COMPARATIVE TOXICITY STUDY OF CHLOROQUINE AND HYDROXYCHLOROQUINE ON ADULT ALBINO RATS

Expanded use of Chloroquine and hydroxychloroquine drugs for non-malarial disease entities has resulted in prolonged duration of therapy and higher daily dosages leading to cumulative doses greater than those used in antimalarial therapy. The aim of the study is to evaluate and compare the toxic effects of chloroquine and hydroxychloroquine on different organs of albino rats. The study was conducted on 60 normal albino rats divided into 3 groups, the 1st group is the control group that received only distilled water, the 2nd and the 3rd group were given a single daily oral doses equivalent to 1/10th of LD50 chloroquine and hydroxychloroquine respectively. Assessment of liver and kidney functions, and histopathological changes in liver, kidney, and heart in different groups was done. The chloroquine treated group showed significant elevation of serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin (TB), serum creatinine-urea (Cr-U), Creatine Kinase-MB, C-reactive protein and Malonic dialdehyde levels as compared to control and hydroxychloroquine treated group. The histopathological evaluation showed marked hydropic degeneragtion, vascular congestion, interstitial hemorrhage, and necrosis in the liver, kidney and heart of chloroquine treated group, while hydroxychloroquine treated group showed mild congestion and slight cellular degeneration. Thus, hydroxychloroquine is less toxic and physicians should prescribe it better than chloroquine. Chloroquine if prescribed for therapeutic uses should be taken for short periods

COMPARATIVE TOXICITY STUDY OF CHLOROQUINE AND HYDROXYCHLOROQUINE ON ADULT ALBINO RATS

Expanded use of Chloroquine and hydroxychloroquine drugs for non-malarial disease entities has resulted in prolonged duration of therapy and higher daily dosages leading to cumulative doses greater than those used in antimalarial therapy. The aim of the study is to evaluate and compare the toxic effects of chloroquine and hydroxychloroquine on different organs of albino rats. The study was conducted on 60 normal albino rats divided into 3 groups, the 1st group is the control group that received only distilled water, the 2nd and the 3rd group were given a single daily oral doses equivalent to 1/10th of LD50 chloroquine and hydroxychloroquine respectively. Assessment of liver and kidney functions, and histopathological changes in liver, kidney, and heart in different groups was done. The chloroquine treated group showed significant elevation of serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin (TB), serum creatinine-urea (Cr-U), Creatine Kinase-MB, C-reactive protein and Malonic dialdehyde levels as compared to control and hydroxychloroquine treated group. The histopathological evaluation showed marked hydropic degeneragtion, vascular congestion, interstitial hemorrhage, and necrosis in the liver, kidney and heart of chloroquine treated group, while hydroxychloroquine treated group showed mild congestion and slight cellular degeneration. Thus, hydroxychloroquine is less toxic and physicians should prescribe it better than chloroquine. Chloroquine if prescribed for therapeutic uses should be taken for short periods

GENE POLYMORPHISM FOR Α-RECEPTOR OF OESTROGENES AND ALTERATIONS IN BONE MINERAL DENSITY FOR ADULT CELIAC DISEASE PATIENTS

It is well known that osteopenia and osteoporosis are frequently found celiac disease patients presenting classical symptoms of malabsorption1. Osteomalacia cases have also been diagnosed in celiac patients who do not present clinical signs of malabsorption , in patients with latent celiac disease, as well as in first degree relatives of patients with celiac disease who do not suffer from celiac disease themselves. This suggests the presence of different pathogenic mechanisms2. The analysis of genetic polymorphism represents an effective approach for an in-depth screening of genes potentially implicated in the development of osteoporosis. Because of the central role that estrogen plays in bone metabolism, ER genes play an important role in the determination of bone mineral density and the risk of osteoporosis. The fact that osteoporotic phenotypes are observed in patients with a destructive mutation of the α receptor gene for estrogen together with the signs of reduced bone mineral density that are found in mice presenting a functional insufficiency of ER α, but not in mice showing reduced ER β function, demonstrates that ER α is one of the principal genes involved in the genesis of osteoporosis3. Previously , two intronic polymorphisms of the α ER gene, identified by restriction endonucleases PvuII and TA Xba and repetitive polymorphism sequences, have been linked to bone mass density in the Japanese population and in menopausal Italian women4

BLOOD LIPID DISORDER IN MEN WITH INCREASED WAIST CIRCUMFERENCE COMPARED TO MEN HAVING NORMAL WAIST CIRCUMFERENCE WITHIN THE SAME CATEGORY OF BMI

Background: No local studies have been performed yet to investigate the influence of central or abdominal obesity on serum lipids in men having increased Waist Circumference (WC) compared to men with normal Waist Circumference values within the same BMI (Body Mass Index) category. Objective:To examine whether the prevalence of dyslipidemia, (defined as Hypercholesterolemia (Total Cholesterol level ≥240 mg/dl), high LDL-C level (≥160 mg/dl), low HDL-C level (<35 mg/dl), or Hypertriglyceridemia (TG level ≥200 mg/dl)), is higher in men having high Waist Circumference compared to others with normal WC values within the same BMI category. Methods: The study was conducted between September 2013 and July 2014. Eighty-eight overweight men (BMI = 25-29.9) were grouped by WC as follows: 28 with high values (>102 cm) and 60 with normal values (≤ 102cm). Blood samples were drawn and assayed for total cholesterol, triglyceride, HDL-C, and LDL-C,at the department of Laboratory in the Faculty of Public Health, Lebanese University. All assays were performed by enzymatic colorimetric methods using Hitachi-704. Results: Overweight men with high WC values (according to cutoff points internationally adopted) were the most likely to have dyslipidemia with its subsequent increased health risk compared with those having normal WC values. Conclusion: we showed in this study that the prevalence of dyslipidemia in men with high WC values is greater compared to those with normal WC values within the same BMI category. This finding leads us to the importance of the incorporated evaluation of WC in addition to the BMI in clinical practice

Coupling by means of strong discontinuity approach between crack opening and gas permeability for concrete

Due to industrial needs, one of the key issues nowadays is to develop numerical tools that are able to predict the leakage rate through a cracked concrete structure. This paper presents a validation of a numerical modelling of leakage rate through a mortar specimen in a splitting test versus experimental results. The mechanical state of the material is described by means of an enhanced non-local damage model which takes into account the stress state and provides a realistic damage field at failure. A semi discrete method based on a Strong Discontinuity (SD) approach is then considered to study the coupling between the mechanical state of the material and its permeability. This method consists in first determining the crack opening field in the crack surface, then coupling the permeability with the crack opening by means of a modified Poiseuille's law. The assessed crack openings given by the SD method is compared to Digital Image Correlation measurements. The comparison between the two shows that the assessed crack openings given by SD are in good agreement (the maximum relative error is less than 20%). The results of the coupling compared to experimental data show a good estimation of the structural permeability for high level of cracking. Moreover, for lower levels of cracking, low differences between numerical and experimental permeabilities are observed

BLOOD LIPID DISORDER IN MEN WITH INCREASED WAIST CIRCUMFERENCE COMPARED TO MEN HAVING NORMAL WAIST CIRCUMFERENCE WITHIN THE SAME CATEGORY OF BMI

Background: No local studies have been performed yet to investigate the influence of central or abdominal obesity on serum lipids in men having increased Waist Circumference (WC) compared to men with normal Waist Circumference values within the same BMI (Body Mass Index) category. Objective:To examine whether the prevalence of dyslipidemia, (defined as Hypercholesterolemia (Total Cholesterol level ≥240 mg/dl), high LDL-C level (≥160 mg/dl), low HDL-C level (<35 mg/dl), or Hypertriglyceridemia (TG level ≥200 mg/dl)), is higher in men having high Waist Circumference compared to others with normal WC values within the same BMI category. Methods: The study was conducted between September 2013 and July 2014. Eighty-eight overweight men (BMI = 25-29.9) were grouped by WC as follows: 28 with high values (>102 cm) and 60 with normal values (≤ 102cm). Blood samples were drawn and assayed for total cholesterol, triglyceride, HDL-C, and LDL-C,at the department of Laboratory in the Faculty of Public Health, Lebanese University. All assays were performed by enzymatic colorimetric methods using Hitachi-704. Results: Overweight men with high WC values (according to cutoff points internationally adopted) were the most likely to have dyslipidemia with its subsequent increased health risk compared with those having normal WC values. Conclusion: we showed in this study that the prevalence of dyslipidemia in men with high WC values is greater compared to those with normal WC values within the same BMI category. This finding leads us to the importance of the incorporated evaluation of WC in addition to the BMI in clinical practice

Multispacer sequence typing of Coxiella burnetii from milk and hard tick samples from ruminant farms in Lebanon

his study was carried out to detect and characterize Coxiella burnetii in ruminant milk samples and in different tick species from seropositive farms in four Lebanese regions. Milk and tick samples were screened for C. burnetii presence by quantitative real-time PCR (qPCR) targeting IS1111 region followed by multispacer sequence typing (MST). The overall positive percentages of 9.6% (27/282) and 95.45% (84/88) for C. burnetii were recorded in ruminant milk and tick samples, respectively. In detail, the C. burnetii DNA was recorded in 52/54 (96.3%) of Rhipicephalus annulatus, 20/21 (95.24%) of Rhipicephalus turanicus, 6/6 (100%) of Hyalomma anatolicum, 5/6 (83.3%) of Rhipicephalus sanguineus and 1/1 of Rhipicephalus bursa. After genotyping of some IS1111-positive samples (17/111), different MST genotypes were identified. Out of 15 positive ticks, 10 were infected with MST2 genotype, 4 were infected with MST7 genotype and 1 was infected with MST57. Moreover, genotypes MST20 and MST58 were found in one cow and one goat milk samples, respectively. The present study confirmed the high genetic diversity of C. burnetii in Lebanon

Cytotoxic innate intraepithelial lymphocytes control early stages of Cryptosporidium infection

BackgroundIntraepithelial lymphocytes (IELs) are the first immune cells to contact and fight intestinal pathogens such as Cryptosporidium, a widespread parasite which infects the gut epithelium. IFN-γ producing CD4+ T IELs provide an efficient and a long-term protection against cryptosporidiosis while intraepithelial type 1 innate lymphoid cells limits pathogen spreading during early stages of infection in immunodeficient individuals. Yet, the role of T-cell like innate IELs, the most frequent subset of innate lymphocytes in the gut, remains unknown.MethodsTo better define functions of innate IELs in cryptosporidiosis, we developed a co-culture model with innate IELs isolated from Rag2-/- mice and 3D intestinal organoids infected with C. parvum using microinjection.ResultsThanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IELs secrete IFN-γ in response to C. parvum, the cytokine was not sufficient to inhibit parasite proliferation at early stages of the infection. The rapid protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis of the Cryptosporidium-infected organoids revealed that epithelial cells down regulated Serpinb9b, a granzyme inhibitor, which may increase their sensitivity to cytolytic attack by innate IELs.ConclusionBased on these data we conclude that innate IELs, most likely T-cell-like innate IELs, provide a rapid protection against C. parvum infection through a perforin/granzymes-dependent mechanism. C. parvum infection. The infection may also increase the sensitivity of intestinal epithelial cells to the innate IEL-mediated cytotoxic attack by decreasing the expression of Serpin genes

The combination of arsenic, interferon-alpha, and zidovudine restores an “immunocompetent-like” cytokine expression profile in patients with adult T-cell leukemia lymphoma

BACKGROUND: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. RESULTS: Here we assessed Th1/Th2/T(reg) cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a T(reg)/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4(+)CD25(+) cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4(+)CD25(+) cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. CONCLUSIONS: The observed shift from a T(reg)/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections

La chromatographie de pseudo-bio-affinite. Utilisation d'un ligand general "Histidine" pour la purification et la depyrogenation du facteur anti-hemophilique A du plasma humain

SIGLEINIST T 76027 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc