per group) were given ICV every 24 h (1 microg/5 muL PBS) to adult male rats. Ghrelin had a positive and cumulative effect on FI, WI and BW (p<0.05), but not feces mass or urine volume (p>0.05). Centrally applied ghrelin clearly increased RP WAT (by 235%, p<0.001), EPI WAT (by 85%, p<0.05) and serum insulin levels (by 43%, p<0.05), and decreased serum leptin levels (by 77%, p<0.05) without (p>0.05) evoking changes in blood triglyceride cholesterol, or glucose levels. These data and the available literature clearly document that exposure of the brain of normal rats, over time, to sub-nanomolar doses of ghrelin results in metabolic dysregulation culminating in increased body mass, consummatory behavior, and lipid stores as well as changes in blood leptin/insulin levels. Thus, modulation of central ghrelin receptors may represent a pharmacological approach for controlling multiple factors involved in energy balance and obesity.

Maternal dexamethasone treatment reduces ovarian follicle number in neonatal rat offspring.

Elevated glucocorticoid levels in the gravid female circulation affect a number of endocrine functions in the fetuses and neonates. The aim of this study was to examine the effects of maternal dexamethasone (Dx) administration during late pregnancy on the ovaries of neonatal offspring. On the 16th day of pregnancy, experimental dams received subcutaneously 1.0 mg Dx/kg b.w., followed by 0.5 mg Dx/kg b.w./day on the 17th and 18th days of gestation. The control gravid females received the same volume of saline vehicle. Left ovaries from 5-day-old female pups were stereologically analyzed. The ovary volumes were estimated using Cavalieri's principle. The number of healthy and atretic primordial and primary follicles was estimated using a fractionator-physical dissector method. The number of secondary follicles was determined by exact counts of every fourth section encompassing whole cross-sections of the ovary. The ovary volume was significantly decreased (by 44.4%; P < 0.05) in the group of female pups from Dx-treated mothers comparing to the controls. The numbers of healthy primordial and atretic follicles were 38.8% (P < 0.05) and 50.9% (P < 0.05), respectively, reduced in the ovaries of pups from the Dx-treated mothers, when compared with the control values. There were 53.4% (P < 0.05) fewer healthy primary and 41.8% (P < 0.05) fewer healthy secondary follicles as well. The numbers of atretic primary and secondary follicles were reduced by 60.0% (P < 0.05) and 61.7% (P < 0.05), respectively. It can be concluded that fetal exposure to glucocorticoids decreased the pool of non-growing follicles in the neonatal ovary, whereas the processes of folliculogenesis and atresia remained unaffected.

The effects of chronic SRIH-14 and octreotide administration on the pituitary-adrenal axis in adult male rats.

The effects of chronic treatments with SRIH-14 and octreotide on pituitary corticotropes (ACTH cells) and on the adrenal cortex of male Wistar rats were examined. Adult males received two daily s.c. injections of 20 microg/100 g of body weight of either SRIH-14 or octreotide for 28 consecutive days. ACTH cells were studied using a peroxidase-antiperoxidase immunocytochemical procedure. Morpho-metry was used to evaluate the changes in cell and nuclear volumes (microm3) and volume densities (%) of ACTH-immunoreactive cells. The adrenal cortex was analyzed by histological and morphometric methods. A significant (p<0.05) decrease in body weight and in the absolute weights of the pituitary and adrenal glands was observed in both treated groups. Morphometric parameters of ACTH cells in both treated groups were not significantly (p>0.05) different than in control rats. The absolute volumes of the adrenal gland and adrenal cortex were significantly (p<0.05) decreased in both treated groups. The absolute and relative volumes of the zona glomerulosa (ZG), as well as the cellular and nuclear volumes of the ZG were significantly (p<0.05) decreased in the both treated groups. In rats treated with SRIH-14 and octreotide, the absolute and relative volumes of the zona fasciculata (ZF) and zona reticularis (ZR), as well as their stereological parameters, did not change significantly (p>0.05). The aldosterone levels in the SRIH-14 and ocreotide-treated groups were significantly (p<0.05) decreased - by 13% and 19%, respectively. The concentration of ACTH and corticosterone did not change significantly. Together, these findings show that SRIH-14 and octreotide administration affected the morphological characteristics of the adrenal ZG in a similar manner, and brought about a decrease in plasma aldosterone concentration. These treatments did not affect pituitary ACTH cells or adrenal ZF and ZR functioning.

Multiple treatments with SRIH-14 or octreotide affect adrenal zona glomerulosa in adult male rats.

Somatostatin analogues are currently used to treat various disorders such as hypersecretion and different neuroendocrine tumors. In this study we examined the effects on the adrenal cortex of somatostatin (SRIH-14) and octreotide administered subcutaneously twice daily for 5 days to adult male rats. Control rats received saline under the same regime. After sacrifice, the adrenal glands were removed and examined morphometrically using the M(42) multipurpose test system. Blood samples were prepared for biochemical tests. Both SRIH-14 and octreotide induced morphofunctional changes in adrenal zona glomerulosa. We found significant decreases (p < 0.05) in the absolute cell and nuclear volumes of zona glomerulosa in both experimental groups in comparison to the control. The serum aldosterone level was 11% lower (p < 0.05) in the SRIH-14 and 13% (p < 0.05) lower in the octreotide-treated group in comparison with the control group. Morphometric parameters of zona fasciculata and zona reticulata and corticosterone levels were not altered significantly (p > 0.05) in either treated group. It may therefore be concluded that both SRIH-14 and octreotide affected zona glomerulosa in the same manner by decreasing morphofunctional characteristics.

Microalbuminuria in children with vesicoureteral reflux.

Vesicoureteral reflux (VUR) is a common congenital anomaly of the urinary tract that may be inherited. Reflux of infected urine may cause scarring in susceptible kidneys with the potential to compromise renal function. The aim of the study was to evaluate the possible influence of different grades of VUR on glomerular damage using microalbuminuria as a parameter. Children with VUR detected by voiding cystourethrography (VCUG) were investigated. According to the grade of VUR, patients were separated into three groups. The first group included 12 children with VUR grade I-II. The second group consisted of 12 children with grade III of VUR. Patients with VUR grade IV-V (n = 11) were members of the third group. The control group consisted of 17 healthy children. Microalbuminuria was examined in samples of morning urine specimens using a microalbumin/creatinine reagent kit. Serum urea, creatinine levels and creatinine clearance (CCR) were measured as markers of renal function. The mean value of microalbumin excretion in the third group showed a statistically significant increase (p < 0.001) compared to all other groups. CCR in the third group was statistically significantly decreased (p < 0.05) in comparison to the group of healthy children. There were no statistically significant changes of microalbumin excretion and CCR in the first and second group compared to control values. We discussed the presence of microalbuminuria and decrease of CCR in children with high grade of VUR as a possible consequence of retrograde urine flow (intrarenal reflux), glomerulosclerosis, and consecutive hyperfiltration.

The effect of centrally administered ghrelin on pituitary ACTH cells and circulating ACTH and corticosterone in rats.

Ghrelin is a brain-gut peptide known for its growth hormone (GH)-releasing and appetite-inducing activities. This natural GH secretagogue (GHS) was originally purified from rat stomach, but it is expressed widely in different tissues where it may have endocrine and paracrine effects. The central effects of ghrelin on adrenocorticotropic hormone (ACTH) cells, ACTH release and subsequent corticosterone release from adrenal glands remains to be clarified. The aim of this study was to specifically determine the morphological features of ACTH-producing pituicytes and blood concentration of ACTH and corticosterone after central administration of ghrelin. Five doses of rat ghrelin or PBS (n=10 per group) were injected every 24 h (1 microg of ghrelin in 5 muL PBS), into the lateral cerebral ventricle of male rats. Results showed that ghrelin increased (p<0.05) absolute and relative pituitary weights compared to controls (58% and 41% respectively). Morphometric parameters, i.e. the volume of the ACTH cells, nuclear volume, and volume density were all increased (p<0.05), by 17%, 6% and 13%, respectively, 2 h after the last ghrelin treatment. Ghrelin increased circulating concentrations of ACTH and corticosterone (p<0.05) by 62% and 66%, respectively. The data provide clear documentation that intracerebroventricular ghrelin stimulates ACTH cell hypertrophy and proliferation, and promotes ACTH and corticosterone release. Determining the role of ghrelin in physiological stress responses and whether control of the peptide's activity would be useful for prevention and/or treatment of stress-induced diseases remain important research goals.

Influence of maternal dexamethasone treatment on morphometric characteristics of pituitary GH cells and body weight in near-term rat fetuses.

Growth hormone (GH) and glucocorticoids have a powerful influence on controlling fetal growth, differentiation and maturation of numerous tissues. In the present study, the effect of maternal dexamethasone (Dx) treatment on GH cells and body weight in 19- and 21-day-old rat fetuses was investigated using immunocytochemical and morphometric methods. Pregnant female rats received daily injections of 1.0-0.5-0.5 mg Dx/kg b.w. on days 16-18 of pregnancy (experimental group), while the control group received an equal volume of saline. Dx treatment of pregnant rats enhanced immunostaining intensity and significantly increased (p<0.05) GH nuclear and cell volume, as well as volume density and number of GH cells per square millimeter in 19-day-old fetuses compared to the controls. In 21-day-old fetuses after maternal Dx administration, immunoreactivity, volume density and number of GH cells remained significantly increased (p<0.05). Dx treatment of pregnant rats resulted in marked body weight reduction of 21-day-old but not 19 days old fetuses in comparison with the corresponding controls. The presented results demonstrate that maternal Dx application has pronounced effect on morphometric parameters of GH cells of 19- and 21-day-old fetuses. Also, in near-term rat fetuses body weight was largely independent of pituitary GH cell activity.

Leiomyoma of the uterus and retroperitoneal angioleiomyoma: case report.

Retroperitoneal angioleiomyoma is a benign mesenchymal neoplasm that is composed of smooth muscle cells and thick-walled vessels. In a 36-year-old patient a retrouterine and retroperitoneal tumor, 70 x 65 x 50 mm in size, was discovered during a surgical procedure due to uterine myoma. The tumor had a soft consistency and was completely removed. Histopathology showed features of angioleiomyoma. Angioleiomyoma is a rare benign entity; hence a benign course and good prognosis are expected.

Central effects of ghrelin on serum growth hormone and morphology of pituitary somatotropes in rats.

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, was originally purified from rat stomach; subsequently, ghrelin neurons were found in the arcuate nuclei of rats. Central effects of the peptide on GH release, however, remain to be clarified. The aim of the present study was to determine the morphologic features of GH-producing pituicytes and serum GH concentration after central administration of ghrelin. Five injections of rat ghrelin or phosphate-buffered saline (PBS; n = 10 rats/group) were given every 24 hrs (1 microg of ghrelin in 5 microl of PBS) into the lateral cerebral ventricle of male rats. Significant (P < 0.05) increases in absolute and relative pituitary weights occurred in ghrelin-treated rats versus controls (58% and 41%, respectively). Morphometric parameters (i.e., the volume of GH cells, volume of their nuclei, and volume density) all significantly (P < 0.05) increased by 17%, 18%, and 19%, respectively, in the ghrelin-treated group versus controls. Terminal serum concentration of GH was significantly (P < 0.05) increased by 15% with ghrelin treatment. The results clearly document that daily nanomolar doses of ghrelin into the lateral cerebral ventricle stimulate GH cell proliferation and promote GH release. Thus, achieving pharmacologic control of central ghrelin receptors is a promising modality to modulate the actions of GH.

Effects of ovariectomy and chronic estradiol administration on pituitary-thyroid axis in adult rats.

The effects of ovariectomy (Ovx) and of ovariectomy followed by chronic estradiol dipropionate administration (Ovx EDP) on the structure and function of the pituitary-thyroid axis were examined in the rat. Pituitary TSH cells and thyroid tissue were histologically, immunohistochemically and stereologically investigated. Serum TSH and T(4) levels were determined by RIA. Ovx did not affect pituitary weight, but subsequent treatment with EDP led to its more than two-fold increase (p<0.05). After ovariectomy, the cellular volume of pituitary TSH-immunoreactive cells increased by 28%, p<0.05 compared to sham-operated animals (SO). Treatment of Ovx rats with EDP partially reversed this change. However, the relative volume density of thyrotrophs decreased in comparison to the Ovx and SO groups (by 18% and 23%, p<0.05, respectively). No statistically significant differences in serum TSH levels were observed between the experimental groups. In thyroid tissue both peripheral and central follicles responded to Ovx and EDP treatments. Compared to SO rats, the relative volume densities of the follicles and colloid were increased (by 14% and 30%, p<0.05, respectively) in Ovx rats. Chronic EDP treatment of Ovx rats reversed these changes to the pre-ovariectomy state. Hyperplasia of thyroid follicular cells and a significant reduction (by 21%, p<0.05) of the serum level of T(4) were detected. In conclusion, estradiol deficiency and chronic treatment affected pituitary TSH cells and thyroid tissue. The sum effect of Ovx on the pituitary-thyroid axis was slightly stimulatory. Subsequent EDP treatment decreased thyroid functioning but at the same time preserved serum TSH at the control level.