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Growth and reproductive performance traits are important economic indicators for analyzing the overall performance of breeding systems. This study aims to evaluate the comparative performance of two Algerian sheep (Rumbi and Hamra) in terms of growth and reproductive performance, and the effect of factors such as breed, season of birth, mode of birth and age of the mother on this performance in a semi-intensive breeding system. The reproductive performance of 577 Rumbi ewes and 1328 Hamra ewes bred at the Tiaret and Saïda experimental stations respectively, was analyzed using performance monitoring data. Fertility rates for the Rumbi and Hamra breeds of 87.14% and 78.8% respectively were practically similar (p > 0,05). Litter size at birth and weaning was significantly higher in the Hamra breed than in the Rumbi breed (p < 0,05). Weaning mortality was significantly higher in the Hamra breed than in the Rumbi breed, with an average of 22.60% versus 14.94% (p < 0,05). The effect of factors showed that there was a highly significant effect of the mother's age and season of birth on the reproductive performance of the Hamra and Rumbi breeds with a p < 0.0001 on fertility, litter size at birth, litter size at weaning and fertility. There was a significant effect of the year factor on reproductive performance with p = 0,013 for the Hamra breed and p = 0,031 for the Rumbi breed. The results of this study showed that Rumbi lambs were heavier at birth than Hamra lambs. The values observed were 4,86 kg versus 3,10 kg for the Hamra breed, with a highly significant difference (p < 0,0001), so that the average daily pre-weaning weight gains of Rumbi lambs were higher than those of Hamra lambs, at 0,195 kg/day versus 0,113 kg/day for Hamra lambs, with a high significance (p < 0,0001). The effect of factors showed that there was a significant effect of the mother's age on the ADGs (0-30), (30-70) and (70-90) of the Hamra and Rumbi breeds with a p = 0,034 and p = 0,02 respectively. There was also a highly significant effect of the birth mode effect on ADGs (0-30), (30-70) and (70-90) only for the Hamra breed with a p = 0,004. The effect of the birth weight on ADGs was not significant for both Hamra and Rumbi breeds with a p > 0,05. According to the findings of this study, the Hamra breed had superior reproductive potential and the Rumbi breed had superior growth. The Hamra breed showed better maternal skills in terms of fertility and prolificacy, while the Rumbi breed showed better lamb growth performance. Consequently, these results could be used for selective sheep breeding, taking into account the random effects of the environment and the potential of each breed., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: There is extensive interindividual variability in response and tolerance to anticancer drugs. This heterogeneity provides a major limitation to the "rational" use of cytotoxic drugs, and it becomes a major problem in oncology giving a narrow therapeutic window with a vital risk. Among these anticancer drugs, irinotecan can cause dose-limiting toxicities, commonly diarrhea and neutropenia. Interaction among pathways of activation/inactivation ( UGT1A1 ) and hepatobiliary transport of irinotecan and its metabolites could, in part, explain its interindividual variability. The objective of this study was to perform an exploratory analysis to evaluate the correlation between the genetic polymorphisms of UGT1A1 and ABCC2 with the different toxicities associated with irinotecan treatment. Materials and Methods: Seventy-five patients with solid cancers were included, all were administered an irinotecan-based regimen in both Mission Bay Medical Center; and Zuckerberg San Francisco General Hospital from May 2016 to December 2016. The patients' genotyping was performed for both the UGT1A1 *28 polymorphism, and the ABCC2  - 1549G>A, and ABCC2  - 1249G>A single nucleotide polymorphism. Comparisons among qualitative data were assessed using the χ 2 -test, and Fisher's exact test in the case of small group sizes. Results: Diarrhea was observed in 40 patients (53.3%), among them only 9 patients had high grades diarrhea (grades III and IV). Grades III/IV of nausea were more frequently associated with the ABCC2 -1549 AA genotype (83.3% p  = 0.004) in patients with colorectal cancer. In pancreatic cancer, a significant absence of diarrhea grades III-IV was noted in patients with the ABCC2 1249 GG genotype compared to the other ABCC2 1249 genotypes.

Objective: Irinotecan (CPT-11) is an important drug used in the treatment of several solid tumor types. To minimize its toxicity, therapeutic drug monitoring of CPT-11 and its major metabolites (SN-38, SN-38-glucuronide [SN-38G], and APC) has been proposed. We aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of CPT-11 and its major metabolites in plasma., Methods: Specimen preparation consisted of protein precipitation, evaporation, and reconstitution. Analyses were performed on a C18 column using reverse-phase gradient elution. Electrospray ionization and multiple reaction monitoring in positive mode were used for MS. The following heavy isotope-labeled internal standards were used: CPT-11 D10, SN-38 D3, SN-38G D3, and APC D3., Results: We found that CPT-11, SN-38G, and APC eluted at ~4.6 to 4.7 minutes, and SN-38 eluted at ~5.1 to 5.2 minutes. A second peak for SN-38 was detected at ~4.6 to 4.7 minutes. Given that the structure of SN-38 is found in CPT-11, SN-38G, and APC, and in the CPT-11 D10 used here, in-source fragmentation was the likely cause. In addition, we found that a low-level SN-38 impurity was present in CPT-11 D10 and to a lesser extent in SN-38 D3., Conclusion: When developing methods for CPT-11 and its metabolites, it is important to consider the effects of in-source fragmentation and the choice of internal standards., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ifosfamide-induced encephalopathy (IIE) is a rare and serious adverse reaction. Thus far, no standard medication has been documentedto be efficient in the reversal of IIE, and while ifosfamide infusion interruption and hydration are recommended, methylene blue (MB) administration remains controversial., Methods: We retrospectively reviewed medical records to assess cases with IIE after ifosfamide infusion. We included all patients having received an ifosfamide infusion during their hospitalization in the medical oncology unit of the National Institute of Oncology in Rabat, Morocco, between September 2016 and September 2017. We subsequently conducted a literature review to determine the role of MB in IIE by searching PubMed using the terms "Methylene Blue" and "Ifosfamide"., Results: A total of 88 patients received ifosfamide, and four patients had IIE. Ifosfamide infusion was stopped immediately after the IIE occurrence, and patients underwent renal function correction with hydration. All patients received MB infusion, and three patients had an improvement of their neurological status. As regards the literature review, 34 articles were reviewed and 16 items were included in the review. Overall, 38 (65.5%) patients received MB infusion and 28 (75.6%) patients responded favorably to the treatment., Conclusions: Methylene blue can be used as a treatment for IIE owing to the severity of the IIE as well as absence of standard medication. Nonetheless, side effects such as serotonergic syndrome should be investigated. More broadly, prospective studies and controlled trials are needed to explore the contribution of MB in IIE management and encourage its use.

Background: In front of the polymorphic bacterial ecology and antibiotic resistance in diabetic patients with foot infections and good patient care, collaboration between clinicians and microbiologists is needed to improve assessment and management of patients with this pathology., Objective: This study was designed to characterize the bacterial ecology of diabetic foot infection (DFIs) and to determine the different mechanisms of resistance involved., Methods: In this study bacterial strains and antibiotic resistance profiles were determined from diabetic foot infections patients ( n  = 117). The identification of resistance mechanisms, such as penicillinase and/or extended-spectrum β-lactamase production (ESBL), methicillin-resistant Staphylococcus aureus (MRSA) and efflux pump over-expression were performed., Results: A high prevalence of Gram-negative bacteria (61%) with Escherichia coli, and other Enterobacteriaceae and Pseudomonas aeruginosa being the predominant isolates. Gram positive bacteria mainly represented by Staphylococcus aureus accounted for 39% of the isolates. 93.5% of the Enterobacteriaceae were resistant to, at least, one molecule in the β-lactam family, while the majority of the Staphylococci were resistant to penicillin G and tetracycline (93.3% and 71.7%). The majority of non-fermenting Gram negative bacteria were also resistant to fluoroquinolones. β-lactamase detection tests revealed the presence of extended-spectrum β-lactamase in 43.5% of the Enterobacteriaceae, while methicillin-resistant Staphylococcus aureus represented 18.2% of the isolates. Additionally, 50.9% of non-fermenting Gram negative bacteria were overproducing efflux pumps., Conclusion: All Acinetobacter Baumannii were Multidrug-Resistant (MDR), as the majority of Staphylococci, and Enterobacteriaceae. These results should be taken into account by the clinician in the prescription of probabilistic antibiotic therapy in this context., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Springer Nature Switzerland AG 2020.)

Background: Colorectal Cancer (CRC) is a major health problem around the globe. In Morocco, the disease ranks third after breast and lung cancers. This study is the first in Morocco to investigate epidemiological, clinical and therapeutic features while exhaustively describing toxic side-effects to chemotherapy of CRC and studying the 3-years survivorship., Methods: This is a descriptive and analytical retrospective study of about 290 patients with CRC enrolled during the period of January-December 2013. Statistical analysis was performed to correlate clinicopathological data with chemotherapy toxicity and survivorship in patients, by Chi 2 test. Overall Survival (OS) rate has been calculated by the Kaplan-Meier method and compared using Log-rank test., Results: Fifty-five percent had a tumor localized in rectum, and 42,8% in colon. Mean age of these patients at diagnosis was 56,16 ± 14,6. incidence rate of adverse events (grade I to IV) was 85,6%. Diarrhea was the predominant toxicity (4.6%) occurring at a high grade (grade III-IV).The 3-years OS rate of patients with CRC was 71%. OS decreased by age, and patients with age subgroup between 40 to 59 years had a better OS than the other age subgroups (60 to 79 years and >80 years) with a p-value of 0.0001. Occurence of toxicity (all grades and types) was linked to a higher survival rates compared to the group who had no toxicity noticed (p-value of 0.001)., Conclusion: Our study shows that patients who had a polychemotherapy had a better OS than those who had monotherapy (p-value of 0.002)., (© 2019 Zineb A., et al.)

Catechol oxidase (PPO) was extracted and purified from Tadela (Phoenix dactylifera L.) date fruit, by a procedure that included (NH 4 ) 2 SO 4 precipitation followed by dialysis, Q-Sepharose bb ion-exchange chromatography and HPLC gel filtration chromatography. Some of its biochemical characteristics were studied. The purification rate and the yield were 80% and 20%, respectively. The Tadela date fruit catechol oxidase exhibited a molecular weight of 90 kDa using SDS-PAGE. The catechol oxidase showed only o‑diphenolase and triphenolase activities while no monophenolase activity was detected. A better affinity was observed using catechol as substrate (Km = 35 mM) with thus, a higher Vmax/Km ratio (80 U/mM·mL). This enzyme is thermostable in the temperature range (30-60 °C) with optimum activity in acidic range of pH. Four inhibitors were used for the control of enzymatic browning, of which sodium metabisulfite was the most potent (IC 50  = 0, 11 mM). The values of K I and mechanism of inhibition were also determined. No significant change on enzyme activity was noticed in the presence of metal ion and detergents. Therefore, thermal inactivation was studied in the temperature range between 60 and 80 °C using catechol as substrate. Their kinetic (K, D, t 1/2 , Zt, Ea) and thermodynamic (ΔH, ΔG and ΔS) parameters were also estimated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

An in vitro evaluation of the antimicrobial activity of essential oil (EO) and methanol extract (ME) from Algerian Nigella sativa L. seeds against microbial strains isolated from the oral cavities of periodontal patients was performed. Twelve Gram-positive bacteria, eleven Gram-negative bacteria and three microscopic fungi strains were isolated and identified. The antimicrobial activities of EO and ME were tested against Staphylococcus aureus , Staphylococcus epidermidis , Streptococcus pneumoniae , Enterococcus faecalis , Klebsiella pneumoniae , Proteus sp., Acinetobacter baumannii/calcoaceticus , Porphyromonas sp., Veillonella sp ., Candida sp. and Saccharomyces sp.. The total polyphenol and flavonoids contents of ME were higher than those of EO. Thin layer chromatography showed that catechin, gallic acid and quercetin were most likely present in the extracts. Fourier transform infrared spectrometry analysis (FT-IR) indicated the presence of bands from the CO groups of acids, alcohols, phenols, and ethers and the C[bond, double bond]O band of aldehydes. Analysis of the antimicrobial activity of N. sativa extracts obtained by the microdilution method showed excellent bactericidal activity of the essential oil and moderate efficiency of the ME against all the microbes tested. Staphylococcus epidermidis and Porphyromonas sp. were the most sensitive to EO (minimum bactericidal concentration (MBC): 16,500 μg/ml) at 48 h of incubation and, 125,000 μg/ml of ME was the most active against all the microbes tested. However, after18 or 24 h, this efficiency was decreased in some strains. In addition, Saccharomyces sp. and Candida albicans were more sensitive to EO than ME during the incubation, while this efficiency was clearly not visible with the agar well method, and most microbes tested presented remarkable resistance to these extracts., (© 2018 The Authors.)

Introduction: Centralized preparation of anticancer drugs meets quality and safety objectives. Its economic interest has been the subject of several studies, with very heterogeneous methodological approaches., Objective: This study evaluates the economic impact of the centralization of the preparation of chemotherapy in the national institute of oncology of Rabat, the referral institute in the management of cancer in Morocco., Materials and Methods: The analysis included 3000 preparations. It compared the costs of anticancer drugs in a centralized unit at theoretical costs in the healthcare units, modelled according to two approaches., Result: With a conservative approach, the impact of centralization was estimated at 80%. The centralized system made it possible to materialize 80% of the potential gain. The remaining 20% is considered a loss. It was very much related to the preparation of the expensive molecules (90%)., Conclusion: Centralization thus allows a better distribution of roles within the hospital and provides a source of self-financing for quality improvement., (Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Improvement of oat lines via introgression is an important process for food biochemical functionality. This work aims to evaluate the protective effect of phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on hyperglycemia-induced oxidative stress and to establish the possible mechanisms of antidiabetic activity by digestive enzyme inhibition. Eight phenolic acids were quantified in our samples including ferulic, p -hydroxybenzoic, caffeic, salicylic, syringic, sinapic, p -coumaric and chlorogenic acids. The Oat extract (2000 mg/kg) ameliorated the glucose tolerance, decreased Fasting Blood Glucose (FBG) and oxidative stress markers, including Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH) and Malondialdehyde (MDA) in rat liver and kidney. Furthermore, Metformin and Oat intake prevented anxiety, hypercholesterolemia and atherosclerosis in diabetic rats. In vivo anti-hyperglycemic effect of Oat extracts has been confirmed by their inhibitory activities on α-amylase (723.91 μg/mL and 1027.14 μg/mL) and α-glucosidase (1548.12 μg/mL & 1803.52 μg/mL) enzymes by mean of a mixed inhibition., Competing Interests: The authors declare no conflict of interest.

Rosmarinus officinalis L., a medicinal herb from the labiates family, has been reported to have potential benefit in the treatment and prevention of several diseases. In particular its phenolics have demonstrated protective effects on various types of cancer through several mechanisms. The present study aimed to determine the effects of rosemary phenolic extracts on human cell functions, with particular regard to their anti-proliferative properties in three cell types U937, CaCo-2 and the peripheral blood mononuclear cells (PBMCs). The radical scavenging and Ferric reducing abilities of the extracts have been assessed as well as their cyto-toxicity and effects on cell cycle distribution and apoptosis. About 13 compounds were identified with dominance of rosmarinic acid in the methanolic extract and phenolic diterpens in the ethyl acetate fraction (Carnosol, Carnosic acid and methyl Carnosate). The total polyphenolic content was important in the first extract with 2.589 ± 0.005 g/100 g in gallic acid equivalent compared to 0.763 ± 0.005 g/100 g. The methanolic fraction displayed higher antioxidant activity (DPPH IC50 : 0.510 mg/mL and FRAP: 1.714 ± 0.068 mmol Fe 2+ /g) while ethyl acetate showed pronounced antiproliferative effects (IC 50 : 14.85 ± 0.20µg/mL and 14.95 ± 2.32 µg/mL respectively for U937 and CaCo-2 cells). The anti-proliferative effect was associated with a cell cycle arrest in S phase for U937 (62% of the population at 5 µg/mL) with a concomitant decrease in G1 and G2/M phases. Tested extracts displayed in addition early apoptotic effects in U937 and late apoptosis in CaCo-2 cells. The obtained data indicate that the identified phenolics are at least partially responsible for the observed cytotoxicity.

A 48-year-old woman developed palmoplantar hyperkeratosis during treatment with imatinib (400mg/day) for treatment of chronic myeloid leukemia. After 5months of treatment, she developed plantar lesions with yellow-brownish plaques and palmar desquamations. The skin biopsy has eliminated psoriasis. Imatinib was discontinued, and treatment with an emollient balm and a soothing repair cream with an improvement of symptoms. A French imputability assessment score of I3 was obtained, indicating a probable relationship between the side effect and imatinib. In our case, the skin adverse events require definitive drug discontinuation and change of treatment., (Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Epstein-Barr virus-induced gene 3 (EBI3) is a subunit of the composite cytokines IL-27 and IL-35. Both have beneficial functions or effects in models of infectious and autoimmune diseases. This suggests that administration of EBI3 could be therapeutically useful by binding free p28 and p35 to generate IL-27 and IL-35. IL-27- and IL-35-independent functions of EBI3 could compromise its therapeutic uses. We therefore assessed the effects of EBI3 on cytokine receptor-expressing cells. We observed that EBI3 activates STAT3 and induces the proliferation of the IL-6-dependent B9 mouse plasmacytoma cell line. Analyses using blocking mAbs and Ba/F3 transfectants expressing gp130 indicate that EBI3 activity was linked to its capacity to mediate IL-6 trans -signaling, albeit less efficiently than soluble IL-6Rα. In line with this interpretation, co-immunoprecipitation and SPR experiments indicated that EBI3 binds IL-6. An important pro-inflammatory function of IL-6 trans -signaling is to activate blood vessel endothelial cells. We observed that EBI3 in combination with IL-6 could induce the expression of chemokines by human venal endothelial cells. Our results indicate that EBI3 can promote pro-inflammatory IL-6 functions by mediating trans -signaling. These unexpected observations suggest that use of EBI3 as a therapeutic biologic for autoimmune diseases will likely require co-administration of soluble gp130 to prevent the side effects associated with IL-6 trans -signaling. Together with previous studies that demonstrated activation of IL-6R by p28 (IL-30), new findings further suggest a complex interrelation between IL-27 and IL-6., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

This study investigates the accumulation and distribution of nickel in Arundo donax L. parts to assess the potential use of this plant in phytoremediation of Ni-contaminated soils. The effect of ethylene diamine tetra-acetic acid (EDTA) and nutrient solution containing NPK on the plant was proped. A 35-day pot experiment was performed in the laboratory and the pots were irrigated with Ni-contaminated solution combined or not with EDTA and NPK. The growth of plants was evaluated at the end of the experiment. The accumulation of Ni was analyzed by atomic absorption spectroscopy (AAS). The obtained results indicate that the plant was able to survive with high Ni content. The growth and the concentrations of Ni in the plant tissues were less affected. In the absence of the amendments, Ni was accumulated in the stems and leaves. However, the addition of NPK significantly reduced Ni concentration in the stems and leaves. The application of EDTA enhanced Ni uptake in roots. The translocation factor (TF) was greater than 1, which categorizes A. donax L. as a great candidate for Ni phytoextraction. A. donax L. is suitable for phytoremediation of Ni. This investigation contributes to the studies on the potential of phytoremediation technologies in Algeria.

The optimum conditions for acid activation of diatomite for maximizing bleaching efficiency of the diatomite in sun flower oil treatment were studied. Box-Behnken experimental design combining with response surface modeling (RSM) and quadratic programming (QP) was employed to obtain the optimum conditions of three independent variables (acid concentration, activation time and solid to liquid) for acid activation of diatomite. The significance of independent variables and their interactions were tested by means of the analysis of variance (ANOVA) with 95 % confidence limits (α = 0.05). The optimum values of the selected variables were obtained by solving the quadratic regression model, as well as by analyzing the response surface contour plots. The experimental conditions at this global point were determined to be acid concentration = 8.963 N, activation time = 11.9878 h, and solid to liquid ratio = 221.2113 g/l, the corresponding bleaching efficiency was found to be about 99 %.

Daphne gnidium L. (Thymeleacees) is a famous Moroccan plant with cancer-related ethnobotanical use. Previously, we demonstrated that ethyl acetate extract of D. gnidium had antiproliferative and pro-apoptotic potential on human breast tumor MCF-7 cells. The purpose of this study was to investigate if the antiproliferative effect of this extract was similar for different human cancer cell lines such as A549 lung cancer and SMMC-7721 hepatoma cells. Moreover, this work essentially focused on the intrinsic apoptotic signaling pathway. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide on A549 and SMMC-7721 cells. The characterization of the mechanisms involved in this effect was determined by lactate dehydrogenase test, apoptosis assays and western blot analyses. Our present study has shown that this extract strongly inhibited proliferation of A549 (IC50: 213 ± 15 μg/ml) and SMMC-7721 (IC50: 170 ± 13 μLg/ml) cells. The characterization of antiproliferative effect demonstrated that this extract was an apoptosis inducer in both cell lines tested. The results of western blot analyses have shown in SMMC-7721 cells that this extract activated caspase signaling triggered by the modulation of Bcl-2 family proteins. These findings suggest that this natural extract-induced effects may have novel therapeutic applications for the treatment of different cancer types.

Chemical investigation of the EtOAc extract of the fungus Chaetomium aureum, an endophyte of the Moroccan medicinal plant Thymelaea lythroides, afforded one new resorcinol derivative named chaetorcinol, together with five known metabolites. The structures of the isolated compounds were determined on the basis of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry as well as by comparison with the literature. All compounds were tested for their activity towards the Hsp90 chaperoning machine in vitro using the progesterone receptor (PR) and rabbit reticulocyte lysate (RRL). Among the isolated compounds, only sclerotiorin efficiently inhibited the Hsp90 machine chaperoning activity. However, sclerotiorin showed no cytotoxic effect on breast cancer Hs578T, MDA-MB-231 and prostate cancer LNCaP cell lines. Interestingly, deacetylation of sclerotiorin increased its cytotoxicity toward the tested cell lines over a period of 48 h., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: Aristolochia longa (from the family Aristolochiaceae) is widely used in Algerian traditional medicine. Here, we document ethnomedicinal uses by local population of Mascara province (West Algeria) and we evaluate the antifungal activity, the phytochemical composition and total phenolic content of aqueous extract (decoction) of the roots of A. longa from Algeria., Materials and Methods: The ethnobotanical investigation was carried out in Mascara Province (West Algeria). Antifungal activity was assessed against Saccharomyces cerevisiae. Total phenolic content was measured using the Folin-Ciocalteu's reagent., Results: Our results showed that A. longa is widely used to treat several ailments such as cancer (38%), skin infections (14%), and diabetes (11%). Crushed roots are commonly used (89%) mixed with honey, milk, water or other medicinal plants. A. longa aqueous extract induced growth inhibition of S. cerevisiae cells in a dose - and time - dependent manner. An effective suppression of S. cerevisiae (97.06% inhibition of proliferation) was obtained at the 500 µg/mL after 72 h. Results of the phytochemical screening revealed that A. longa aqueous extract contained various bioactive compounds, including polyphenols and flavonoids. Total phenolic content in A. longa aqueous extract was found to be 6.07 ± 0.12 mg (gallic acid equivalents)/g., Conclusion: A. longa may be considered as a promising source of new drugs for treating cancer and as a good antifungal agent.

Cancer is a leading cause of death worldwide accounting for 7.4 million deaths. Cancer has become a major public health concern in Algeria. The aim of the present study was to estimate cancer incidence in Mascara Province based on the population-based cancer registry. We analyzed data from the cancer registry of Mascara covering all cancer cases diagnosed by all methods and included in the registry from 1(st) January 2000 to 31(st) December 2010. The results are presented as incidence rates of cases by site, sex, age, and crude rate. Age-standardized rates per 100,000 person-years (ASRs) were calculated, using the direct method of standardization to the world population. A total of 1875 cases of invasive cancer were recorded. The mean age of diagnosis for all cancers was 52.66 ± 0.5 in men and 59.18 ± 0.6 in women. The ASR for all cancers in females was 27.8 per 100,000, and that for males was 23.6 per 100,000. The most important finding of the present study was the high incidence of liver cancer among males and females in Mascara. Among females, breast cancer was the most frequently reported followed by Cervix uteri, liver and colon. The most frequent cancer types in males were lung, colon, esophagus and stomach and liver. Cancer incidence in Mascara province was lower than that reported in other national and regional registries. Findings of the present study revealed high incidence of liver cancer in the province, the highest in Algeria, suggesting high prevalence of risk factors.

Cyproheptadine (Cph) is an antiserotoninergic and antihistaminergic agent with alpha-blocking activity and central sedative effect. Cph has been found to be effective in stimulating appetite, but to our knowledge, its direct effects on the intestine have not been documented. We aimed to assess the antisecretory effects of Cph in rat proximal colon using Ussing chambers' technique. In basal and serotonin (5-HT)-stimulated conditions, Cph induced a dose-dependent reduction in short-circuit current (Isc). This effect was different in fed vs. fasted rats (EC50 = 1.9 × 10(-5 ) m and 4.9 × 10(-5 ) m, respectively). As expected, Cph induced a marked dose-dependent rightward shift of the concentration-response curve to 5-HT (pA2 = 5.4). The effect of Cph was found to be close to that of antisecretory agents in the following sequence: peptide YY > somatostatin > clonidine > Cph > C7-sorbin. To our knowledge, this is the first demonstration that Cph has a direct effect on the inhibition of electrogenic ionic secretion in intestinal epithelium in vitro. Our results indicate that Cph can modulate the intestinal transport of electrolytes and provide a new insight into the peripheral effects of this drug, which is frequently prescribed as appetite stimulator in developing countries., (© 2013 The Authors Fundamental and Clinical Pharmacology © 2013 Société Française de Pharmacologie et de Thérapeutique.)

Aristolochia longa is widely used in traditional medicine in Algeria to treat breast cancer. The aim of the present study was to investigate the response of bone resorption markers to A. longa intake by Algerian breast cancer postmenopausal women. According to the A. longa intake, breast cancer patients were grouped into A. longa group (Al) (n = 54) and non-A. longa group (non-Al) (n = 24). 32 women constituted the control group. Bone resorption markers (from urine) pyridinoline (PYD) and deoxypyridinoline (DPD) were determined by HPLC. Serum and urinary creatinine, uric acid, and urea were measured. 1 g of A. longa intake resulted in significant rise of renal serum markers and a pronounced increase of bone resorption markers. The intake of A. longa roots is detrimental for kidney function and resulted in high bone resorption, maybe due to the reduction in renal function caused by the aristolochic acids contained in the roots.

A pollen analysis of Algerian honey was conducted on a total of 10 honey samples. The samples were prepared using the methodology described by Louveaux et al ., that was then further adapted by Ohe et al . The samples were subsequently observed using light microscopy. A total of 36 pollen taxa were discovered and could be identified in the analyzed honey samples. Seventy percent of the studied samples belonged to the group ofmonofloral honeys represented by Eucalyptus globulus , Thymus vulgaris , Citrus sp. and Lavandula angustifolia . Multifloral honeys comprised 30% of the honey samples, with pollen grains of Lavandula stoechas (28.49%) standing out as the most prevalent. Based on cluster analysis, two different groups of honey were observed according to different pollen types found in the samples. The identified pollen spectrum of honey confirmed their botanical origin.

Ethnopharmacological Relevance: Salvadora persica L. (miswak) is traditionally used to ensure oral hygiene Muslim people in developing countries where it is growing. The antibacterial properties of Salvadora persica L. originating from various geographic areas have already been reported. However, they have never been tested for samples originating from Hoggar, where extreme weather conditions could lead to different properties for this Salvadora persica L. ecotype., Aim of the Study: To assess the in vitro and in vivo antimicrobial activities of methanolic extract of Algerian Hoggar Salvadora persica L. (miswak) on some isolated and identified strains from the oral cavity of school children aged from 6 to 12 with (n=20) and without (n=20) caries., Materials and Methods: After a qualitative and quantitative analysis of dental plaque samples from the selected children, the effect of methanolic extract of Hoggar miswak against oral bacterial and fungal strains isolated from the oral cavity of children with caries was tested by both agar disc diffusion and microdilution methods. The stability and physicochemical parameters of Hoggar Salvadora persica L. mouthwash were also assessed compared. The in vivo antimicrobial effect of Hoggar miswak rinse on dental plaque samples was also tested over a week., Results: Four bacterial genera (Staphylococcus, Streptococcus, Escherichia and Lactobacillus) were commonly identified in all subjects at different colonization levels. A statistically significant difference in colonization levels between the two groups of children was recorded. Hoggar miswak extract more significantly inhibited the growth of Gram negative bacteria from the dental plaque than Gram positive ones. Hoggar Salvadora persica L. mouthwash was stable at 4 °C and 25 °C over the period of conservation (one week) while a temperature of 40 °C induced variations in the physicochemical parameters and considered not suitable for preservation. The in vivo study revealed a significant reduction in bacteria of the oral cavity using miswak mouthwash as compared to placebo., Conclusion: Hoggar miswak extract displayed a strong antimicrobial effect both in vitro and in vivo. Its use as a mouthrinse could therefore be recommended as a preventive measure to preserve from tooth decay., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

To relieve respiratory problems such as apnea in newborns, caffeine citrate is the drug of choice because of its good tolerance and therapeutic index. However, its impact on the intestinal microbial ecosystem and on bacterial translocation in the neonatal period remains insufficiently investigated. Therefore, the objective of this study was to evaluate the effects of caffeine citrate on the establishment of the intestinal microflora and bacterial translocation in rats from birth to the 30th day of life. Newborn Wistar rats were divided into four groups of 14 animals, each subdivided into a control group receiving a placebo (12mL tap water/kg/day) and another treated with caffeine citrate (12mg/kg/day). The animals were nursed by their mothers and weighed daily. A group of 14 rats was killed at birth and after 10, 20, or 30 days of life. Organs in which translocation was assessed (liver, lungs, spleen, and kidneys) and various fragments of intestine (duodenum, jejunum, ileum, and colon) were surgically removed. The bacteriological analysis performed involved enumeration of the total microflora, staphylococci, enterobacteria, and lactobacilli. From the 10th day, caffeine was shown to significantly decrease the weight of treated animals as compared with controls (P<0.05). However, caffeine treatment did not drastically alter the kinetics of establishment of the intestinal microflora as only enterobacteria were found to be significantly lower in any intestinal segment of the treated group (P<0.05). Moreover, from the 20th day of life, caffeine citrate significantly downregulated bacterial translocation of both Gram-positive and -negative bacteria (P<0.05). This preliminary study on the effects of treatment with caffeine citrate may open opportunities in clinical pediatrics; the treatment will remain partially effective in preventing bacterial translocation in the neonatal period., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancers; it belongs to the genus Bryonia (Cucurbitaceae)., Aim of the Study: To investigate the cytotoxic and apoptogenic activities, the phytochemical composition and acute toxicity of the aqueous extract of Bryonia dioica roots growing in Algeria., Materials and Methods: Dried roots of Bryonia dioica were extracted with water (decoction). The cytotoxic effects of the aqueous extract in the Burkitt's lymphoma BL41 cell lines were evaluated by flow cytometry. Apoptosis induction was assessed by two corroborative assays; propidium iodide (PI) staining of cell DNA and flow cytometric light scatter analysis. The mitochondria membrane potential was investigated using a fluorescent dye DIOC6. The expression of caspases-3, -8, -9 and PARP was assessed by Western blot. The phytochemical screening of the roots of Bryonia dioica was performed using qualitative phytochemical standard procedures., Results: The Bryonia dioica aqueous extract induced cell death in a dose-dependent manner. The IC50 of Bryonia dioica aqueous extract was estimated to be approximately 15, 63μg/ml. This was accompanied by induction of apoptosis, activation of caspase-3 and -9, cleavage of PARP and loss of mitochondria membrane potential. Furthermore, the phytochemical screening of roots of Bryonia dioica showed the presence of various bioactive such as polyphenols, sterols and triterpenes, alkaloids, c-heterosides, carbohydrates and saponins., Conclusion: The aqueous extract of Bryonia dioica induces apoptosis in the Burkitt's lymphoma BL41 cell lines via the mitochondrial pathway. The flavonoids, sterols and triterpens detected could be responsible for the cytotoxic and apoptogenic activities of the aqueous extract of Bryonia dioica. These findings suggest that Bryonia dioica could be considered as a promising source for developing novel therapeutics against Burkitt's lymphoma., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Atractylis L gummifera is a plant that causes every year serious and often deadly poisonings. In Morocco, 153 cases of poisoning have been recorded between January 1980 and June 1995 by the Moroccan Antipoison Centre. The ignorance by the clinicians, the fast evolution and the frequency of these poisonings are the origin of diagnosis problems. The solution of those problems is to detect atractyloside and carboxyatractyloside in the biologic liquids. Since several decades, some toxicological analytical methods were established in view of an assay. The aim of our paper is to describe the poisoning by this plant and to review the methods of toxicological analysis used from the colorimetric technique until the news recent chromatographic methods.

The adsorption of Cu(2+), Zn(2+), Cd(2+) and Pb(2+) ions from aqueous solution by Algerian raw diatomite was studied. The influences of different sorption parameters such as contact pH solution, contact time and initial metal ions concentration were studied to optimize the reaction conditions. The metals ions adsorption was strictly pH dependent. The maximum adsorption capacities towards Cu(2+), Zn(2+), Cd(2+) and Pb(2+) were 0.319, 0.311, 0.18 and 0.096 mmol g(-1), respectively. The kinetic data were modelled using the pseudo-first-order and pseudo-second-order kinetic equations. Among the kinetic models studied, the pseudo-second-order equation was the best applicable model to describe the sorption process. Equilibrium isotherm data were analysed using the Langmuir and the Freundlich isotherms; the results showed that the adsorption equilibrium was well described by both model isotherms. The negative value of free energy change ΔG indicates feasible and spontaneous adsorption of four metal ions on raw diatomite. According to these results, the high exchange capacities of different metal ions at high and low concentration levels, and given the low cost of the investigated adsorbent in this work, Algerian diatomite was considered to be an excellent adsorbent.

The antidiabetic effect of N. sativa seed ethanol extract (NSE) was assessed in Meriones shawi after development of diabetes. Meriones shawi were divided randomly into four groups: normal control, diabetic control, diabetic treated with NSE (2 g eq plant/kg) or with metformin (300 mg/kg) positive control, both administered by daily intragastric gavage for 4 weeks. Glycaemia and body weight were evaluated weekly. At study's end, an Oral Glucose Tolerance Test (OGTT) was performed to estimate insulin sensitivity. Upon sacrifice, plasma lipid profile, insulin, leptin, and adiponectin levels were assessed. ACC phosphorylation and Glut4 protein content were determined in liver and skeletal muscle. NSE animals showed a progressive normalization of glycaemia, albeit slower than that of metformin controls. Moreover, NSE increased insulinemia and HDL-cholesterol, compared to diabetic controls. Leptin and adiponectin were unchanged. NSE treatment decreased OGTT and tended to decrease liver and muscle triglyceride content. NSE stimulated muscle and liver ACC phosphorylation and increased muscle Glut4. These results confirm NSE's previously reported hypoglycaemic and hypolipidemic activity. More significantly, our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulin-independent AMPK signaling pathway, and by enhancing muscle Glut4 expression.

Metformin is an orally administered drug that lowers blood glucose and improves insulin sensitivity in patients with non insulin-dependent diabetes. Although the antihyperglycemic effect of metformin has been extensively studied, its cellular mechanism(s) of action (including the effect on enterocyte) remains to be defined. This study was designed to examine the effect of metformin on glucose transporters in enterocyte. Na(+)-dependent glucose transporter-1 (SGLT-1) activity was followed as glucose-induced short-circuit current (Isc) in Ussing chambers. The effect of metformin (10 micromol/L, 3 min) on transmural glucose transport was studied in isolated rat jejunal loops. Its impact on abundance of transporters SGLT-1 and GLUT2 in jejunal brush border membranes (BBM) and its effect on the phosphorylation of AMP-activated protein kinase (AMPK) alpha2 subunit was studied by western blot. Acute effect of metformin was also measured in vivo by oral glucose tolerance test (OGTT). Metformin markedly inhibited glucose-induced Isc (approximately 77%) after mucosal addition. In addition, metformin reduced the glucose-induced abundance of SGLT-1 in BBM and increased those of GLUT2, concomitantly increasing the phosphorylation of intracellular AMPKalpha2. This effect of metformin was also observed using non-metabolizable sugar alpha3-O-methyl glucose. Transmural glucose transport measured in vitro was increased by 22% under metformin. Finally, oral metformin markedly increased glucose tolerance in OGTT. In conclusion, metformin slightly increases intestinal glucose absorption by inducing a re-distribution of glucose transporters in BBM through AMPK control in enterocyte. In addition to its action to other splanchnic tissues, this could constitute a peripheral signal contributing to the beneficial effect of metformin on glucose tolerance.

Aim of the Study: Nigella sativa L. (Ranunculaceae) seeds have been used traditionally for centuries, notably for treating diabetes., Materials and Methods: We studied the effects of the crude aqueous extract of Nigella sativa seeds on intestinal glucose absorption in vitro using a short-circuit current technique and in vivo using an oral glucose tolerance test., Results: The aqueous extract of Nigella sativa (0.1 pg/ml to 100 ng/ml) exerted dose-dependent inhibition of sodium-dependent glucose transport across isolated rat jejunum. Maximal inhibition exceeded 80% and IC50 was close to 10 pg/ml. An oral glucose tolerance test was carried out in rats after the initial dose and after a 6-week treatment of Nigella sativa (2 g/(kg day)), and compared to metformin (300 mg/(kg day)). Chronic Nigella sativa treatment improved glucose tolerance as efficiently as metformin. Nigella sativa and metformin also reduced body weight without any toxic effect., Conclusions: To our knowledge, this is the first demonstration that Nigella sativa directly inhibits the electrogenic intestinal absorption of glucose in vitro. Together with the observed improvement of glucose tolerance and body weight in rats after chronic oral administration in vivo, these effects further validate the traditional use of Nigella sativa seeds against diabetes.

Incidence of type II diabetes is rapidly increasing worldwide. In order to identify complementary or alternative approaches to existing medications, we studied anti-diabetic properties of Vaccinium angustifolium Ait., a natural health product recommended for diabetes treatment in Canada. Ethanol extracts of root, stem, leaf, and fruit were tested at 12.5 microg/ml for anti-diabetic activity in peripheral tissues and pancreatic beta cells using a variety of cell-based bioassays. Specifically, we assessed: (1) deoxyglucose uptake in differentiated C2C12 muscle cells and 3T3-L1 adipocytes; (2) glucose-stimulated insulin secretion (GSIS) in beta TC-tet pancreatic beta cells; (3) beta cell proliferation in beta TC-tet cells; (4) lipid accumulation in differentiating 3T3-L1 cells; (5) protection against glucose toxicity in PC12 cells. Root, stem, and leaf extracts significantly enhanced glucose transport in C2C12 cells by 15-25% in presence and absence of insulin after 20 h of incubation; no enhancement resulted from a 1 h exposure. In 3T3 cells, only the root and stem extracts enhanced uptake, and this effect was greater after 1 h than after 20 h; uptake was increased by up to 75% in absence of insulin. GSIS was potentiated by a small amount in growth-arrested beta TC-tet cells incubated overnight with leaf or stem extract. However, fruit extracts were found to increase 3H-thymidine incorporation in replicating beta TC-tet cells by 2.8-fold. Lipid accumulation in differentiating 3T3-L1 cells was accelerated by root, stem, and leaf extracts by as much as 6.5-fold by the end of a 6-day period. Stem, leaf, and fruit extracts reduced apoptosis by 20-33% in PC12 cells exposed to elevated glucose for 96 h. These results demonstrate that V. angustifolium contains active principles with insulin-like and glitazone-like properties, while conferring protection against glucose toxicity. Enhancement of proliferation in beta cells may represent another potential anti-diabetic property. Extracts of the Canadian blueberry thus show promise for use as a complementary anti-diabetic therapy.

Type II diabetes is a major health problem worldwide. Some populations, such as aboriginal peoples, are particularly at risk for this disease. In the Cree Nation of Quebec, Canada, prevalence in adults is approaching 20%, and the consequences are compounded by low compliance with modern medicine. In 2003, we conducted an ethnobotanical study of Cree medicinal plants used for the treatment of symptoms of diabetes. This served as the basis for a project designed to identify efficacious complementary treatment options more readily accepted by this population. The present study assesses the in vitro anti-diabetic potential of extracts from the 8 most promising plants to emerge from the ethnobotanical study. Cell-based bioassays were employed to screen for (i) potentiation of glucose uptake by skeletal muscle cells (C2C12) and adipocytes (3T3-L1); (ii) potentiation of glucose-stimulated insulin secretion (GSIS) and insulin production by pancreatic beta cells (INS 832/13); (iii) potentiation of triglyceride accumulation in differentiating 3T3-L1 cells; (iv) protection against glucose toxicity and glucose deprivation in pre-sympathetic neurons (PC12-AC). Additionally, anti-oxidant activity was measured biochemically by the diphenylpicrylhydrazyl (DPPH) reduction assay. All plant extracts potentiated basal or insulin-stimulated glucose uptake to some degree in muscle cells or adipocytes. Adipocyte differentiation was accelerated by 4 extracts. Five extracts conferred protection in PC12 cells. Three extracts displayed free radical scavenging activity similar to known anti-oxidants. None of the plant extracts enhanced GSIS or insulin content in INS 832/13 beta cells. It is concluded that the Cree pharmacopoeia contains several plants with significant anti-diabetic potential.

None of the currently used methods to evaluate bone resorption by osteoclasts cultured on bone substrate measures directly the amounts of degraded bone collagen, which is a direct reflection of the osteoclast "work done." We therefore propose a reliable biochemical method to evaluate the in vitro collagenolysis process. Bone-resorbing activity was evaluated, after HPLC separation, by fluorimetric measurement of hydroxylysylpyridinoline (HP), a collagen cross-link molecule, released in culture supernatants. We first confirm previous data reporting that HP is released in the culture medium in a peptide-conjugated form. After acid hydrolysis, we show that HP is highly correlated with the lacunae area (r = 0.68, P<0.0001) and with the amounts of antigenic collagen fragments (Cross-laps for culture) released in culture medium (r = 0.77, P<0.0002). Using a cysteine protease inhibitor, we observed that lacunae areas are dramatically less inhibited (35% inhibition) than the release of bone-degraded products, including HP and antigenic collagen fragments (96 and 92% inhibition, respectively). Coupled to the resorbed area measurement, biochemical evaluations offer both quantitative and qualitative complementary measurements of the osteoclastic bone-resorbing process., (Copyright 2000 Academic Press.)

Little is known about the photodegradation of pyridinoline (Pyd) and deoxypyridinoline (Dpd), which are two mature cross-links stabilizing collagen within extracellular matrix. In this study, highly purified free Pyd and Dpd cross-links have been degraded by irradiation with ultraviolet light and we have shown that photolysis varies with the pH value. Assessment of photolysis in basic (pH 9) and neutral (pH 7) solutions by high-performance liquid chromatography as well as by UV absorbance measurement indicates that both cross-links are degraded after a 24 h UV exposure, while in acidic solution (pH 3) only Dpd is photolysed, suggesting that acid pH provides major protection against Pyd photolysis. Photodegradation products have been studied by amino-acid and mass spectral analysis. Both methods confirm the lack of Pyd degradation in acid pH. Furthermore, amino-acid analysis allows us to identify hydroxylysine and lysine as a result of Pyd and Dpd photolysis, respectively, indicating that the mechanism of photodegradation involves the cleavage of the pyridinium ring on each side of the quaternary nitrogen. Finally, we have also studied the photolysis of different molecular species of type I collagen peptides, obtained by digestion with collagenase of demineralized turkey bone. Our results indicate that even when they are part of the structure of collagen peptide, Pyd and Dpd can be photolysed. However, we have shown that the larger the peptide is, the smaller are the effects of UV irradiation.

Significant progress has been made in recent years in the development of new bone resorption markers, based principally on the urinary excretion of pyridinoline (Pyd) and deoxypyridinoline (Dpd) crosslinks. For their measurement, in spite of the recent development of immunoassays, HPLC remains the method of reference. However, the lack of an appropriate internal standard requires large amounts of pure crosslinks for external standardisation. Herein, we describe an efficient method for the isolation of both crosslinks from bone of adult turkey by isocratic semi-preparative HPLC. Demineralized bone is hydrolysed in hydrochloric acid, 9 M. A first liquid extraction step in butanol allowed to eliminate less polar compounds. The aqueous phase was concentrated and separated by gel filtration on Biogel P2 and eluted by acetic acid solution (10%). Fractions containing pyridinoline were pooled, concentrated, and purified on a CF1 cellulose column. Pyd and Dpd crosslinks were then separated isocratically by HPLC on a C18 reversed phase column (Vydac 218 TP 1010, 250x10 mm) and eluted with HFBA as the ion-pairing agent. Retention times of Pyd and DPD were 23.6 and 28.7 min, respectively. Both crosslinks prepared by HPLC were then transformed as hydrochloride to cellulose phosphate and desalted on Sephadex G-10 columns. These two further steps yielded highly purified compounds (the purity was greater than 98% evaluated by aminoacid analysis). In conclusion, the efficiency of this method allows to obtain rapidly Pyd and Dpd without interfering compounds as proven by spectral studies (NMR and mass spectroscopy).

We investigated the response of bone-specific resorption markers in fasting urine samples from postmenopausal women with low daily dietary calcium (Ca) intake (<800 mg/day) who received either Ca supplementation (1200 mg/day, n = 18) or placebo (n = 14) for 2 months. We measured urinary hydroxyproline, total pyridinoline, and deoxypyridinoline by HPLC, and free deoxypyridinoline (i-F-Dpd) and N- and C-telopeptide fragments of type I collagen (NTX and CTX) by immunoassays. Before supplementation, the urine concentrations of bone resorption markers in the 32 subjects were not statistically different from those measured in 21 subjects with daily dietary Ca intake >800 mg/day. In contrast to the placebo group, Ca supplementation decreased all collagen-related degradation markers except i-F-Dpd as early as the first month. The magnitude of response after 2 months of Ca supplementation, expressed as mean percentage of decrease from baseline values or as individual Z scores, was greatest for the telopeptide assays. Furthermore, the percentage of change assessed at 2 months was greater than the within-person biological variability (CV) assessed in the placebo-treated women for NTX and CTX, whereas for the other markers the percentage of change was very close of the within-person CVs. We conclude that cross-linked telopeptide fragments of type I collagen most sensitively reflect the change in bone resorption after Ca supplementation.

The measurement of urinary deoxypyridinoline (DPD) constitutes a specific and sensitive marker of bone resorption. Total and free forms of DPD are determined by chromatographic method (HPLC) after or without hydrolysis of urine, respectively. Pyrilinks-D, a new immunoassay, allows to assess directly the free forms and needs an appropriate hydrolysis step for measuring the total form. We have compared the values of free (F), total (T) and conjugated (NF) forms of DPD determined by HPLC and Pyrilinks-D, in elderly women (n = 21, mean age: 83.5 +/- 1.5 years) with vitamin D insufficiency (25 OH D < 6 ng/mL) and Ca insufficiency responsible for a secondary hyperparathyroidism (iPTH = 45.3 +/- 22.7 pg/mL) and in healthy elderly women (n = 25, mean age: 76.6 +/- 3.1 years) with a normal vit D status (25 OH D > 10 ng/mL) as control group. We have also measured DPD during the course of vit D and Ca supplementation. At baseline, the HPLC and Pyrilinks-D values of DPD/Cr are highly correlated (DPD-T: r = 0.92, p < 0.001 and DPD-F: r = 0.76, p < 0.001), DPD-F and -NF values are correlated with those of DPD-T, while DPD-F and -NF are not correlated between themselves. In elderly with vit D insufficiency, the values obtained with Pyrilinks-D as compared to control subjects, show a significant increase of urinary excretion of DPD-F (8.5 +/- 3.1 vs 5.7 +/- 1.9 nmol/mmol, Cr, p < 0.0001), DPD-T (16.8 +/- 10.2 vs 9.9 +/- 3.5 nmol/mmol, Cr; p < 0.001) and DPD-NF (8.3 +/- 9.0 vs 4.5 +/- 3.3 nmol/mmol, Cr, p < 0.05). The administration of 800 IU of vit D and 1 g of elemental Ca during a course of 6 months normalize the iPTH values (24.4 +/- 11.8 and 30.9 +/- 14.6 pg/mL at 3 and 6 months). Simultaneously, the urinary excretion at 3 and 6 months of DPD-T (12.9 +/- 6.0 and 13.6 +/- 6.5 nmol/mmol, Cr) and of DPD-NF (4.5 +/- 3.3 and 5.5 +/- 4.8 nmol/mmol Cr) assessed by Pyrilinks-D as well as by HPLC decreased significantly, while no change was seen with DPD-F assessed by both methods. The decreases expressed as percent of baseline values were about 20% for DPD-T and more than 30% for DPD-NF, while DPD-F levels remain unchanged. We conclude that the Pyrilinks-D immunoassay presents reliable characteristics and allows to assess either free or total forms of DPD, like the HPLC technique. It constitutes an excellent reflection of bone resorption in elderly with vit D insufficiency. However its application to monitor therapy like vit D and Ca supplementation, needs a hydrolysis step to determine DPD-T which appears in this study more sensitive to the treatment than DPD-F.