The pianosa contourite depositional system (northern Tyrrhenian sea): drift morphology and plio-quaternary stratigraphic evolution

The Pianosa Contourite Depositional System (CDS) is located in the Corsica Trough (Northern Tyrrhenian Sea), a confined basin dominated by mass transport and contour currents in the eastern flank and by turbidity currents in the western flank. The morphologic and stratigraphic characterisation of the Pianosa CDS is based on multibeam bathymetry, seismic reflection data (multi-channel high resolution mini GI gun, single-channel sparker and CHIRP), sediment cores and ADCP data. The Pianosa CDS is located at shallow to intermediate water depths (170 to 850 m water depth) and is formed under the influence of the Levantine Intermediate Water (LIW). It is 120 km long, has a maximum width of 10 km and is composed of different types of muddy sediment drifts: plastered drift, separated mounded drift, sigmoid drift and multicrested drift. The reduced tectonic activity in the Corsica Trough since the early Pliocene permits to recover a sedimentary record of the contourite depositional system that is only influenced by climate fluctuations. Contourites started to develop in the Middle-Late Pliocene, but their growth was enhanced since the Middle Pleistocene Transition (0.7���0.9 Ma). Although the general circulation of the LIW, flowing northwards in the Corsica Trough, remained active all along the history of the system, contourite drift formation changed, controlled by sediment influx and bottom current velocity. During periods of sea level fall, fast bottom currents often eroded the drift crest in the middle and upper slope. At that time the proximity of the coast to the shelf edge favoured the formation of bioclastic sand deposits winnowed by bottom currents. Higher sediment accumulation of mud in the drifts occurred during periods of fast bottom currents and high sediment availability (i.e. high activity of turbidity currents), coincident with periods of sea level low-stands. Condensed sections were formed during sea level high-stands, when bottom currents were more sluggish and the turbidite system was disconnected, resulting in a lower sediment influx.

What can exploratory modelling tell us about the ecobiology of European sea bass ( Dicentrarchus labrax ): a comprehensive overview

European sea bass, Dicentrarchus labrax, is a highly valuable species in Europe, both for aquaculture in the Mediterranean Sea and for commercial and recreational fisheries in the North East Atlantic Ocean. Subjected to increasing fishing pressure, the wild population has recently experienced significant recruitment fluctuation as well as a northward extension of its distribution area in the North Sea. While the nature of the ecological and/or physiological processes involved remains unresolved, ontogenetic habitat shifts and adult site fidelity could increase the species��� vulnerability to climate change and overfishing. As managers look for expert information to propose management scenarios leading to sustainable exploitation, exploratory modelling appears to be a cost-efficient approach to enhance the understanding of recruitment dynamics and the spatio-temporal scales over which fish populations function. A conceptual modelling framework and its specific data requirements are discussed to tackle some sound ecological questions regarding this species. We consequently provide an updated review of current knowledge on bass population structure, biology and ecology. This paper will hence be particularly valuable to develop spatially-explicit models of European sea bass dynamics under environmental and anthropogenic forcing. Knowledge gaps requiring further research efforts are also reported.

Otolith shape variation provides a marker of stock origin for north Atlantic bluefin tuna (Thunnus thynnus)

Two stocks of bluefin tuna (Thunnus thynnus) inhabit the north Atlantic; the western and eastern stocks spawn in the Gulf of Mexico and the Mediterranean Sea respectively. Trans-Atlantic movements occur outside spawning time whereas natal homing maintains stock structure. Commercial fisheries may exploit a mixed assemblage of both stocks. The incorporation of mixing rates into stock assessment is precluded by uncertainties surrounding stock discrimination. Otolith shape descriptors were used to characterise western and eastern stocks of Atlantic bluefin tuna in the present study and to estimate stock composition in catches of unknown origin. Otolith shape varied with length and between locations and years. Within a restricted size range (200-297-cm fork length (FL)) the two stocks were distinguished with an accuracy of 83%. Bayesian stock mixture analysis indicated that samples from the east Atlantic and Mediterranean were predominantly of eastern origin. The proportion assigned to the eastern stock showed slight spatial variation; however, overlapping 95% credible intervals indicated no significant difference (200-297 cm FL: central Atlantic, 73-100%; Straits of Gibraltar, 73-100%; Morocco, 50-99%; Portugal 64-100%). Otolith shape could be used in combination with other population markers to improve the accuracy of mixing rate estimates for Atlantic bluefin tuna.

Toxicity and Growth Assessments of Three Thermophilic Benthic Dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) Developing in the Southern Mediterranean Basin

armful benthic dinoflagellates, usually developing in tropical areas, are expanding to temperate ecosystems facing water warming. Reports on harmful benthic species are particularly scarce in the Southern Mediterranean Sea. For the first time, three thermophilic benthic dinoflagellates (Ostreopsis cf. ovata, Prorocentrum lima and Coolia monotis) were isolated from Bizerte Bay (Tunisia, Mediterranean) and monoclonal cultures established. The ribotyping confirmed the morphological identification of the three species. Maximum growth rates were 0.59 �� 0.08 d���1 for O. cf. ovata, 0.35 �� 0.01 d���1 for C. monotis and 0.33 �� 0.04 d���1 for P. lima. Toxin analyses revealed the presence of ovatoxin-a and ovatoxin-b in O. cf. ovata cells. Okadaic acid and dinophysistoxin-1 were detected in P. lima cultures. For C. monotis, a chromatographic peak at 5.6 min with a mass m/z = 1061.768 was observed, but did not correspond to a mono-sulfated analogue of the yessotoxin. A comparison of the toxicity and growth characteristics of these dinoflagellates, distributed worldwide, is proposed.

Connectivity patterns inferred from the genetic structure of white seabream (Diplodus sargus L.)

Themarine environment seems, at first sight, to be a homogeneousmediumlacking barriers to species dispersal. Nevertheless, populations of marine species show varying levels of gene flow and population differentiation, so barriers to gene flow can often be detected. Weaimto elucidate the role of oceanographical factors ingenerating connectivity among populations shaping the phylogeographical patterns in the marine realm, which is not only a topic of considerable interest for understanding the evolution ofmarine biodiversity but also formanagement and conservation of marine life. For this proposal,we investigate the genetic structure and connectivity between continental and insular populations ofwhite seabreamin North East Atlantic (NEA) and Mediterranean Sea (MS) aswell as the influence of historical and contemporary factors in this scenario using mitochondrial (cytochrome b) and nuclear (a set of 9 microsatellite) molecular markers. Azores population appeared genetically differentiated in a single cluster using Structure analysis. This result was corroborated by Principal Component Analysis (PCA) and Monmonier algorithm which suggested a boundary to gene flow, isolating this locality. Azorean population also shows the highest significant values of FST and genetic distances for both molecular markers (microsatellites and mtDNA). We suggest that the breakdown of effective genetic exchange between Azores and the others' samples could be explained simultaneously by hydrographic (deep water) and hydrodynamic (isolating current regimes) factors acting as barriers to the free dispersal of white seabream(adults and larvae) and by historical factors which could be favoured for the survival of Azorean white seabream population at the last glaciation. Mediterranean islands show similar genetic diversity to the neighbouring continental samples and nonsignificant genetic differences. Proximity to continental coasts and the current system could promote an optimal larval dispersion among Mediterranean islands (Mallorca and Castellamare) and coasts with high gene flow.

Posidonia oceanica (L.) Delile in its westernmost biogeographical limit (northwestern Alboran Sea): Meadows characterisation, phenology and flowering events

Posidonia oceanica is a Mediterranean endemic seagrass species that forms meadows covering ca. 2.5���4.5 millions of hectares, representing ca.25 % of the infralittoral and shallow circalittoral (down to 50m) bottoms of the Mediterranean. This seagrass is considered a habitat-engineer species and provides an elevated number of ecosystem services. In addition the Marine Strategy Framework Directive (MSFD, 2008/56/EC) includes seagrass like elements to evaluate the ���Good Environmental Status��� of the European coasts. Information about their phenological characteristic and structure of the meadows is needed for indicator estimations in order to establish their conservation status. The studied meadows are located in the westernmost limit of the P. oceanica distribution (North-western Alboran Sea) in the vecinity of the Strait of Gibraltar, an Atlantic-Mediterranean water transition area. Four sites were selected from East to West: Paraje Natural de Acantilados de Maro-Cerro Gordo (hereafter Maro), Special Area of Conservation ���Calahonda��� (hereafter Calahonda), Site of Community Importance Estepona (hereafter Estepona) and Punta Chullera (hereafter Chullera) where P. oceanica present their westernmost meadows. Phenological data were recorded from mid November to mid December in P. oceanica patches located at 2 ��� 3 m depth. At each site three types of patches (patch area <1m2, small patches; 1-2 m2, medium patches and >2 m2, large patches) were sampled. At each patch and site, 3 quadrants of 45 x 45 cm were sampled for shoot and inflorescences density measurements. In each quadrant, 10 random shoots were sampled for shoot morphology (shoot height and number of leaves). Shoot and inflorescences densities were standardized to squared meters. All the studied P. oceanica meadows develop on rocks and they present a fragmented structure with a coverage ranging between ca. 45% in Calahonda and Estepona and ca. 31% in Maro. The meadows of Chullera are reduced to a few small - medium patches with areas ranging between 0.5-1.5 m2 (Fig. 1). The meadows of Chullera and Estepona presented similar values of shoot density (ca. 752 ��� 662 shoots m-2, respectively) and leaf height (ca. 25 cm). Similarly, the Calahonda and Maro meadows also showed similar values of shoot density (ca. 510 ��� 550 shoots m-2, respectively) but displaying lower values than those of sites located closer to the Strait of Gibraltar. Regarding patch sizes and leaf height, the longest leaves (ca. 25 cm) were found in medium and large patches, but the number of leaves per shoot were higher in the small and the medium size patches (ca. 6.3 leaves per shoot). Flowering was only detected at the Calahonda meadows with maximum values of ca. 330 inflorescences m-2 (115.2 �� 98.2 inflorescences m-2, n= 9; mean �� SD) (Fig.1). Inflorescence density was not significant different among patches of different sizes. In the Alboran Sea and unlike the studied meadows, extensive beds of P. oceanica occur at the National Park of Cabo de Gata (northeastern Alboran Sea), but from east to west (Strait of Gibraltar), meadows are gradually fragmenting and their depth range decrease from 30m to 2m depth between Cabo de Gata and Chullera, respectively. Probably, the Atlantic influence and the characteristic oceanographic conditions of the Alboran Sea (i.e., higher turbidity, higher water turbulence) represent a developmental limiting factor for P. oceanica at higher depths. Similarities between the meadows located closer to Strait of Gibraltar (Chullera and Estepona) were detected as well as between those more distant (Calahonda and Maro). The first ones showed higher values of shoot densities and leaf heights than the formers, which could be relating to the higher hydrodynamic exposure found at Chullera and Estepona meadows. Regarding flowering events, sexual reproduction in P. oceanica is not common in different locations of the Mediterranean Sea. The available information seems to indicate that flowering represent an irregular event and it is related to high seawater temperature. In fact, the flowering episodes that occurred in Calahonda in November 2015, match with the warmest year ever recorded. This is the third flowering event registered in these meadows located close to the westernmost distributional limit of P. oceanica (M��laga, Alboran Sea), which could indicates that these meadows presents a healthy status. Furthermore, the absence of significant differences in relation to inflorescence density between patches of different sizes may be indicating that the fragmentation does not necessarily influence on the flowering of this seagrass species.

Tyrosine monitoring in children with early and continuously treated phenylketonuria: Results of an international practice survey

Investigations into the biochemical markers associated with executive function (EF) impairment in children with early and continuously treated phenylketonuria (ECT-PKU) remain largely phenylalanine-only focused, despite experimental data showing that a high phenylalanine:tyrosine (phe:tyr) ratio is more strongly associated with EF deficit than phe alone. A high phe:tyr ratio is hypothesized to lead to a reduction in dopamine synthesis within the brain, which in turn results in the development of EF impairment. This paper provides a snapshot of current practice in the monitoring and/or treatment of tyrosine levels in children with PKU, across 12 countries from Australasia, North America and Europe. Tyrosine monitoring in this population has increased over the last 5 years, with over 80% of clinics surveyed reporting routine monitoring of tyrosine levels in infancy alongside phe levels. Twenty-five percent of clinics surveyed reported actively treating/managing tyrosine levels (with supplemental tyrosine above that contained in PKU formulas) to ensure tyrosine levels remain within normal ranges. Anecdotally, supplemental tyrosine has been reported to ameliorate symptoms of both attention deficit hyperactivity disorder and depression in this population. EF assessment of children with ECT-PKU was likewise highly variable, with 50% of clinics surveyed reporting routine assessments of intellectual function. However when function was assessed, test instruments chosen tended towards global measures of IQ prior to school entry, rather than specific assessment of EF development. Further investigation of the role of tyrosine and its relationship with phe and EF development is needed to establish whether routine tyrosine monitoring and increased supplementation is recommended.

Relationships between appetite and quality of life in hemodialysis patients

The aim of this paper was to investigate the association between appetite and Kidney-Disease Specific Quality of Life in maintenance hemodialysis patients. Quality of Life (QoL) was measured using the Kidney Disease Quality Of Life survey. Appetite was measured using self-reported categories and a visual analog scale. Other nutritional parameters included Patient-Generated Subjective Global Assessment (PGSGA), dietary intake, body mass index and biochemical markers C-Reactive Protein and albumin. Even in this well nourished sample (n=62) of hemodialysis patients, PGSGA score (r=-0.629), subjective hunger sensations (r=0.420) and body mass index (r=-0.409) were all significantly associated with the Physical Health Domain of QoL. As self-reported appetite declined, QoL was significantly lower in nine domains which were mostly in the SF36 component and covered social functioning and physical domains. Appetite and other nutritional parameters were not as strongly associated with the Mental Health domain and Kidney Disease Component Summary Domains. Nutritional parameters, especially PGSGA score and appetite, appear to be important components of the physical health domain of QoL. As even small reductions in nutritional status were associated with significantly lower QoL scores, monitoring appetite and nutritional status is an important component of care for hemodialysis patients.

Is recovery driven by central or peripheral factors? A role for the brain in recovery following intermittent-sprint exercise

Prolonged intermittent-sprint exercise (i.e., team sports) induce disturbances in skeletal muscle structure and function that are associated with reduced contractile function, a cascade of inflammatory responses, perceptual soreness, and a delayed return to optimal physical performance. In this context, recovery from exercise-induced fatigue is traditionally treated from a peripheral viewpoint, with the regeneration of muscle physiology and other peripheral factors the target of recovery strategies. The direction of this research narrative on post-exercise recovery differs to the increasing emphasis on the complex interaction between both central and peripheral factors regulating exercise intensity during exercise performance. Given the role of the central nervous system (CNS) in motor-unit recruitment during exercise, it too may have an integral role in post-exercise recovery. Indeed, this hypothesis is indirectly supported by an apparent disconnect in time-course changes in physiological and biochemical markers resultant from exercise and the ensuing recovery of exercise performance. Equally, improvements in perceptual recovery, even withstanding the physiological state of recovery, may interact with both feed-forward/feed-back mechanisms to influence subsequent efforts. Considering the research interest afforded to recovery methodologies designed to hasten the return of homeostasis within the muscle, the limited focus on contributors to post-exercise recovery from CNS origins is somewhat surprising. Based on this context, the current review aims to outline the potential contributions of the brain to performance recovery after strenuous exercise.

Molecular profiling of exudate from chronic ulcerated wounds

Non-healing wounds represent a significant burden to healthcare systems and societies worldwide. Current best practice treatments of chronic wounds can require patients to undergo extensive periods of therapy without any positive outcome. This consumes substantial healthcare resources and severely impacts patient quality of life. At present, there are no measures to predict a patient's response to best practice care. The hypothesis of this thesis was that biochemical markers could be found within the wound fluid of chronic ulcers and these markers could predict the healing outcome of an ulcer undergoing best practice care. Discovery phase proteomic and mass spectrometry techniques were utilised to determine novel proteins that correlated with the healing outcome of ulcers. These candidate biomarkers could be developed into simple dip-stick tools for use in clinical practice. This would aid clinicians in the choice of effective wound management strategies to address hard-to-heal wounds.

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 �� 10���8) loci, some including known iron-related genes (���HFE, ���SLC40A1, ���TF, ���TFR2, ���TFRC, ���TMPRSS6) and others novel (���ABO, ���ARNTL, ���FADS2, ���NAT2, ���TEX14). SNPs at ���ARNTL, ���TF, and ���TFR2 affect iron markers in ���HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Placental abruption : Studies on incidence, risk factors and potential predictive biomarkers

Placental abruption, one of the most significant causes of perinatal mortality and maternal morbidity, occurs in 0.5-1% of pregnancies. Its etiology is unknown, but defective trophoblastic invasion of the spiral arteries and consequent poor vascularization may play a role. The aim of this study was to define the prepregnancy risk factors of placental abruption, to define the risk factors during the index pregnancy, and to describe the clinical presentation of placental abruption. We also wanted to find a biochemical marker for predicting placental abruption early in pregnancy. Among women delivering at the University Hospital of Helsinki in 1997-2001 (n=46,742), 198 women with placental abruption and 396 control women were identified. The overall incidence of placental abruption was 0.42%. The prepregnancy risk factors were smoking (OR 1.7; 95% CI 1.1, 2.7), uterine malformation (OR 8.1; 1.7, 40), previous cesarean section (OR 1.7; 1.1, 2.8), and history of placental abruption (OR 4.5; 1.1, 18). The risk factors during the index pregnancy were maternal (adjusted OR 1.8; 95% CI 1.1, 2.9) and paternal smoking (2.2; 1.3, 3.6), use of alcohol (2.2; 1.1, 4.4), placenta previa (5.7; 1.4, 23.1), preeclampsia (2.7; 1.3, 5.6) and chorioamnionitis (3.3; 1.0, 10.0). Vaginal bleeding (70%), abdominal pain (51%), bloody amniotic fluid (50%) and fetal heart rate abnormalities (69%) were the most common clinical manifestations of placental abruption. Retroplacental blood clot was seen by ultrasound in 15% of the cases. Neither bleeding nor pain was present in 19% of the cases. Overall, 59% went into preterm labor (OR 12.9; 95% CI 8.3, 19.8), and 91% were delivered by cesarean section (34.7; 20.0, 60.1). Of the newborns, 25% were growth restricted. The perinatal mortality rate was 9.2% (OR 10.1; 95% CI 3.4, 30.1). We then tested selected biochemical markers for prediction of placental abruption. The median of the maternal serum alpha-fetoprotein (MSAFP) multiples of median (MoM) (1.21) was significantly higher in the abruption group (n=57) than in the control group (n=108) (1.07) (p=0.004) at 15-16 gestational weeks. In multivariate analysis, elevated MSAFP remained as an independent risk factor for placental abruption, adjusting for parity ��� 3, smoking, previous placental abruption, preeclampsia, bleeding in II or III trimester, and placenta previa. MSAFP ��� 1.5 MoM had a sensitivity of 29% and a false positive rate of 10%. The levels of the maternal serum free beta human chorionic gonadotrophin MoM did not differ between the cases and the controls. None of the angiogenic factors (soluble endoglin, soluble fms-like tyrosine kinase 1, or placental growth factor) showed any difference between the cases (n=42) and the controls (n=50) in the second trimester. The levels of C-reactive protein (CRP) showed no difference between the cases (n=181) and the controls (n=261) (median 2.35 mg/l [interquartile range {IQR} 1.09-5.93] versus 2.28 mg/l [IQR 0.92-5.01], not significant) when tested in the first trimester (mean 10.4 gestational weeks). Chlamydia pneumoniae specific immunoglobulin G (IgG) and immunoglobulin A (IgA) as well as C. trachomatis specific IgG, IgA and chlamydial heat-shock protein 60 antibody rates were similar between the groups. In conclusion, although univariate analysis identified many prepregnancy risk factors for placental abruption, only smoking, uterine malformation, previous cesarean section and history of placental abruption remained significant by multivariate analysis. During the index pregnancy maternal alcohol consumption and smoking and smoking by the partner turned out to be the major independent risk factors for placental abruption. Smoking by both partners multiplied the risk. The liberal use of ultrasound examination contributed little to the management of women with placental abruption. Although second-trimester MSAFP levels were higher in women with subsequent placental abruption, clinical usefulness of this test is limited due to low sensitivity and high false positive rate. Similarly, angiogenic factors in early second trimester, or CRP levels, or chlamydial antibodies in the first trimester failed to predict placental abruption.

Substance misuse problems during pregnancy with special emphasis on buprenorphine

Maternal drug abuse during pregnancy endangers the future health and wellbeing of the infant and growing child. On the other hand, via maternal abstinence, these problems would never occur; so the problems would be totally preventable. Buprenorphine is widely used in opioid maintenance treatment as a substitute medication. In Finland, during 2000 s buprenorphine misuse has steadily increased. In 2009 almost one third of clientele of substance treatment units were in treatment because of buprenorphine dependence. At Helsinki Women s Clinic the first child with prenatal buprenorphine exposure was born in 2001. During 1992-2001 in the three capital area maternity hospitals (Women s clinic, Maternity hospital, Jorvi hospital) 524 women were followed at special antenatal clinics due to substance abuse problems. Three control women were drawn from birth register to each case woman and matched for parity and same place and date of the index birth. According to register data mortality rate was 38-fold higher among cases than controls within 6-15 years after index birth. Especially, the risk for violent or accidental death was increased. The women with substance misuse problems had also elevated risk for viral hepatitis and psychiatric morbidity. They were more often reimbursed for psychopharmaceuticals. Disability pensions and rehabilitation allowances were more often granted to cases than controls. In total 626 children were born from these pregnancies. According to register data 38% of these children were placed in out-of-home care as part of child protection services by the age of two years, and half of them by the age of 12 years, the median follow-up time was 5.8 years. The risk for out-of-home care was associated with factors identifiable during the pre- and perinatal period. In 2002-2005 67 pregnant women with buprenorphine dependence were followed up at the Helsinki University Hospital, Department of Obstetrics and Gynecology. Their pregnancies were uneventful. The prematurity rate was similar and there were no more major anomalies compared to the national statistics. The neonates were lighter compared to the national statistics. They were also born in good condition, with no perinatal hypoxia as defined by standard clinical parameters or certain biochemical markers in the cord blood: erythropoietin, S100 and cardiac troponin-t. Almost 80% of newborns developed neonatal abstinence syndrome (NAS) and two third of them needed morphine medication for it. Maternal smoking over ten cigarettes per day aggravated and benzodiazepine use attenuated NAS. An infant s highest urinary norbuprenorphine concentration during their first 3 days of life correlated with the duration of morphine treatment. The average length of infant s hospital stay was 25 days.

Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats

We conducted the present study to investigate the therapeutic effects of the antiresorptive agent zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF), in a rat model of postmenopausal osteoporosis. Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post surgery, rats were randomized into six groups: (1) sham + vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100 mu g/kg, i.v. single dose), (4) OVX + ZOL (50 mu g/kg, i.v. single dose), (5) OVX + ALF (0.5 mu g/kg, oral gauge daily) and (6) OVX + ZOL (50 mu g/kg, i.v. single dose) + ALF (0.5 mu g/kg, oral gauge daily) for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the combination treatment of ZOL and ALF was more effective than each administered as a monotherapy. Moreover, combination therapy using ZOL and ALF preserved the trabecular micro-architecture and cortical bone porosity. Furthermore, the combination treatment of ZOL and ALF corrected the decrease in serum calcium and increase in serum alkaline phosphatase and the tartarate-resistant acid phosphatase level better than single-drug therapy using ZOL or ALF in OVX rats. In addition, the combination treatment of ZOL and ALF corrected the increase in urine calcium, phosphorous and creatinine levels better than single-drug therapy using ZOL or ALF in OVX rats. These data suggest that the combination treatment of ZOL and ALF has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.

Development, in vitro and in vivo characterization of zoledronic acid functionalized hydroxyapatite nanoparticle based formulation for treatment of osteoporosis in animal model

We investigated the potential of using novel zoledronic acid (ZOL)-hydroxyapatite (HA) nanoparticle based drug formulation in a rat model of postmenopausal osteoporosis. By a classical adsorption method, nanoparticles of HA loaded with ZOL (HNLZ) drug formulation with a size range of 100-130 nm were prepared. 56 female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post surgery, rats were randomized into seven groups and treated with various doses of HNLZ (100, 50 and 25 mu g/kg, intravenous single dose), ZOL (100 mu g/kg, intravenous single dose) and HA nanoparticle (100 mu g/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. After three months treatment period, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for trabecular microarchitecture. Sensitive biochemical markers of bone formation and bone resorption in serum were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the therapy with HNLZ drug formulation was more effective than ZOL therapy in OVX rats. Moreover, HNLZ drug therapy preserved the trabecular microarchitecture better than ZOL therapy in OVX rats. Furthermore, the HNLZ drug formulation corrected increase in serum levels of bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, osteocalcin, tartrate-resistant acid phosphatase 5b and C-telopeptide of type 1 collagen better than ZOL therapy in OVX rats. The results strongly suggest that HNLZ novel drug formulation appears to be more effective approach for treating severe osteoporosis in humans. (C) 2014 Elsevier B.V. All rights reserved.