Significance of Duodenal Prolactin Receptor Modulation by Calcium and Vitamin D in Sulpiride-Induced Hyperprolactinemia.

Background and Objectives: Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This study investigates whether calcium and vitamin D supplementation affects prolactin receptor (Prlr) gene expression in the duodenum, vertebrae, and kidneys of female rats with sulpiride-induced hyperprolactinemia. Materials and Methods: Twenty-one-week-old female Wistar rats were assigned to three groups: Group S consisted of ten rats who received sulpiride injections (10 mg/kg) twice daily for 6 weeks; Group D (10 rats) received daily supplementation of 50 mg calcium and 500 IU vitamin D along with sulpiride for the last 3 weeks; and Group C consisting of seven age-matched nulliparous rats serving as a control group. Real-time PCR was used to assess Prlr gene expression in the duodenum, vertebrae, and kidneys. Results: In Group S, Prlr gene expression was notably decreased in the duodenum (p < 0.01) but elevated in the vertebrae and kidneys compared to Group C. Conversely, Group D exhibited significantly increased Prlr expression in the duodenum (p < 0.01) alongside elevated expression in the vertebrae and kidneys. Conclusions: In sulpiride-induced hyperprolactinemia, decreased Prlr gene expression in the duodenum may lead to reduced intestinal calcium absorption. Consequently, prolactin may draw calcium from the skeletal system to maintain calcium balance, facilitated by increased Prlr gene expression in the vertebrae. However, vitamin D supplementation in sulpiride-induced hyperprolactinemia notably enhances Prlr gene expression in the duodenum, potentially ameliorating intestinal calcium absorption and mitigating adverse effects on bone health.

Effects of Autoclave Sterilization on Cyclic Fatigue Resistance in 5 Types of Rotary Endodontic Instruments: An In Vitro Study.

BACKGROUND Rotary endodontic instruments are increasingly used in root canal treatment and have replaced stainless steel manual files. Cyclic fatigue is the cyclic loading of stress to produce deformation or fracture. This study aimed to evaluate and compare the effects of autoclave sterilization on cyclic fatigue in 5 types of rotary endodontic instruments. MATERIAL AND METHODS ProTaper Universal, BioRace, ProTaper Next, Twisted File, and HyFlex CM instruments were included in this study. Each type included 96 instruments, divided into 4 groups according to the number of sterilization cycles (0, 1, 3, 5). After sterilization, each group of instruments was divided into 2 subgroups and tested for cyclic fatigue in 2 simulated canals (45 degrees both and 2 radii, 2 mm and 5 mm). The number of cycles to failure (NCF) was calculated, and statistical analyses were carried out using the t test, Mann-Whitney U test, and ANOVA, followed by the Tukey post hoc test (p<0.05). Fracture surfaces were analyzed using scanning electron microscopy (SEM). RESULTS Within the group of non-sterilized instruments, ProTaper Universal showed significantly lower resistance to cyclic fatigue compared to the other types of instruments (p<0.001). After repeated sterilization, a significantly higher mean of NCF was observed for BioRace (p<0.001), ProTaper Next (p<0.001), Twisted File (p<0.001), and HyFlex CM (p<0.001) compared to ProTaper Universal. The resistance of HyFlex CM was significantly higher compared to the other types of instruments (p<0.001). CONCLUSIONS The findings from this study showed that autoclave sterilization of newer rotary endodontic instruments could increase resistance to cyclic fatigue.

Determining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Questionnaire-Based Study.

BACKGROUND Emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) could lead to an increase in dental anxiety, avoidance of dental visits, and general neglect of oral health. This online questionnaire-based study conducted in April and May of 2021 in Serbia aimed to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on dental care. MATERIAL AND METHODS The study included 2060 adult citizens of the Republic of Serbia who participated in an anonymous online questionnaire based on a 5-point Likert scale. Data were collected on dental care routine prior to and during the pandemic, and the fear of negative consequences for oral health. The results were statistically analyzed using descriptive statistics, Pearson's correlation coefficient, ANOVA, and the paired t test. RESULTS Approximately one-fifth of the respondents postponed dental visits during the pandemic. Concern about postponing dental treatment was expressed by more than one-half of the respondents (57.1%), while 21.4% thought that they were already experiencing the consequences. Avoidance of preventive examinations and improvement of oral hygiene are more common among the elderly compared to younger respondents (P=.000). CONCLUSIONS The COVID-19 pandemic did not significantly affect the habit of avoiding dental interventions due to fear, but it did lead to part of the population completely avoiding even urgent dental interventions during the peak of the pandemic, and opting for tooth extraction rather than treatment. The strongest impact on dental care in the pandemic was among people over 64 years old.

COVID-19: Another Cause of Dental Anxiety?

BACKGROUND Fear has always been closely linked to dentistry but it could be intensified by the objective risks imposed by the pandemic. The objective of this study was to determine the profile of the frightened dental patient during the COVID-19 pandemic and determine measures taken by dentists to reduce fear and increase security among their patients. MATERIAL AND METHODS An anonymous online survey was conducted between March 15 and April 15, 2021. The respondents were 2060 adult citizens of the Republic of Serbia. In addition to demographic data, data related to the COVID-19 pandemic, dental fear, and attitudes and fear of dental interventions during the ongoing pandemic were compiled. The data were analyzed using descriptive statistics: the chi-square test and Pearson's coefficient. RESULTS Seventy percent of the respondents felt some level of fear of the ongoing pandemic, 50% felt fear of going to a dentist during the pandemic, 20% considered a dental office a hotspot for the transmission of SARS-CoV-2, and 43% would visit their dentist only in the case of emergency. CONCLUSIONS The COVID-19 pandemic has affected the attitudes and behavior of people pertaining to visits to dental offices. Identifying frightened patients and their opinions and fears at this challenging time would make it easier for dentists to include protocols in their everyday practice to increase a sense of security among their patients, such as implementing preventive measures in front of the patients, ensuring an empty waiting room, and providing telephone consultations.

Macrophages' contribution to ectopic osteogenesis in combination with blood clot and bone substitute: possibility for application in bone regeneration strategies.

PURPOSE: Given the great potential of macrophages in the processes of tissue repair and regeneration, the aim of our study was to examine the contribution that macrophages will have in osteogenic process when combined and implanted with blood clot (BC) and mineral bone substitute (MBS) in mice subcutaneous implantation model. METHODS: Three types of implants were constructed and implanted subcutaneously into BALB/c mice: (1) RMBM implants (made of resident tissue macrophages, BC and MBS), (2) BM implants (made of BC and MBS), and (3) M implants (made of MBS only) where the last two served as control implants. One, two, four and eight weeks after implantation implants were explanted, and histochemical, immunohistochemical, and histomorphometric analyses were performed. RESULTS: Increased vascularization, particularly pronounced two and four weeks after implantation and pronounced tissue infiltration in eight week term in RMBM implants compared with both other types, likewise the presence of osteoblast-like cells, osteoid-like structures, and more prominent osteopontin and osteocalcin immunoexpression in RMBM implants indicated more pronounced osteogenic process within them. CONCLUSION: Our results suggest that macrophages deserve to be considered as a cell component when constructing implants in bone regenerative medicine strategies to improve bone fracture healing process.

Predictors of Empathic Compassion: Do Spirituality, Religion, and Calling Matter?

OBJECTIVE: To determine whether physician spirituality, religion, and sense of calling toward medicine are predictors of self-reported empathic compassion. METHODS: We sampled 2000 practicing US physicians from all specialties and used self-reported measures of general and clinical empathic compassion taken from previous studies. Independent variables were single-item measures of calling, spirituality, and religiosity (importance of religion). RESULTS: The survey response rate was 64.5% (1289/2000). Physicians with a strong sense of calling were more likely to report higher general empathic compassion (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.26-3.15) and higher clinical empathic compassion (OR 3.33, 95% CI 2.07-5.36). Similarly, physicians who considered themselves spiritual were more likely to report higher general empathic compassion (OR 2.76, 95% CI 1.69-4.50) and higher clinical empathic compassion (OR 2.32, 95% CI 1.38-3.90). We did not find an association between religiosity and measures of physicians' empathic compassion. CONCLUSIONS: This national study of practicing US physicians from various specialties found that spirituality (not religiousness) and the identification of medicine as a calling are associated with physicians' empathic compassion. Further study is needed to understand how spirituality and calling are linked to prosocial behaviors among physicians that may be enhancing their clinical empathy and promoting compassionate patient care.

The mental health continuum-short form: The structure and application for cross-cultural studies-A 38 nation study.

OBJECTIVE: The Mental Health Continuum-Short Form (MHC-SF) is a brief scale measuring positive human functioning. The study aimed to examine the factor structure and to explore the cross-cultural utility of the MHC-SF using bifactor models and exploratory structural equation modelling. METHOD: Using multigroup confirmatory analysis (MGCFA) we examined the measurement invariance of the MHC-SF in 38 countries (university students, N = 8,066; 61.73% women, mean age 21.55 years). RESULTS: MGCFA supported the cross-cultural replicability of a bifactor structure and a metric level of invariance between student samples. The average proportion of variance explained by the general factor was high (ECV = .66), suggesting that the three aspects of mental health (emotional, social, and psychological well-being) can be treated as a single dimension of well-being. CONCLUSION: The metric level of invariance offers the possibility of comparing correlates and predictors of positive mental functioning across countries; however, the comparison of the levels of mental health across countries is not possible due to lack of scalar invariance. Our study has preliminary character and could serve as an initial assessment of the structure of the MHC-SF across different cultural settings. Further studies on general populations are required for extending our findings.

Prevalence of Human Cytomegalovirus and Epstein-Barr Virus in Chronic Periapical Lesions.

OBJECTIVE: The aim of this study was to investigate the presence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the tissue of chronic periapical lesions, and to compare the results in relation to the symptoms of patients and the size of the lesion. METHODS: Periapical lesions analyzed in the study were collected from the roots of the teeth indicated for extraction. Samples were divided according to the symptoms into groups of symptomatic and asymptomatic, and according the size into groups of small and large lesions. Polymerase chain reaction was used to detect HCMV and EBV. The amplification was performed in a DNA Thermal Cycler (Hybaid). RESULTS: Symptomatic lesions were 7.68 times more likely to be infected with HCMV than asymptomatic lesions (p < 0.001). Large symptomatic lesions were 73.50 times more likely to harbor HCMV than small symptomatic lesions (p < 0.001). Large symptomatic lesions were 7.64 times more likely to be infected with EBV than small symptomatic lesions (p = 0.05). Large symptomatic lesions were 5.38 times more likely to harbor dual HCMV/EBV infection than small symptomatic lesions (p = 0.115). CONCLUSION: Detection of HCMV and EBV in the samples of periapical lesions suggests an important role of herpesviruses in periapical tissue destruction.

Osteogenic potential of in vitro osteo-induced adipose-derived mesenchymal stem cells combined with platelet-rich plasma in an ectopic model.

PURPOSE: The osteogenic potential of in vitro osteo-induced adipose-derived mesenchymal stem cells (ADSCs) combined with platelet-rich plasma (PRP) and implanted on bone mineral matrix (BMM) carrier was examined in a subcutaneous model in Balb/c mice. METHODS: In vitro osteogenic differentiation of ADSCs was monitored by relative bone-related gene expression and osteocalcin expression at the third, seventh and 15th day. Test implants consisting of in vitro osteo-induced ADSCs, PRP and BMM (OPC implants) and control implants consisting of PRP and BMM (PC implants) were examined. The relative expression of the bone-related genes encoding osterix, osteocalcin, collagen type I α1 and alkaline phosphatase was examined in implants extracted at one, two, four and eight weeks. Histochemical, immunohistochemical and histomorphometric analyses of implants extracted at two and eight weeks were performed. RESULTS: The highest relative expression of bone-related genes and osteocalcin expression was found at the 15th day of in vitro osteogenic induction of the ADSCs. Permanent and continuous increased expression of bone-related genes was noticed in OPC implants at eight weeks. Expression peaks of bone-related genes in PC implants were at two and four weeks, but they significantly decreased at eight weeks. The signs of resorption, formation of callus-like tissue positive for osteocalcin and increased presence of bone cells were found in OPC implants compared with PC implants. A higher percentage of infiltrated tissue and vascularisation was found in OPC than in PC implants. CONCLUSIONS: The combination of in vitro osteo-induced ADSCs and PRP on BMM carrier represents a promising approach for bone regeneration.

Release behaviour of carbamazepine-loaded poly(ε-caprolactone)/poly(ethylene oxide) microspheres.

Poly(ε-caprolactone) (PCL), a biodegradable and biocompatible aliphatic polyester has a great potential as a drug carrying material in controlled drug delivery/release systems. The most simple and economical way to tailor the release profile of active substances from biodegradable polymer matrix is by the addition of the second polymeric component in the polymer matrix, i.e. by blending. This study describes the preparation and characterization of a carbamazepine-loaded microspheres by the use of PCL blended with poly(ethylene oxide) as a drug carrying material. By the use of two-component hydrophilic/hydrophobic polymer blend as a microspheres' matrix material, release profile of the drug can be modified and dictated. The microspheres prepared by classical oil-in-water emulsion solvent evaporation technique were characterized with respect to particle size and morphology, polymer matrix composition, encapsulation efficiency, physical state of the drug and in vitro release behaviour. It was presented that the release profile can be modified by the presence and the amount of hydrophilic component in the starting formulation of microspheres.

In vitro effect of beer, red and white wine on the morphology and surface roughness of human enamel.

BACKGROUND: Beer, red and white wine are acidic drinks whose frequent consumption can increase the risk of dental erosion. OBJECTIVES: To establish the effect of beer, red and white wine on the morphology and surface roughness (SR) of human enamel using different exposure times in a cyclic deand remineralization model in vitro. MATERIAL AND METHODS: The experiment included 33 surgically extracted impacted human third molars from patients aged 18-25 years. Enamel samples obtained by cutting crowns (n = 132) were submitted to alternate cycles of demineralization in (1) beer, (2) red wine, (3) white wine, (PC) positive control (orange juice), and remineralization in artificial saliva, which also represented a medium for negative control (NC). The experiment included cycles with different exposure times in alcoholic beverages and orange juice of 15, 30 and 60 min. Thus, 12 groups were formed (for each drink and each exposure time) containing 10 samples each, while the NC group consisted of 12 samples. Experiments were repeated 3x/day for 10 days. Enamel surface alterations were determined by stylus profilometry (average surface roughness (Ra)) and scanning electron microscopy (SEM). The Shapiro-Wilk test, independent samples Kruskal-Wallis test and multiple comparisons (all pairwise) were performed. RESULTS: With increasing exposure time, there was a positive correlation with Ra for white wineand orange juice-immersed samples (60 min compared to 15 min), which was also observed using SEM. There was no significant difference in the Ra between the other experimental samples for the same exposure time. CONCLUSIONS: This study confirms a certain erosive potential of beer, red and white wine, and a significant relationship with pH, titratable acidity (TA) and SR, but not with the exposure time for all tested alcoholic beverages. Moreover, differences among the ultrastructural patterns caused by alcoholic beverages over the enamel surface were observed.

Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35.

The acid-base equilibria of six ACE inhibitors (ACEIs), captopril, cilazapril, enalapril, lisinopril, quinapril, and ramipril, were investigated in the presence of micelles of nonionic surfactant Brij 35. The pKa values were potentiometrically determined at 25 °C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated in the computer program Hyperquad. On the basis of the shift in the pKa values (ΔpKa) determined in micellar media in relation to the pKa values previously determined in "pure" water, the effect of Brij 35 micelles on ACEIs ionization was estimated. The presence of nonionic Brij 35 micelles caused a shift in the pKa values of all ionizable groups of the investigated ACEIs (ΔpKa from - 3.44 to + 1.9) while shifting the protolytic equilibria of both acidic and basic groups toward the molecular form. The Brij 35 micelles expressed the most pronounced effect on the ionization of captopril among the investigated ACEIs and stronger effect on the ionization of amino than on the ionization of carboxyl groups. The obtained results suggest that ionizable functional groups of ACEIs are involved in interactions with palisade layer of nonionic Brij 35 micelles, which potentially can be considered in physiological conditions. Distribution diagrams of the investigated ACEIs equilibrium forms as a function of pH indicate that the change in distribution is most strongly expressed in pH range 4-8, which includes biopharmaceutically important pH values.

Ultrastructural changes in the cemento-enamel junction after vital tooth bleaching with fluoride and fluoride-free agents - a pilot study.

BACKGROUND: The impact of bleaching on the cemento-enamel junction (CEJ) is not well known. Due to frequent sensitivity of the cervical region of teeth after the vital bleaching, the aim of the present study was to evaluate the morphological features of the CEJ of human teeth after application of fluoridated and fluoride-free bleaching agents, as well as post-bleaching fluoridation treatment, by scanning electron microscopy (SEM) analysis. MATERIAL/METHODS: Thirty-five extracted permanent human teeth were longitudinally cut, yielding 70 specimens. Thirty specimens were randomly divided into the 3 experimental groups, and 20 specimens, were used as (2) control groups, each: negative (untreated) control group; positive control group treated with 35% hydrogen peroxide; experimental group 1, bleaching with 10% carbamide peroxide (CP); experimental group 2, treatment with a mixture of 10% CP and fluoride; and experimental group 3, treatment with 10% CP and 2% sodium fluoride gel applied 30 minutes after bleaching. Experimental groups were treated 8 h per day for 14 days. The samples were examined by SEM. RESULTS: The bleaching materials tested caused morphological changes to the surface of the CEJ. There was a statistically significant difference between experimental groups (Kruskal Wallis Test chi-square=11,668; p<0.005). Mean value of experimental group 2 scores showed statistically significant difference from groups 1 and 3. CONCLUSIONS: Bleaching gel with fluorides does not significantly change morphological appearance of the CEJ and represents a better choice than the hard tissue fluoridation process after bleaching.

The Effect of Glycol Derivatives on the Properties of Bio-Based Unsaturated Polyesters.

The scope of the present study was to prepare fully bio-based unsaturated polyester resins (UPRs) with comparable properties to the commercial formulations. The focus was set on the determination of the optimal prepolymer formulation using the same set of diacids (itaconic and succinic acid) and different diols (propylene glycol, isosorbide and neopentyl glycol) or its equimolar mixtures, keeping the fixed molar ratio of 1:1:2.1 in all feed compositions. Instead of commonly used styrene, bio-based dimethyl itaconate was used as a reactive diluent (RD). The rheology of the obtained resins was studied in detail. The effect of the used diol on structural (FTIR), thermal (DSC), thermomechanical (DMA), and mechanical (tensile) properties was explained. The properties of UPRs were found to be highly dependent on the diol used in the prepolymer formulation. The UPR with an equimolar ratio of propylene glycol and neopentyl glycol was shown to be the most promising candidate to compete with the commercial petroleum-based resins.

The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches.

The drug-human serum albumin binding interaction was evaluated on a stationary phase immobilized with human serum albumin using a mixture of phosphate buffer (pH 7.0) and acetonitrile modifier as mobile phase. The 33 compounds that have a wide structural and therapeutic diversity were analyzed by performing a large number of experiments. The interaction mechanism was interpreted based on: i) retention characteristics of structurally related compounds, ii) retention modeling, iii) quantitative structure retention relationship (QSRR), and iv) molecular docking. Small structural differences of related compounds (e.g., reflected in different lipophilicity and polarity) have been found to affect their different binding to human serum albumin. It was found that drug retention in HSA column can be successfully described by using the quadratic function. The isocratic (logk(14%)) and extrapolated (b0(LSS)) retention factors showed the highest correlation (r > 0.76) with the constant that defines the binding affinity for human serum albumin (ACD/I-Lab). Therefore, selected chromatographic parameters can demonstrate reliable applicability for rapid screening of drug-plasma protein binding in drug discovery. In QSRR study, the resulting SVM/logk(14%) and MLR/b0(LSS) models display high internal and external predictive power. The constitutional properties (double bonds, aromatic rings, benzyl, allyl, -amino and -sulfur containing functional groups) supported by the charged parts of surface area had a significant impact on human serum albumin-binding affinity, which was also confirmed with molecular docking study. The high structural diversity of the data set provides wide applicability of tested chromatographic conditions and constructed models for defining the pharmacokinetic profile and possible structural modifications that can increase plasma protein binding of newly synthesized, pharmaceutically important compounds.

Vascularization and osteogenesis in ectopically implanted bone tissue-engineered constructs with endothelial and osteogenic differentiated adipose-derived stem cells.

BACKGROUND: A major problem in the healing of bone defects is insufficient or absent blood supply within the defect. To overcome this challenging problem, a plethora of approaches within bone tissue engineering have been developed recently. Bearing in mind that the interplay of various diffusible factors released by endothelial cells (ECs) and osteoblasts (OBs) have a pivotal role in bone growth and regeneration and that adjacent ECs and OBs also communicate directly through gap junctions, we set the focus on the simultaneous application of these cell types together with platelet-rich plasma (PRP) as a growth factor reservoir within ectopic bone tissue engineering constructs. AIM: To vascularize and examine osteogenesis in bone tissue engineering constructs enriched with PRP and adipose-derived stem cells (ASCs) induced into ECs and OBs. METHODS: ASCs isolated from adipose tissue, induced in vitro into ECs, OBs or just expanded were used for implant construction as followed: BPEO, endothelial and osteogenic differentiated ASCs with PRP and bone mineral matrix; BPUI, uninduced ASCs with PRP and bone mineral matrix; BC (control), only bone mineral matrix. At 1, 2, 4 and 8 wk after subcutaneous implantation in mice, implants were extracted and endothelial-related and bone-related gene expression were analyzed, while histological analyses were performed after 2 and 8 wk. RESULTS: The percentage of vascularization was significantly higher in BC compared to BPUI and BPEO constructs 2 and 8 wk after implantation. BC had the lowest endothelial-related gene expression, weaker osteocalcin immunoexpression and Spp1 expression compared to BPUI and BPEO. Endothelial-related gene expression and osteocalcin immunoexpression were higher in BPUI compared to BC and BPEO. BPEO had a higher percentage of vascularization compared to BPUI and the highest CD31 immunoexpression among examined constructs. Except Vwf, endothelial-related gene expression in BPEO had a later onset and was upregulated and well-balanced during in vivo incubation that induced late onset of Spp1 expression and pronounced osteocalcin immunoexpression at 2 and 8 wk. Tissue regression was noticed in BPEO constructs after 8 wk. CONCLUSION: Ectopically implanted BPEO constructs had a favorable impact on vascularization and osteogenesis, but tissue regression imposed the need for discovering a more optimal EC/OB ratio prior to considerations for clinical applications.

Ultrastructural changes in the cemento-enamel junction caused by acidic beverages: An in vitro study.

The present in vitro study was aimed at evaluating the morphological changes in the cemento-enamel junction (CEJ) after exposure to acidic beverages using the scanning electron microscopy (SEM). The initial pH and titratable acidity (TA) was analyzed from follow groups: (I) Coca cola, (II) orange juice, (III) Cedevita, (IV) Red Bull, (V) Somersby cider, and (VI) white wine. The CEJ samples (n = 64), obtained from unerupted third molars, were allocated to one control (artificial saliva, n = 16) and six experimental groups (n = 8). The experimental samples were immersed in beverages (50 ml) for 15 min, three times daily, 10 days, and in artificial saliva between immersions. SEM analysis was performed in a blind manner, according to scoring scale. One-way ANOVA and Tukey's post hoc tests, as well as Kruskal-Wallis and Mann-Whitney U test used for statistical analysis. The pH values of the acidic beverages ranged from 2.65 (Coca cola) to 3.73 (orange juice), and TA ranged from 1.90 ml (Coca cola) to 5.70 ml (orange juice) of NaOH to reach pH 7.0. The SEM analysis indicated statistically significant differences between the control samples and those immersed in acidic beverages. The Groups IV, I, and II, showed the highest CEJ damage grade while those of the Group VI were the lowest. All the tested acidic beverages caused morphological changes in the CEJ with a smaller or larger exposure of dentine surface, and were not always related to the pH or TA of acidic beverages.

Micelle and vesicle formation of amphiphilic nanoparticles.

Nanoparticle brushes: Complex nanostructures can be formed by self assembly of amphiphilic CdSe/CdS core-shell nanoparticles that bear a brushlike layer of poly(ethylene oxide) chains. This route is based on controlling the volume fractions of hydrophilic and hydrophobic moieties within the particles and allows the formation of micellar, cylindrical, or vesicular nanoobjects (see picture).

Expression of prolactin receptors in the duodenum, kidneys and skeletal system during physiological and sulpiride-induced hyperprolactinaemia.

INTRODUCTION AND AIM: Hyperprolactinaemia in pregnancy leads to mild and reversible changes in the maternal skeletal system, and medicamentous hyperprolactinemia causes more detrimental effects. We conducted an experimental study to evaluate differences between Prlr gene expression in the duodenum, vertebrae and kidneys during physiological and medicamentous hyperprolactinaemia, which could influence calcium homeostasis. METHODS: Experimental animals (18 weeks old, Wistar female rats) were divided as follows: group P (nine rats that were 3 weeks pregnant), group M (ten rats that were intramuscularly administrated sulpiride (10 mg/kg) twice daily for 3 weeks), and the control group (C, ten age-matched nulliparous rats, 18-week-old). Laboratory investigations included measurements of serum ionized calcium, phosphorus, urinary calcium and phosphorus excretion, osteocalcin (OC), serum procollagen type 1 N-terminal propeptide (P1NP), vitamin D, parathyroid hormone (PTH) and prolactin (PRL). Relative quantification of gene expression for prolactin receptors in the duodenum, vertebrae and kidneys was determined using real-time PCR. RESULTS: Expression of the Prlr gene was significantly higher in the duodenum (p < 0.001) and lower in vertebrae (p < 0.001) and kidneys (p < 0.01) in rats with physiological hyperprolactinaemia (PHP) than in the control group. Significantly lower Prlr expression in the duodenum was verified (p < 0.001), along with increased Prlr gene expression in vertebrae (p < 0.001) and kidneys (p < 0.01), in rats with medicamentous hyperprolactinaemia (MHP) than in the C group. CONCLUSIONS: Downregulation of Prlr gene expression in the duodenum may explain the diminished intestinal calcium absorption in medicamentous hyperprolactinaemia. Prolactin takes calcium from the skeletal system following increased Prlr gene expression in the vertebrae to maintain calcium homeostasis, which increases the harmful effect on bone metabolism compared to that of physiological hyperprolactinaemia.

A perspective on multi-target drug discovery and design for complex diseases.

Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.