Costs of dental care and its financial impacts on patients in a population with low availability of services.

OBJECTIVES: To determine the direct and indirect costs of accessing and utilizing dental services in Tanzania and the proportion of patients experiencing economic burden due to treatment costs. BASIC RESEARCH DESIGN: Survey of 489 dental patients utilizing an out-of-pocket payment modality was carried out in four regional hospitals. Direct and indirect costs for service utilization were calculated. Financial expenditures were used to assess significant financial impacts of utilization of dental services on household economies. RESULTS: Direct costs comprised 80% of the total treatment costs, whereas indirect costs comprised 20%. About half of the patients experienced significant financial impacts as a result of their utilization of dental services. Proportionately more patients from low-income households (92.2%) experienced significant financial impacts. Most patients attended the clinics due to toothache and the most widely expected treatment was dental extraction. Only 7.1% of the patients received a filling. The costs for dental restorations were three-times those for tooth extraction. CONCLUSIONS: Dental service utilization leads to significant financial impacts on many of the households in this setting. Increasing the rate of prepayment for health services and reducing income inequality may help to mitigate these impacts.

Patients' willingness to pay for dental services in a population with limited restorative services.

OBJECTIVES: To determine and compare patients' willingness-to-pay (WTP) for tooth extraction and filling services in Tanzania and to assess the socio-demographic factors that are associated with such valuations. METHODS: Contingent valuation survey utilizing an open-ended willingness-to-pay format was administered among 1522 outpatients in four regional hospitals in Tanzania. WTP for extraction and tooth filling services for various tooth categories were determined and compared using Mann-Whitney and Kruskal-Wallis tests. The association of WTP values with socio-demographic background factors was assessed using multiple regression analysis. RESULTS: The mean WTP amounts for tooth filling were Tanzania shillings (Tshs) 7,398 (3.4 US$) and Tshs 7,726 (3.5 US$) for anterior and posterior teeth respectively. The mean WTP for tooth filling services was lower than the average charged fees in dental facilities. The mean WTP amounts for tooth extraction were Tshs 5,448 (2.5 US$) and Tshs 6,188 (2.8 US$) for anterior and posterior teeth respectively. WTP amounts were shown to vary by age, income, outpatient status and previous experience with the dental services. Belonging in youngest age group (18-24 years) and having a high-income level was associated with increased odds for high WTP valuations irrespective of tooth and treatment types. CONCLUSIONS: WTP reveals a preference for tooth filling rather than extraction services in this population. More studies are needed to address the discrepancy between the stated preferences and utilization patterns for dental services.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

BACKGROUND: An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. METHODS: The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. RESULTS: Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P < 0·001). When the age and sex of the patient as well as the hospital were controlled for simultaneously, the operative treatment generated significantly more costs in all models. CONCLUSION: Patients receiving antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery.

Measuring the economic value of morning stiffness: consistency over 1 year.

OBJECTIVES: The aims of this study were to determine the within-patient variation in the duration of morning stiffness (MS) over 1 year and the corresponding monetary equivalents assigned to its changes using the willingness-to-pay (WTP) methodology. METHOD: A sample of 100 patients with rheumatoid arthritis (RA) was drawn from the register of the Hospital District of Southwest Finland. Subjects were interviewed by telephone on recruitment and 1 year later, using the same structured questionnaire. The subjects were asked to estimate in minutes the typical duration of their MS during the previous week. Sociodemographic background data and subjects' WTP for a 25, 50, 75, and 100% reduction in MS duration were requested, and years with RA diagnosis and serological data were obtained from hospital records. RESULTS: After 1 year, there was a reduction in average MS duration from 44.7 min to 39.0 min (ns); duration was reduced in 35% of patients, unchanged in 35%, and prolonged in 30%. Changes in MS duration were reflected by within-patient variation in WTP estimates. In linear regression models, change in duration of MS significantly (p < 0.03) explained the variation in change of WTP for symptom reduction. CONCLUSIONS: WTP methodology produces consistent monetary values to assess the relative values patients with RA place on reduction in duration of MS.

Productivity benchmarks for operative service units.

BACKGROUND: Easily accessible reliable information is crucial for strategic and tactical decision-making on operative processes. We report development of an analysis tool and resulting metrics for benchmarking purposes at a Finnish university hospital. METHODS: The analysis tool is based on data collected in a resource management system and an in-house cost-reporting database. RESULTS: The exercise reports key metrics for four operative service units and six surgical units from 2014 and the change from year 2013. Productivity, measured as total costs per total hours, ranged from 658 to 957 €/h and utilization of the total available resource hours at the service unit level ranged from 66% to 74%. The lowest costs were in a unit running only regular working hour shifts, whereas the highest costs were in a unit operating on 24/7 basis. The tool includes additional metrics on operating room (OR) scheduling and monthly data to support more detailed analysis. CONCLUSION: This report provides the hospital management with an improved and detailed overview of its operative service units and the surgical process and related costs. The operating costs are associated with on call duties, size of operative service units, and the requirements of the surgeries. This information aids in making mid- to long range decisions on managing OR capacity.

Consistency of assessments and willingness to pay for a reduction in morning symptoms over time in patients with rheumatoid arthritis.

OBJECTIVES: To determine the variation in morning symptoms and in the corresponding monetary equivalents assigned to their reduction. METHODS: The sampled (n = 100) rheumatoid arthritis (RA) patients were interviewed twice by a trained interviewer using the same interview, 2 weeks apart. Patients assessed fatigue, pain, and severity of morning stiffness (MS) on waking up and after maximum improvement on a numeric rating scale (NRS). Patients estimated the duration of MS in minutes and reported the number of tender and swollen joints. Patients were also asked to estimate how much they would be willing to pay on a daily basis if pain, duration of MS, and severity of MS when waking up could be reduced by 25, 50, 75, and 100%. Weighted averages of the monetary assessments for symptom reduction were computed. RESULTS: On average, the NRS values at the first and second assessments were close to each other, except for fatigue and pain, which were significantly lower (p < 0.01) in the second assessment. There was limited within-patient variation, with the majority of symptom assessments within a range of ±10%. Weighted average willingness-to-pay (WTP) estimates were consistent across time points for reduction in pain and MS severity and duration. Changes in symptom assessments were reflected in the WTP estimates. CONCLUSIONS: The duration and severity of MS seemed to be more consistent over time than pain and fatigue. WTP estimates and their changes corresponded closely to changes in symptom assessments.

[Effect of alpha-conotoxin MII and its N-terminal derivatives on Ca2+ and Na+ signals induced by nicotine in neuroblastoma cell line SH-SY5Y].

Nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation ofintracellular Ca2+-dependent processes in cells both in normal and pathological states, alpha-Conotoxins isolated from Conus snails venom are a valuable tool for the study of pharmacological properties and functional role of nAChRs. In the present study the alpha-conotoxin MII analogue with the additional tyrosine attached to the N terminus (Y0-MII) was prepared. Also we synthesized analogs with the N-terminal glycine residue labeled with the Bolton- Hunter reagent (BH-MII) or fluorestsein isothiocyanate (FITC-MII). Fluorescence microscopy studies of the neuroblastoma SH-SY5Y cells loaded with Ca2+ indicator Fura-2 or with Ca2+ and Na+ indicators Fluo-4 and SBFI were performed to examine effect of MII modification on its ability to inhibit nicotin-induced increases in intracellular free Ca2+ and Na+ concentrations ([Ca2+] and [Na+]i respectively). Monitoring of individual cell [Ca2+]i and [Na+]i signals revealed different kinetics of [Ca2+]i and [Na+]i rise and decay in responses to brief nicotine (Nic) applications (10-30 microM, 3-5 min), which indicates to different mechanisms of Ca2+ and Na+ homeostasis control in SH-SY5Y cells. MII inhibited in concentration-dependent manner the both [Ca2+]i and [Na+]i increase induced by Nic. Additional tyrosine in the Y0-MII or, especially, more sizeable label in FITC-MII significantly reduced the inhibitory effect of MII. Whereas the efficiency of the Ca2+ response inhibition by BH-MII was found to be close to the efficiency of its inhibition by natural alpha-conotoxin MII, radioiodinated derivatives BH-MII can be used in radioligand assay.

The prevalence and consequences of abdominal rectus muscle diastasis among Finnish women: an epidemiological cohort study.

PURPOSE: Post-pregnancy abdominal rectus diastasis (ARD) has raised attention in the field of surgery in recent years, but there is no consensus about when to consider surgery. Our aim was to find out what is the normal inter-rectus distance in fertile aged, female population in Finland and to examine whether there is a linea alba width that would predispose to diastasis-related problems after pregnancy. METHODS: For this prospective cohort study, women participating early pregnancy ultrasound in Helsinki University Hospital Department of Obstetrics and Gynecology during 1.1.2018-8.3.2019, were recruited. The width of linea alba was measured by ultrasound during the early pregnancy ultrasound. Symptoms were measured by questionnaire including Health-Related Quality of Life (RAND-36) and Oswestry Disability Index for back symptoms and disability. RESULTS: Linea alba width was measured in total of 933 women. The average inter-rectus distance (IRD) among nulliparous women was 1.81 ± 0.72 cm. After one previous pregnancy, the average linea alba width was 2.36 cm ± 0.83 cm and after more pregnancies 2.55 ± 1.09 cm. There was a positive correlation between previous pregnancies and the increased linea alba width (p = 0.00004). We did not perceive any threshold value of linea alba width that would predispose to back pain or movement control problems in this cohort, in which severe diastasis (over 5 cm) was rare. CONCLUSION: Mean inter-rectus distance in parous population exceeds stated normative values. Moderate ARD (3.0-5.0 cm) alone does not seem to explain low back pain or functional disability in population level. Severe post-pregnancy diastasis (over 5.0 cm) is rare.

How much is a reduction in morning stiffness worth to patients with rheumatoid arthritis?

OBJECTIVE: The aim of this study was to determine the monetary equivalent of the emotional and functional impact of morning stiffness (MS) in patients with rheumatoid arthritis (RA), using alternative valuing methods. METHODS: Telephone interviews were conducted among 166 patients with RA to assess utility and clinical symptoms, including MS. Three standard economic methods were used: the human capital approach (HCA), marginal value of time (MVT), and willingness-to-pay (WTP). RESULTS: The monetary equivalent of the impact of MS varied with the method used (from EUR 5.74 to EUR 17.87 per patient per day) and severity of MS (5-8-fold higher in patients with severe MS compared with mild MS). Patients placed considerable value on a reduction in duration and severity of MS. Patients with MS lasting an hour or more were willing to pay EUR 21.74/day to stop the symptom and EUR 10.63/day to halve the duration. Patients with severe MS were willing to pay EUR 47.86/day to stop the symptom and EUR 21.68/day to halve the severity. CONCLUSIONS: The observed variation in the monetary equivalent of the impact of MS obtained with the three estimation methods indicates that the findings of studies using different valuing methods should not be compared directly. The study demonstrates that a reduction in MS is worth a considerable amount to patients with RA, particularly those with severe or prolonged MS. These findings suggest that clinical treatment decisions to improve patients' quality of life should also incorporate therapy that reduces MS.

Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor.

Glial cell line-derived neurotrophic factor (GDNF) and a related protein, neurturin (NTN), require a GPI-linked coreceptor, either GFR alpha1 or GFR alpha2, for signaling via the transmembrane Ret tyrosine kinase. We show that mice lacking functional GFR alpha2 coreceptor (Gfra2-/-) are viable and fertile but have dry eyes and grow poorly after weaning, presumably due to malnutrition. While the sympathetic innervation appeared normal, the parasympathetic cholinergic innervation was almost absent in the lacrimal and salivary glands and severely reduced in the small bowel. Neurite outgrowth and trophic effects of NTN at low concentrations were lacking in Gfra2-/- trigeminal neurons in vitro, whereas responses to GDNF were similar between the genotypes. Thus, GFR alpha2 is a physiological NTN receptor, essential for the development of specific postganglionic parasympathetic neurons.

Protein kinase C -activating isophthalate derivatives mitigate Alzheimer's disease-related cellular alterations.

Abnormal protein kinase C (PKC) function contributes to many pathophysiological processes relevant for Alzheimer's disease (AD), such as amyloid precursor protein (APP) processing. Phorbol esters and other PKC activators have been demonstrated to enhance the secretion of soluble APPα (sAPPα), reduce the levels of ß-amyloid (Aß), induce synaptogenesis, and promote neuroprotection. We have previously described isophthalate derivatives as a structurally simple family of PKC activators. Here, we characterised the effects of isophthalate derivatives HMI-1a3 and HMI-1b11 on neuronal viability, neuroinflammatory response, processing of APP and dendritic spine density and morphology in in vitro. HMI-1a3 increased the viability of embryonic primary cortical neurons and decreased the production of the pro-inflammatory mediator TNFα, but not that of nitric oxide, in mouse neuron-BV2 microglia co-cultures upon LPS- and IFN-γ-induced neuroinflammation. Furthermore, both HMI-1a3 and HMI-1b11 increased the levels of sAPPα relative to total sAPP and the ratio of Aß42/Aß40 in human SH-SY5Y neuroblastoma cells. Finally, bryostatin-1, but not HMI-1a3, increased the number of mushroom spines in proportion to total spine density in mature mouse hippocampal neuron cultures. These results suggest that the PKC activator HMI-1a3 exerts neuroprotective functions in the in vitro models relevant for AD by reducing the production of TNFα and increasing the secretion of neuroprotective sAPPα.

Carcinogenicity of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the rat.

BACKGROUND: Several epidemiologic studies have suggested that the consumption of chlorinated drinking water may be associated with the development of certain cancers in humans. 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a byproduct of the chemical reactions that occur in chlorinated drinking water, has been found to be mutagenic in bacteria and mammalian cells; however, its potential to cause tumors in animals has not been tested previously. PURPOSE: The objective of this study was to evaluate the carcinogenicity of MX in rats given MX in their drinking water. METHODS: MX was administered to male and female Wistar rats (50 rats per dose group) in drinking water for 104 weeks at concentrations yielding the average daily doses of MX of 0.4 mg/kg of animal weight (low dose), 1.3 mg/kg (mid dose), and 5.0 mg/kg (high dose) for males and 0.6 mg/kg, 1.9 mg/kg, and 6.6 mg/kg for females, respectively. Control rats received water from the same source used for preparation of the MX dose formulations (after its adjustment to the same pH range). Body weight, clinical signs, and food and water consumption were recorded regularly. At the end of the treatment period, the animals were killed and full histopathologic analysis was performed on 47 tissues and all lesions. RESULTS: Dose-dependent increases in tumor incidence were observed in rats given MX-containing drinking water; the same MX doses had no obvious toxic effects on animals. MX consumption increased most drastically the prevalence of follicular adenoma (up to 43% and 72% in high-dose males and females, a test [one-sided] for positive trend in all dose groups P = .0045 and P = .0000, respectively) and carcinoma (55% [P = .0000] and 44% [P = .0000], respectively) in thyroid glands and cholangioma in the liver (8% [P = .0009] and 66% [P = .0000] in the high-dose males and females, respectively). Among rats given the higher doses of MX in their drinking water, cortical adenomas of the adrenal glands were increased in both sexes, alveolar and bronchiolar adenomas of the lungs and Langerhans' cell adenomas of the pancreas were increased in males, and lymphomas, leukemias, and adenocarcinomas and fibroadenomas of the mammary glands were increased in females. Even the lowest MX dose studied was carcinogenic. CONCLUSION: MX is a potent carcinogen in both male and female rats, and it causes tumors at doses that are not overtly toxic to rats. IMPLICATIONS: Although these findings cannot be extrapolated to humans, MX should be studied as a candidate risk factor in the possible association between consumption of chlorinated drinking water and cancer in humans.

Labelling, molecular modelling and biological evaluation of vardenafil: a potential agent for diagnostic evaluation of erectile dysfunction.

99mTc-tricarbonyl-vardenafil was specifically radiosynthesized for diagnostic evaluation of erectile dysfunction with a radiochemical yield ~97.2%. It was stable in saline up to 15h and in serum for more than 6h. The radiocomplex was lipophilic with a partition coefficient ~1.32 and plasma protein binding 72-76%. Its structure was determined using molecular mechanics and confirmed by NMR. In-silico docking to its target PDE5 enzyme was performed. The radiocomplex inhibitory activity was assessed and its IC50 was 0.7nM. Biodistribution in normal rats and biological evaluation in rat models of erectile dysfunction were performed. The results strongly suggested that 99mTc-tricarbonyl-vardenafil is a good candidate to image erectile dysfunction in humans.

Stimulation of adrenal medullary cells in vivo and in vitro induces expression of c-fos proto-oncogene.

The nuclear proto-oncogene, c-fos, has been implicated in the coordinated regulation of gene expression during cell proliferation and differentiation. In this study, we have demonstrated the induction of the c-fos gene products in differentiated cells of the adrenal medulla by non-mitogenic signals. Activation of adrenal medullary cells in vivo by insulin-induced hypoglycemia, and in vitro by nicotine or angiotensin resulted in the rapid and transient elevation of c-fos mRNA levels. Induction of the c-fos mRNA by angiotensin and nicotine were accompanied by the appearance of the c-fos protein. The increase in c-fos protein occurred initially in the cytoplasm and, later, in the nucleus, and it was co-localized with tyrosine hydroxylase. Nuclear expression of the c-fos protein was also induced by veratridine, forskolin and the calcium ionophore A231287. The role of calcium in the regulation of the c-fos gene by angiotensin with nifedipine and inhibition of the effects of angiotensin with nifedipine and sphingosine, a protein kinase C inhibitor. Activation of the c-fos gene may play a role in the coordinated induction of genes involved in the long-term adaptation of adrenal medullary cells to increased functional demands.

Role of protein kinase C in microglia-induced neurotoxicity in mesencephalic cultures.

Microglial activation selectively kills certain neuron populations in mixed neuronal/glial cultures, which may prove useful for modeling neurodegenerative diseases such as Parkinson's disease. In mesencephalic mixed neuronal/glial cultures, microglial activation by zymosan A killed more dopaminergic neurons, assessed by [3H]dopamine uptake and by counting tyrosine hydroxylase-immunoreactive neuron number, than did microglial activation by lipopolysaccharide (LPS). The additional toxicity of zymosan resulted from microglial protein kinase C (PKC) activation. Both zymosan and PMA, but not LPS, activated PKC in enriched microglial preparations. In the mixed neuronal/glial cultures, activation of PKC by phorbol myristate acetate (PMA) increased LPS-induced nitric oxide (NO; by nitrite measurements), but not zymosan-induced NO production, and increased LPS-induced dopaminergic neurotoxicity, but not zymosan-induced dopaminergic neurotoxicity. Additive effects of PMA and LPS, similar to zymosan effects alone, reflected activation of distinct neurotoxic pathways in the microglia. The NO synthase inhibitor N-nitro-L-arginine methyl ester (NAME) totally blocked the neurotoxicity of LPS, and partially blocked zymosan-induced neurotoxicity; NAME did not block the PKC component of neurotoxicity. In addition to stimulating NO production as effectively as LPS, zymosan also activates microglial PKC and associated non-NO-mediated neurotoxic pathways that may be important in human neurodegenerative diseases. Since the role of NO in human microglia-induced neurotoxicity is controversial, zymosan may prove more useful than LPS as a microglial activator in the rodent mixed neuronal/glial culture model.

Development of tolerance to the hormonal effects of morphine without changes in the aminergic functions in the brain of the rat.

The effect of morphine on cold-stimulated secretion of TSH and prolactin was studied in male rats, both in acute studies and after the chronic administration of morphine for 14 days (twice a day with increasing doses). The duration of the stimulatory effect of a single dose of morphine on secretion of prolactin was shorter (less than 2 hr) than its inhibitory effect on cold-stimulated secretion of TSH (over 2 hr). In the rats pretreated with morphine, a tolerance to the depressant effect of TSH of the challenge dose of morphine was seen at 2 hr but not at 1 hr after the injection. In contrast, a tolerance to the stimulatory effect of morphine on prolactin was seen at 1 hr after the acute dose of morphine. The minor alterations of the hypothalamic amine neurotransmitters and their metabolites did not correlate with the hormonal responses or to the development of tolerance.

Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat.

1. We compared three new catechol O-methyltransferase (COMT) inhibitors (OR-611, Ro 40-7592 and CGP 28014; 10 and 30 mg kg-1, i.p.) in male rats given levodopa (L-DOPA, 50 mg kg-1, i.p.) and carbidopa ((-)-L-alpha-methyl dopa, 50 mg kg-1, i.p.). In some studies pretreatment with pargyline (80 mg kg-1, i.p.) was used to block the function of monoamine oxidase (MAO). 2. Decreases of hypothalamic and striatal 3-O-methyl-dopa (3-OMD) levels were used as measures of the inhibition of peripheral COMT. The inhibition of brain COMT activity was estimated by decreases of hypothalamic and striatal homovanillic acid (HVA) and 3-methoxytyramine (3-MT; after pargyline) levels. 3. The three COMT inhibitors studied had different individual characteristics. OR-611 was primarily a peripherally acting COMT inhibitor, decreasing 3-OMD levels in the striatum (to 31-52%) and in the hypothalamus (to 16-27%) both in the control and pargyline-treated animals at 1 and 3 h. It did not have any effect on brain HVA and 3-MT. 3. Ro 40-7592 was a broad spectrum COMT inhibitor decreasing striatal and hypothalamic 3-OMD (always to less than 30%), HVA (to less than 50%) and 3-MT levels (to less than 23%) significantly both at 1 and 3 h. It was more potent than OR-611. 4. CGP 28014 functioned as a weak COMT inhibitor in the periphery inhibiting 3-OMD formation only at 3 h. In contrast, it was fairly potent in decreasing the brain HVA and 3-MT levels at 1 h (to 37-22% and 42-35% in the striatum, and to 57-33% and 64-35% in the hypothalamus, respectively) but not at 3 h. Since CGP 28014, unlike OR-611 and Ro 40-7592, did not generally increase the brain DOPA, dopamine or DOPAC levels, it was not a typical COMT inhibitor.

Effect of acute nicotine administration on striatal dopamine output and metabolism in rats kept at different ambient temperatures.

1. The effect of ambient temperature on the nicotine-induced (0.3, 0.5 or 0.8 mg kg(-1) s.c.) changes of the striatal concentrations of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied in freely-moving rats by in vivo microdialysis. 2. At the ambient temperature of 30 - 33 degrees C, but not at 20 - 23 degrees C, nicotine doses of 0.5 (P<0. 01) and 0.8 mg kg(-1) (P<0.05) significantly increased the extracellular DA concentration. The nicotine doses of 0.5 and 0.8 mg kg(-1) increased the DA metabolite levels similarly at both ambient temperatures studied (P

Effect of modified brain histamine contents on prolactin and thyrotropin secretion in male rats.

Effects of modified brain histamine contents on thyrotropin and prolactin secretion were studied in male rats. Under basal conditions the histamine content in the hypothalamus was approximately 8-10-fold higher than that in the striatum and the rest of the brain. L-histidine (1000 mg/kg, ip), a histamine precursor, and metoprine (20 mg/kg, ip), an inhibitor of histamine methyltransferase, elevated histamine content in the brain by 65% and 167%, respectively. When the treatments were given together an additive effect (119-250% increase) on brain histamine was observed. Metoprine significantly decreased serum prolactin levels, while L-histidine had no effect. This effect of metoprine was not modified by treatment with L-histidine. Thus, metoprine has an inhibitory effect on prolactin secretion that is not related to elevated brain histamine contents. The increased brain histamine content after L-histidine treatment had no effect on prolactin secretion. Basal levels of serum thyrotropin were decreased by both L-histidine and metoprine, L-histidine being more potent. In rats treated with alpha-fluoromethylhistidine, an inhibitor of L-histidine decarboxylase, the cold-induced (rats kept for 60 min at +4 degrees C) thyrotropin secretion was increased while the stress-induced prolactin secretion was decreased. In these rats, metoprine did not affect thyrotropin release but blunted the prolactin response. In conclusion, endogenous histamine inhibits thyrotropin secretion but does not affect prolactin release. Owing to its other effects, metoprine is not suitable as a tool to elevate endogenous histamine contents in the brain, at least when the regulation of anterior pituitary hormone release is being studied.

Effect of nitecapone and clorgyline, given intracerebro-ventricularly on L-dopa metabolism in the rat brain.

A new COMT inhibitor, nitecapone (OR-462) or clorgyline, a MAO-A inhibitor, was infused into the 3rd brain ventricle (i.c.v.) of conscious male rats. None of the enzyme inhibitors given alone alter hypothalamic or striatal levels of L-dopa, dopamine or their metabolites. Most of the rats were pretreated with levodopa/carbidopa (LD/CD, 15/30 mg kg-1 intraperitoneally). Now, the action of nitecapone is localized in the hypothalamus since homovanillic acid (HVA) is decreased there, not in the striatum. The levels of 3-O-methyldopa (3-OMD) are not changed in either brain region, suggesting a lack of the peripheral leakage of nitecapone. Clorgyline (3 and 10 micrograms rat-1) elevates hypothalamic and dopamine levels. Nitecapone and clorgyline decrease prolactin (PRL) levels below those reduced by LD/CD treatment.