Nitrous oxide occupational exposure in conscious sedation procedures in dental ambulatories: a pilot retrospective observational study in an Italian pediatric hospital.

BACKGROUND: Nitrous oxide has a proven clinical efficacy in conscious sedation. At certain environmental concentrations it may pose a health risk to chronically exposed healthcare workers. The present pilot study aims at evaluating the exposure to nitrous oxide of dental ambulatory personnel of a pediatric hospital. METHODS: A descriptive study design was conducted in two phases: a bibliographic analysis on the environmental safety policies and a gas concentration analysis in the dental ambulatories of a pediatric hospital, detected every 6 months from December 2013 to February 2017 according to law provisions. The surveys were carried out using for gas analysis a photoacoustic spectrometer Innova-B&K "Multi-gas monitor model 1312" and Innova-B&K "Multi-sampler model 1309". The biological analysis and monitoring have been carried out on staff urine. RESULTS: The analyses were performed during 11 dental outpatient sessions on pediatric patients. All the patients were submitted to the same dental procedures, conservative care and dental extractions. The pediatric patients were 47 (23 males, 24 females; age range 3-17 years; mean age 6,63, SD ± 2,69) for a mean of 4,27 (SD ± 1,49) per session., The mean environmental concentration of nitrous oxide during the sessions was 24.7 ppm (SD ±16,16). A correlation was found between urinary nitrous oxide concentration of dentists (Pearson's correlation 0.786; p = 0.007) and dental assistants urines (Pearson's correlation 0.918; p < 0.001) and environmental concentrations of nitrous oxide. Weak negative correlations were found between age and sex of patients and environmental concentrations of nitrous oxide. The mean values of the biological monitoring data referring to all the outpatient sessions are lower than the reference values foreseen in accordance to the regulations in force on nitrous oxide concentration. CONCLUSIONS: The mean environmental concentration values recorded in our study are below the limit of 50 ppm considered as a reference point, a value lower than those reported in other similar surveys. The results of the present study provide a contribution to the need to implement technical standards, criteria and system requirements for the dental ambulatories, to date not yet completely defined, and cannot be assimilated to the ones established for the surgical rooms.

Factors influencing plasma transfusion practices in paediatric intensive care units around the world.

BACKGROUND AND OBJECTIVES: Plasma transfusions are a frequent treatment worldwide, but many studies have reported a wide variation in the indications to transfuse. Recently, an international paediatric study also showed wide variation in frequency in the use of plasma transfusions: 25% of the centres transfused plasma to >5% of their patients, whereas another 25% transfused plasma to <1% of their patients. The objective of this study was to explore the factors associated with different plasma transfusion practices in these centres. MATERIALS AND METHODS: Online survey sent to the local investigators of the 101 participating centres, in February 2016. Four areas were explored: beliefs regarding plasma transfusion, patients' case-mix in each unit, unit's characteristics, and local blood product transfusion policies and processes. RESULTS: The response rate was 82% (83/101). 43% of the respondents believed that plasma transfusions can arrest bleeding, whereas 27% believe that plasma transfusion can prevent bleeding. Centres with the highest plasma transfusion rate were more likely to think that hypovolaemia and mildly abnormal coagulation tests are appropriate indications for plasma transfusions (P = 0·02 and P = 0·04, respectively). Case-mix, centre characteristics or local transfusion services were not identified as significant relevant factors. CONCLUSION: Factors influencing plasma transfusion practices reflect beliefs about indications and the efficacy of transfusion in the prevention and management of bleeding as well as effects on coagulation tests. Educational and other initiatives to target these beliefs should be the focus of research.

Diabetes may affect the expression of matrix metalloproteinases and their inhibitors more than smoking in chronic periodontitis.

BACKGROUND AND OBJECTIVE: No previous study has directly compared the levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) between smokers and individuals with diabetes mellitus (DM) with periodontitis. Therefore, the aim of this study was to evaluate the gene expression of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 in tissues with chronic periodontitis (ChP) of smokers and individuals with type 2 DM. MATERIAL AND METHODS: Gingival biopsies were harvested from: non-smokers and non-diabetic individuals with ChP (n = 18) (ChP group); non-diabetic smokers (≥ 10 cigarettes per day for at least the past 5 years) with ChP (n = 18) (SChP group); non-smoking individuals with type 2 diabetes (glycated hemoglobin levels ≥ 7.5%) and ChP (n = 18) (DMChP group). The tissue levels of mRNA of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 were evaluated by quantitative real-time polymerase chain reaction. RESULTS: The MMP-8 expression was the lowest in the ChP group (p < 0.05). The DMChP group presented increased mRNA levels of MMP-2 and MMP-9, when compared to the SChP group (p < 0.05). MMP-1 expression and the MMP-1/TIMP-1, MMP-2/TIMP-1, MMP-8/TIMP-1, MMP-9/TIMP-1, MMP-1/TIMP-2 and MMP-2/TIMP-2 ratios were higher in the DMChP group than in the ChP and SChP groups (p < 0.05). The DMChP group presented lower mRNA levels of TIMP-1 than the ChP group (p < 0.05). The MMP-8/TIMP-2 ratio was the highest in the SChP group (p < 0.05). CONCLUSION: Uncontrolled type 2 DM upregulates the ratio of MMP/TIMPs in sites with ChP more than smoking, which may contribute to a greater extracellular matrix degradation and periodontal breakdown in DM-related periodontitis.

Detection of Epstein-Barr virus in leucoreduced blood products.

This study examined the prevalence of three human herpesviruses (HHV), namely HHV-4 (Epstein-Barr virus/EBV), HHV-6b and HHV-7 in leucoreduced blood products obtained from the Sainte-Justine Hospital blood bank. A total of 100 specimens, including 34 red blood cell concentrates, 33 platelet bags and 33 plasma units, were collected and screened by a sensitive PCR assay using virus-specific primers. Positive units were then retested by quantitative PCR. Of the 100 specimens, one platelet unit tested positive for EBV.

Incidence of hypotension and acute hypotensive transfusion reactions following platelet concentrate transfusions.

BACKGROUND AND OBJECTIVES: Platelet concentrates (PCs) are associated with transfusion reactions involving hypotension, particularly bradykinin-mediated acute hypotensive transfusion reactions. This study aims to determine the incidence of hypotensive events and more specifically acute hypotensive transfusion reaction associated with PC transfusions. We also sought to ascertain whether these reactions are associated with elevated bradykinin levels. MATERIALS AND METHODS: This is a prospective descriptive study of PCs administered at Sainte-Justine Hospital over 28 months. All PCs administered during this period were screened for hypotension through review of all transfusion-associated reaction reports (TARRs) sent to the blood bank. All residual PC bags were returned to the blood bank. TARRs associated with hypotension were reviewed by adjudicators that established the imputability of the PC transfusion to the reaction. Bradykinin levels were sampled in the first 168 PC bags returned to the blood bank. Levels were compared between PCs associated with hypotension and control PCs not associated with hypotension. RESULTS: A total of 3672 PC bags were returned to the blood bank; 25 PCs were associated with hypotension. Adjudicators ascertained that five hypotensive events were imputable to PCs of which one was an acute hypotensive transfusion reaction (incidence: 0·03%). Bradykinin level in the latter PC was 10 pg/ml, whereas levels were 226·2 ± 1252 pg/ml in the 143 control PCs. CONCLUSION: Our results show a low incidence of hypotension after PC transfusion. We identified only one acute hypotensive transfusion reaction. No correlation between bradykinin level and the occurrence of acute hypotensive reactions could be observed given that only one event was identified.

There is no cephalocaudal gradient of computed tomography densities or lung behavior in supine patients with acute respiratory distress syndrome.

BACKGROUND: There is debate whether pressure transmission within the lungs and alveolar collapse follow a hydrostatic pattern or the compression exerted by the weight of the heart and the diaphragm causes collapse localized in the areas adjacent to these structures. The second hypothesis proposes the existence of a cephalocaudal gradient in alveolar collapse. We aimed to define whether or not lung density and collapse follow a 'liquid-like' pattern with homogeneous isogravitational layers along the cephalocaudal axis in acute respiratory distress syndrome lungs. METHODS: Acute respiratory distress syndrome patients were submitted to full lung computed tomography scans at positive end-expiratory pressure (PEEP) zero (before) and 25 cmH2 O after a maximum-recruitment maneuver. PEEP was then decreased by 2 cmH2 O every 4 min, and a semi-complete scan performed at the end of each PEEP step. RESULTS: Lung densities were homogeneous within each lung layer. Lung density increased along the ventrodorsal axis toward the dorsal region (ß = 0.49, P < 0.001), while there was no increase, but rather a slight decrease, toward the diaphragm along the cephalocaudal axis and toward the heart. Higher PEEP attenuated density gradients. At PEEP 18 cmH2 O, dependent lung regions started to collapse massively, while best compliance was only reached at a lower PEEP. CONCLUSIONS: We could not detect cephalocaudal gradients in lung densities or in alveolar collapse. Likely, external pressures applied on the lung by the chest wall, organs, and effusions are transmitted throughout the lung in a hydrostatic pattern with homogeneous consequences at each isogravitational layer. A single cross-sectional image of the lung could fully represent the heterogeneous mechanical properties of dependent and non-dependent lung regions.

Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi.

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.

Bone health and body composition in prostate cancer: Meet-URO and AIOM consensus about prevention and management strategies.

BACKGROUND: Prostate cancer (PCa) treatments are associated with a detrimental impact on bone health (BH) and body composition. However, the evidence on these issues is limited and contradictory. This consensus, based on the Delphi method, provides further guidance on BH management in PCa. MATERIALS AND METHODS: In May 2023, a survey made up of 37 questions and 74 statements was developed by a group of oncologists and endocrinologists with expertise in PCa and BH. In June 2023, 67 selected Italian experts, belonging to the Italian scientific societies Italian Association of Medical Oncology and Italian Network for Research in Urologic-Oncology (Meet-URO), were invited by e-mail to complete it, rating their strength of agreement with each statement on a 5-point scale. An agreement ≥75% defined the statement as accepted. RESULTS: In non-metastatic hormone-sensitive PCa, the panel agreed that androgen deprivation therapy (ADT) alone implies sufficient fracture risk to warrant antifracture therapy with bone-targeting agents (BTAs) for cancer treatment-induced bone loss (CTIBL) prevention (79%). Therefore, no consensus was reached (48%) for the treatment with BTAs of patients receiving short-term ADT (<6 months). All patients receiving active treatment for metastatic hormone-sensitive PCa (75%), non-metastatic castration-resistant PCa (89%) and metastatic castration-resistant PCa (mCRPC) without bone metastases (84%) should be treated with BTAs at the doses and schedule for CTIBL prevention. All mCRPC patients with bone metastasis should be treated with BTAs to reduce skeletal-related events (94%). In all settings, the panel analyzed the type and timing of treatments and examinations to carry out for BH monitoring. The panel agreed on the higher risk of sarcopenic obesity of these patients and its correlation with bone fragility. CONCLUSIONS: This consensus highlights areas lacking major agreement, like non-metastatic hormone-sensitive prostate cancer patients undergoing short-term ADT. Evaluation of these issues in prospective clinical trials and identification of early biomarkers of bone loss are particularly urgent.

Association between plasma transfusions and clinical outcome in critically ill children: a prospective observational study.

BACKGROUND AND OBJECTIVES: Plasma transfusions are commonly used in adult and paediatric intensive care units. Recent data suggest an association between plasma transfusions and worse clinical outcome in adult trauma patients. To date, no prospective paediatric study has addressed this issue. Our objective was to prospectively analyse the association between plasma transfusions and clinical outcome of critically ill children. MATERIALS AND METHODS: Prospective, observational and single centre study that includes all consecutive admissions to a tertiary level multidisciplinary paediatric critical care unit over a 1-year period. The primary outcome measure was the incidence after transfusion of new or progressive multiple organ dysfunction syndrome. Secondary outcome measures included nosocomial infections, intensive care unit length of stay and 28-day mortality. Odds ratios were adjusted for weight, severity of illness, coagulopathy, plasma transfusions prior to admission, need for extracorporeal life support and transfusion of other labile blood products. RESULTS: A total of 831 patients were enrolled, among which 94 (11%) received at least one plasma transfusion. In the latter group of patients, the adjusted odds ratio for an increased incidence of new or progressive multiple organ dysfunction syndrome was 3.2 (P = 0.002). There was also a significant difference in the occurrence of nosocomial infections and intensive care unit length of stay, but no significant difference in the 28-day mortality. CONCLUSIONS: In critically ill children, plasma transfusions seem to be independently associated with an increased occurrence of new or progressive multiple organ dysfunction syndrome, nosocomial infections and prolonged length of stay.

Survey of Oral Hygiene Habits and Knowledge among School Children: a cross-sectional study from Italy.

AIM: This study is aimed to investigate the oral hygiene practice, knowledge and attitude of young adults, assessing their awareness about the impact of a certain "risk" behaviour on their oral and dental health. MATERIALS: This is a cross-sectional survey study conducted on 829 students (350 males and 479 females, mean age 13-20 years) attending high school in Milan and surrounding areas. They were asked to complete anonymous questionnaire during the first semester of the 2019-2020 school year, under the supervision of a teacher and/or an assigned interviewer. The questionnaire was created by "Laboratorio Adolescenza", in collaboration with the International Alliance of Responsible Drinking (IARD) Research Institute and the University of Milan. All of the data was compiled into table or graph form and analysed. CONCLUSION: There is a general awareness among Italian school children about the risks of bad oral habits, however, there is a need to improve the oral health knowledge, attitude and practices in the target population with emphasis on improvement of oral hygiene practices.

[Risk of non-coherent optical radiation in the operating room]. / Rischio da radiazioni ottiche artificiali non coerenti in sala operatoria.

In this study, we evaluated the exposure of operating room personnel to non-coherent optical radiation by measuring the emission of blue light generated by operating lights. The values we obtained were largely below the exposure limit value of 100 W x m(-2) x sr(-1) provided by Legislative Decree no. 81/08 and European Directive 2006/25/EC, showing how workers can be exposed for longer than 8 hours without risk of acute health effects, confirming what was already said in literature. This work demonstrates, therefore, that the risk of acute nature of photochemical retinal damage, caused by exposure to blue light, is absent, if not exceeded the exposure limit values, on the basis of the current knowledge, however, respect for exposure level cannot protect against a possible retinal damage from chronic exposure, related to the total dose accumulated by the worker in the long-term.

[Occupational exposure to sevoflurane in pediatric operating rooms: the multi-point sampling method for risk assessment]. / Esposizione professionale al sevoflurano nelle sale operatorie di pertinenza pediatrica: il contributo del monitoraggio ambientale con tecnica multi-punto nella valutazione del rischio.

Several studies have shown that occupational exposure to anesthetic gases might be higher during pediatric surgery, probably due to the increased use of inhalational induction techniques. Our study aims to assess the level of exposure to sevoflurane in two rooms of pediatric surgery, using multi-point sampling method for environmental monitoring. The gas concentrations as well as its dispersion were measured in strategic points in the rooms for a total of 44 surgical interventions. Although the average of these concentrations has been rather low (1.32, SD +/- 1:55 ppm), the results obtained have documented a significant distribution kinetics difference inside the rooms as function of multiple factors among which there were the anesthetic technique used and the team involved. Therefore the method described allows to correctly analyze the spread of anesthetic gases and suggests a different risk stratification which may be dependent on the professional work.

Cross activity of orthologous WRKY transcription factors in wheat and Arabidopsis.

WRKY proteins are transcription factors involved in many plant processes including plant responses to pathogens. Here, the cross activity of TaWRKY78 from the monocot wheat and AtWRKY20 from the dicot Arabidopsis on the cognate promoters of the orthologous PR4-type genes wPR4e and AtHEL of wheat and Arabidopsis, respectively, was investigated. In vitro analysis showed the ability of TaWRKY78 to bind a -17/+80 region of the wPR4e promoter, containing one cis-acting W-box. Moreover, transient expression analysis performed on both TaWRKY78 and AtWRKY20 showed their ability to recognize the cognate cis-acting elements present in the wPR4e and AtHEL promoters, respectively. Finally, this paper provides evidence that both transcription factors are able to cross-regulate the orthologous PR4 genes with an efficiency slightly lower than that exerted on the cognate promoters. The observation that orthologous genes are subjected to similar transcriptional control by orthologous transcription factors demonstrates that the terminal stages of signal transduction pathways leading to defence are conserved and suggests a fundamental role of PR4 genes in plant defence. Moreover, these results corroborate the hypothesis that gene orthology imply similar gene function and that diversification between monocot and dicot has most likely occurred after the specialization of WRKY function.

Electrostimulation of hyperthermophile Thermotoga neapolitana cultures.

Hyperthermophile bioelectrochemical systems are seldom investigated although their superior control of microbial consortium and thermodynamic advantages. Hyperthermophilic Thermotogales, for instance, are able to produce hydrogen and lactic acid from wastes better than mesophilic bacteria. Here, the electrostimulation of Thermotoga neapolitana in single-chamber electrochemical bioreactors is studied. The glucose fermentation under CO2 pressure, as model metabolism, was tested at 80 °C. Results show that a dynamic polarization (±0.8 to ±1.2 V) drives glucose fermentation and biofilm stasis on electrodes. Under this condition, production of lactic acid (33 vs 12 mM) and yields of acetate and hydrogen (with lactic/acetic acid ratio of 1.18) were higher than those achieved with static polarization or open-circuit. Dynamic polarization is possibly exploitable to stimulate T. neapolitana in a hyperthermophile electrochemical system for various applications including control of power-to-gas processes or production of value-added products (hydrogen and lactic acid) from sugary wastes.

COVID-19 infection in cancer patients: what has been the contribution of Associazione Italiana Oncologia Medica (AIOM) to oncological care since the beginning of the first pandemic wave?

High mortality rates in elderly patients or in those with underlying chronic illnesses and/or a compromised immune system is a peculiar feature of COVID-19 infection. The possible coexistence of a cancer and COVID-19 infection in the same individual prompted concerns regarding their synergistic effect on prognosis. In order to balance patients' needs with the risks related to the infection, the question oncologists have asked from the beginning of the first wave of the pandemic has been: 'how can we deal with COVID-19 infection in cancer patients?' In pursuing its mission, the Associazione Italiana Oncologia Medica (AIOM) has made every possible effort to support cancer patients, health care professionals and institutions in the decision-making processes the pandemic has engendered within this scenario. The relevant documents as well as the educational and institutional initiatives the AIOM has taken are reported in this article.

Persistent ex vivo low number and functional in vitro recovery of circulating gammadelta T cells after removal of a cutaneous primary melanoma.

We recently described gammadelta T cells alterations in patients with a cutaneous primary melanoma. To evaluate whether gammadelta T cells alterations persisted after melanoma removal, we performed a follow-up study comparing the number and function of gammadelta T lymphocytes from 19 subjects, 4 years after the removal of a cutaneous primary melanoma, with the data obtained in the same subjects before the surgical intervention and with control donors. The number of circulating gammadelta(+) T cells after melanoma removal was not recovered to the levels found in controls. gammadelta(+) T cells producing TNF-alpha or IFN-gamma were increased after melanoma removal in comparison with the same subjects before surgical intervention or with control donors. After in vitro culture, both the percentage and the expansion of gammadelta T cells were recovered to the values found in controls. In conclusion, the functional capacity of gammadelta T cells was in vitro recovered after melanoma removal, whereas their ex vivo number remained at lower levels than control donors.

Modelling approach to obtain regional respiratory mechanics using electrical impedance tomography and volume-dependent elastance model.

OBJECTIVE: This paper presents a method for breath-by-breath estimation of regional respiratory mechanics without the need for special manoeuvres (such as inspiratory pause or low-flow inflation) using electrical impedance tomography (EIT) associated with pressure/airflow waveforms. APPROACH: We developed a method to estimate regional parameters using the regional impedance fraction, by multiplying it by global flow and volume waveforms. A volume-dependent elastance model was used to obtain compliance, resistance, volume-independent (E 1), and volume-dependent (E 2) components. Three swine under invasive mechanical ventilation were used to assess internal consistency and illustrate potential applications of our method. One animal (case 1) was ventilated with a broad range of tidal volumes to compare the consistency between regional and global resistances and compliances. Two other animals (cases 2 and 3) had respiratory compliance decreased, respectively, by overdistension and collapse as quantified by x-ray computed tomography. MAIN RESULTS: In case 1, derived global estimates obtained from the independent regional estimates were strongly associated with direct measurements of global mechanics (correlation coefficients of 0.9976 and 0.9981 for compliances and resistances, respectively), suggesting consistency of our modelling. In cases 2 and 3, the development of lung overdistension and collapse over time was captured by regional estimates. CONCLUSIONS: Using EIT and pressure/airflow waveforms, regional respiratory parameters can be obtained cycle-by-cycle, refining lung function monitoring. SIGNIFICANCE: The method allows real-time monitoring of regional parameters and their trends over time, which might be helpful to differentiate deterioration in lung compliance due to overdistension or collapse.

Defective levels of both circulating dendritic cells and T-regulatory cells correlate with risk of recurrence in cutaneous melanoma.

BACKGROUND: Immune markers in the peripheral blood of melanoma patients provide useful information for clinical management although there is poor consensus on circulating cells which could putatively reflect the disease activity and play a prognostic role. Here, we investigated both dendritic cells (DCs) and T-regulatory cells (Tregs). METHODS: The number of DC subsets as myeloid (m) and plasmacytoid was measured by flowcytometry in 113 melanoma patients in different clinical stages and correlated with the disease activity to evaluate the recurrence free survival (RFS) calculated as difference between baseline and post-surgical values in relation to the criteria for the melanoma staging, as primary tumor removal, sentinel lymph node biopsy and completion of lymph node dissection. RESULTS: Circulating mDC levels were significantly lower in metastatic melanoma than in other stages and inversely correlated to Treg values while both populations were similarly expressed in inactive disease at stage I-III. Furthermore, the levels of these cells after melanoma removal were apparently related to the disease activity since their persistent defect reflected high risk of recurrence and reduced the RFS. CONCLUSIONS: This work highlighted the role of immune cell measurement for the management of melanoma activity and the identification of patients at potential risk of recurrence based on the mDC ratio.

Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases.

Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times. Urinary concentration N-telopeptide of type-I collagen (NTX) and deoxypyridinolines, and serum C-telopeptide of type-I collagen (CTX), bone alkaline phosphatase (ALP), osteocalcin and Parathyroid hormone (PTH) was measured in the morning at baseline and after 4, 7, 14, 28, 56 and 84 days. Urinary ZA concentration was also measured. Zoledronic acid caused significant decreases of NTX and CTX (P<0.001), without any difference in percent changes between night and morning arms. Bone ALP and osteocalcin were also significantly affected by ZA (P=0.001), without any difference between arms. Parathyroid hormone significantly increased in both the arms; PTH increase was lower in the night arm (P=0.001). From the second administration onwards, urinary ZA level was significantly higher in the night arm (P<0.01). Administration of ZA at two opposite phases of the circadian cycle causes similar changes of bone-turnover marker levels, but has differential effects on the level of serum PTH.