[Factors associated with poor blood pressure control in Moroccan hypertensive patients]. / Facteurs associés à un mauvais contrôle tensionnel chez les patients hypertendus marocains.

STUDY AIM: Hypertension is a major public health concern worldwide and non-controlling it can lead to various cardiovascular complications. Controlling blood pressure and reducing overall cardiovascular risk are two main goals of treatment. Thus, this study aimed to determine the proportion and factors associated with uncontrolled hypertension in hypertensive patients living in the Beni Mellal city. PATIENTS AND METHODS: The cross-sectional survey took place between June and March 2019. It involved 580 hypertensive patients attending the primary health care facilities in Beni Mellal city, using systematic sampling. RESULTS: A total of 580 hypertensive patients were recruited, with a mean age of 55.78 (± 10.82 years) and of which 66.89% were female. The proportion of poor blood pressure control was 74.1% and was associated in multivariate analysis with a family history of hypertension(OR = 1.60; 95% CI = [1.02-2.50]), dyslipidemia (OR = 2.05; 95% CI = [1.32 -3.20]), non-adherence to a regular BP measurement (OR = 4.13; 95% CI = [2.49 -6.86]), to treatment (OR = 3.64; 95% CI = [2.34-5.65]) and regular biological monitoring (OR = 2.45; 95% CI = [1.46-4.08]). CONCLUSION: Despite the free and available of treatment, the proportion of uncontrolled hypertension was high. This might be linked to a lack of awareness and education concerning disease self-management.

Comparison of PCR and Conventional Serological Methods for Detection of Brucella spp. in Ovine and Caprine Blood Serum.

Brucellosis is an anthropozoonotic disease. Infection of livestock with Brucella is endemic in most parts of Iran. Sistan-Baluchestan is bordered on the east by the countries of Afghanistan and Pakistan. The high prevalence of brucellosis in livestock in the eastern neighboring countries results in transmission of the disease to this province. The present research aimed to determine the prevalence of brucellosis in small ruminants in the Sistan region of Iran and to compare serological and molecular tests for the detection of brucellosis. Blood samples were taken from 150 randomly selected sheep and goats, and sera were separated. All sera were analyzed by serological (Wright and 2-ME) and molecular (Polymerase Chain Reaction (PCR)) tests. Serological tests were carried out according to the instructions of the Iranian Veterinary Organization The degree of agreement between serological tests and PCR was determined by kappa value. In this study, 17 cases (11.3%) were identified as positive by the PCR method. Wright and 2-ME tests had the highest agreement with PCR in titers ≥2/80 and ≥2/40, respectively. The results of this study show that the brucellosis in sheep and goats has a greater prevalence in the Sistan region than in most other parts of Iran, and this is important in terms of public health. It is suggested that brucellosis vaccination coverage in livestock be increased in this area and that the people in Sistan region must be notified about methods for preventing brucellosis. Also, further studies to compare conventional serologic tests with the gold standard test are recommended.

Prevalence and related factors of Salmonella spp. and Salmonella Typhimurium contamination among broiler farms in Kerman province, Iran.

Salmonella is one of the most important pathogens in the poultry industry that not only causes financial and economic damage, but also, some serovars of this bacterium, including the S. Typhimurium, can infect humans through poultry-to-human transmission. The purpose of this study was to investigate the prevalence of this pathogen among broiler poultry houses in the Kerman region, southeast of Iran and to identify factors which could increase the risk for Salmonella contamination in the chickens. In a cross-sectional study, 110 poultry houses were surveyed from June to October 2018. Twenty-eight variables related to the prevalence of Salmonella contamination were considered by a questionnaire template with farmers' and laborers' help. Also, the prevalence of Salmonella in poultry manure was determined based on fecal sampling, microbiological tests and polymerase chain reaction (PCR) technique. A multivariable logistic regression model was developed to measure the influence of independent variables on Salmonella contamination. Results showed that a time interval less than one month between the two breeding periods (OR = 6.530), the number of fans less than 5 in each poultry house (OR = 4.094) and the number of houses less than 4 in each farm significantly increased the probability of infection with Salmonella spp. (ORs were respectively 9.650, 29.427 and 7.140 for one, two and three houses). Also, the results of multivariable logistic regression showed that the use of a bell drinking system (OR = 4.379) and the presence of fewer than 5 fans in each poultry house (OR = 2.512) increased significantly the risk of infection with Salmonella Typhimurium.

A Study on Mycoplasma agalactiae and Chlamydophila abortus in Aborted Ovine Fetuses in Sistan and Baluchestan region, Iran.

Abortion is one of the most important economic issues in sheep flocks. Chlamydophila abortus is an agent of enzootic abortions in sheep. Mycoplasma agalactiae is the main etiological agent of contagious agalactia, which can cause abortion in sheep. The aim of this study was to investigate the prevalence of M. agalactiae and C. abortus among aborted ovine fetuses in Sistan and Baluchestan, Iran. Sheep owners were asked to transfer their aborted fetuses to a nearby veterinary clinic; furthermore, they were taught biosecurity principles. A total of 78 aborted sheep fetuses were collected from all over Sistan region in the autumn of 2015 and winter of 2016. The samples were then transferred in ice to the Anatomy Laboratory of the Veterinary Faculty of Zabol University, Zabol, Iran. The spleen and abomasum contents of the fetuses were sampled under sterile and safe conditions. Polymerase chain reaction was used to detect M. agalactiae and C. abortus. The results showed that 24 (30.8%) cases were infected with M. agalactiae. However, infection with C. abortus was not detected in any fetuses. There was no statistically significant relationship between such independent variables as the location of livestock, history of abortion, fetal gender and age, age and parity of ewe, and fetal infection with M. agalactiae. The high incidence of Mycoplasma contamination in this study may be due to inappropriate biosecurity measures and lack of vaccination against agalactia in sheep herds in Sistan region.

Anthropometric status and body image perception among Moroccan university students.

BACKGROUND: University students aged between 18 and 25 undergo several physical changes as a result of transition from adolescence to adulthood. Students do not always accept those changes and sometimes develop dissatisfaction towards their figures. In such cases, it is still not clear how actual body weight status can be affected by socio-cultural factors such as body image perception. The objective of this study was to determine the link between anthropometric status and body image perception among university students. METHODS: Two hundred and forty six (246) university students from the Faculty of Sciences and Technologies within the Beni Mellal-Khenifra region in Morocco, aged 20-24 years were interviewed using face-to-face questionnaires. Anthropometric measurements and Body Mass Index were collected. Body image perception was assessed by Figure Rating Scale, and body size dissatisfaction was calculated as Feel minus Ideal Discrepancy (FID). Data were described using means and proportions. The Student t-test and the chi-square test have been used to assess the statistical significance of group differences. RESULTS: Underweight students represented 16.7% of the investigated sample, while 11.4% suffered from overweight and obesity, higher in females students (14.4%) than in males (7.9%). Regarding body image perception, 43.9% of participants considered themselves underweight; whereas only 4.2% considered themselves overweight with no significant differences related to gender. Of note, the total prevalence of body image dissatisfaction was around 69.8%. Finally, among overweight/obese students, 88.9% of females and 71.4% of males expressed the wish to become thinner while 28.6% of the overweight/obese males wanted to get heavier. CONCLUSION: The results of this study indicate a high rate of body image dissatisfaction and a tendency of participants to underestimate their body weight. This behavior may be a reflection of a real influence of social and psychological factors occurring during this critical period and may make university students vulnerable to many risk-taking behaviors. Thus, there is a need for suitable interventional programs and innovative strategies to ensure the understanding of the health consequences of overweight and obesity and to prevent associated comorbidities.

Molecular detection of Brucella melitensis, Coxiella burnetii and Salmonella abortusovis in aborted fetuses of Baluchi sheep in Sistan region, south-eastern Iran.

Abortion in sheep and goats causes enormous economic losses. This study revealed the epidemiology of abortion caused by Brucella melitensis, Coxiella burnetii and Salmonella abortusovis in Baluchi sheep in Sistan region. In the autumn of 2015 and winter of 2016, a total of 78 aborted sheep fetuses were collected from all over the Sistan region. Risk factors, including location of livestock, history of abortion, gender of fetus, age of fetus, age of ewe and parity were obtained using a questionnaire. The results showed that 27 fetuses (35%) were infected with these organisms. Infection with B. melitensis, C. burnetii and S. abortusovis were identified respectively in 15 (19.2%), 13 (16.6%) and 1 (1.3%) fetus. Logistic regression analysis showed that infection with B. melitensis in male fetuses is higher than females (OR=3.73, P=0.040), also infection with C. burnetii in ≤2 years' ewes (OR=0.047, P=0.009) and 2-5 years' ewes (OR=0.197, P=0.069) is lower than ≥5 years' ewes.

Current immunogenetic predisposition to tuberculosis in the Moroccan population.

Tuberculosis (TB) is a serious infectious disease that kills approximately two million people per year, particularly in low- and middle-income countries. Numerous genetic epidemiology studies have been conducted of many ethnic groups worldwide and have highlighted the critical impact of the genetic environment on TB distribution. Many candidate genes associated with resistance or susceptibility to TB have been identified. In Morocco, where TB is still a major public health problem, various observations of clinical, microbiological and incidence distribution are heavily affected by genetic background and external environment. Morocco has almost the same clinical profile as do other North African countries, mainly the increase in more extrapulmonary than pulmonary forms of the diseases, when compared to European, Asian or American populations. In addition, a linkage analysis study that examined Moroccan TB patients identified a unique chromosome region that had a strong association with the risk of contracting TB. Other genes in the Moroccan population that were found to be associated seem to be involved predominantly in modulating the innate immunity. In this review, we appraise the major candidate genes that have been reported in Moroccan immunogenetic studies and discuss their updated role in TB, particularly during the first phase of the immune response to Mycobacterium tuberculosis (Mtb) infection.

Cyclosporine A disposition, hepatic and renal tolerance in Wistar rat.

Cyclosporine A, a potent calcineurin inhibitor, has been widely used in organ transplantation and in the treatment of autoimmune diseases. It has, however, been shown to induce serious renal and hepatic side effects. The drug is also used in preclinical studies, but with little published information on the optimal dose and route of administration in rodents. Objectives of this study were to identify efficient and safe doses of cyclosporine A in rodent and to assess its effects on hepatic and renal functions. For this purpose, we tested the effects of different doses and administration routes of cyclosporine A (5, 2.5 and 1 mg/kg) administered during 28 days intraperitoneally, or by gastric feeding on Wistar rats. Our data indicate that rats injected intraperitoneally with 5 mg/kg/2d (every two days) exhibited trough cyclosporine A levels within known therapeutic range in human, but were subject to blood cyclosporine A accumulation, whereas the 5 mg/kg/d gavage resulted in only a small cyclosporine A accumulation over time. In both cases this accumulation was not deleterious to renal and hepatic functions, as shown by transaminase, urea, creatinine and bilirubin measurements.

Syncoilin is an intermediate filament protein in activated hepatic stellate cells.

Hepatic stellate cells (HSCs) play an important role in several (patho)physiologic conditions in the liver. In response to chronic injury, HSCs are activated and change from quiescent to myofibroblast-like cells with contractile properties. This shift in phenotype is accompanied by a change in expression of intermediate filament (IF) proteins. HSCs express a broad, but variable spectrum of IF proteins. In muscle, syncoilin was identified as an alpha-dystrobrevin binding protein with sequence homology to IF proteins. We investigated the expression of syncoilin in mouse and human HSCs. Syncoilin expression in isolated and cultured HSCs was studied by qPCR, Western blotting, and fluorescence immunocytochemistry. Syncoilin expression was also evaluated in other primary liver cell types and in in vivo-activated HSCs as well as total liver samples from fibrotic mice and cirrhotic patients. Syncoilin mRNA was present in human and mouse HSCs and was highly expressed in in vitro- and in vivo-activated HSCs. Syncoilin protein was strongly upregulated during in vitro activation of HSCs and undetectable in hepatocytes and liver sinusoidal endothelial cells. Syncoilin mRNA levels were elevated in both CCl4- and common bile duct ligation-treated mice. Syncoilin immunocytochemistry revealed filamentous staining in activated mouse HSCs that partially colocalized with α-smooth muscle actin, ß-actin, desmin, and α-tubulin. We show that in the liver, syncoilin is predominantly expressed by activated HSCs and displays very low-expression levels in other liver cell types, making it a good marker of activated HSCs. During in vitro activation of mouse HSCs, syncoilin is able to form filamentous structures or at least to closely interact with existing cellular filaments.

Hepatocyte transplantation using the domino concept in a child with tetrabiopterin nonresponsive phenylketonuria.

Phenylketonuria is a metabolic disease caused by phenylalanine hydroxylase deficiency. Treatment is based on a strict natural protein-restricted diet that is associated with the risk of malnutrition and severe psychosocial burden. Oral administration of tetrahydrobiopterin can increase residual enzyme activity, but most patients with severe clinical phenotypes are nonresponders. We performed liver cell transplantation in a 6-year-old boy with severe tetrahydrobiopterin nonresponsive phenylketonuria who failed to comply with diet prescriptions. The transplanted hepatocytes were obtained in part from an explanted glycogen storage type 1b liver. Following two infusions, blood phenylalanine levels returned within the therapeutic target while the phenylalanine half-life assessed by loading tests decreased from 43 to 19 h. However, 3 months later, blood phenylalanine concentrations increased and the phenylalanine intake had to be reduced. Cell-based therapy is a promising therapeutic option in phenylketonuria, and the domino concept may solve the issue of cell sources for hepatocyte transplantation.

Neurogenesis inhibition in the dorsal vagal complex by chronic immobilization stress in the adult rat.

The dorsal vagal complex (DVC) is the brainstem integrative center that mediates the satiety reflex and relays autonomic neural responses to stress. The DVC displays adult neurogenesis, intrinsic neural stem cells and a high brain-derived neurotrophic factor (BDNF) content, effectors of plasticity that are modulated by stress in the hippocampus. In this study we asked whether neurogenesis and BDNF expression in the DVC are altered by stress, in parallel with food intake reduction. To this end, neurogenesis was assessed in adult rats in vivo by repetitive 5-bromo-2'-deoxyuridine (BrdU) administration without (controls) or with daily sessions of immobilization stress (1 h/day), and were allowed to survive for 2 weeks after the end of BrdU treatment. Neurogenic proliferation in the brainstem was detected by immunohistochemistry and confocal microscopy mainly in the area postrema and the nucleus tractus solitarius; newly formed neurons amounted to about 35% of all BrdU-labeled cells in the DVC of control rats. Chronic immobilization stress induced a significant decrease in neurogenic proliferation in the DVC which reached 50% in the area postrema. The number of newly-formed neurons was also decreased by chronic immobilization stress in the DVC, and this effect was again maximal in the area postrema; the proportion of BrdU-labeled cells that were neurons was unchanged. In vitro neurosphere assay was then performed on microdissected DVC tissue from another cohort of chronically stressed and control rats. Chronic immobilization stress induced a significant decrease of the total neurosphere number per rat DVC in both primary and secondary cultures, indicating that intrinsic neural stem cell frequency was decreased by chronic stress in DVC tissue. Tissue BDNF concentration in the DVC, as assessed by enzyme-linked immunosorbent assay, was not significantly altered when compared with controls after 3, 6, 9 or 13 days of chronic immobilization stress. These results further characterize neurogenesis in the DVC and suggest its involvement in the long-term regulation of food intake.

Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside?

There has been recent progress in the isolation and characterisation of stem/progenitor cells that may differentiate towards the hepatic lineage. This has raised expectations that therapy of genetic or acquired liver disease might be possible by transplanting stem/progenitor cells or their liver-committed progeny. However, it is currently impossible to determine from the many documented studies which of the stem/progenitor cell populations are the best for therapy of a given disease. This is largely because of the great variability in methods used to characterise cells and their differentiation ability, variability in transplantation models and inconsistent methods to determine the effect of cell grafting in vivo. This manuscript represents a first proposal, created by a group of investigators ranging from basic biologists to clinical hepatologists. It aims to define standardised methods to assess stem/progenitor cells or their hepatic lineage-committed progeny that could be used for cell therapy in liver disease. Furthermore standardisation is suggested both for preclinical animal models to evaluate the ability of such cells to repopulate the liver functionally, and for the ongoing clinical trials using mature hepatocytes. Only when these measures have been put in place will the promise of stem/progenitor-derived hepatocyte-based therapies become reality.

Present and future applications of hepatic cell transplantation

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Persistence of a chimerical phenotype after hepatocyte differentiation of human bone marrow mesenchymal stem cells.

OBJECTIVES: Recent studies have suggested the potential of mesenchymal stem cells (MSCs) to differentiate into a hepatocyte-like lineage. Here, we evaluate the efficacy of hepatocyte differentiation of MSCs by studying acquisition of hepatocyte-like features together with alteration of the native mesenchymal phenotype. MATERIAL AND METHODS: In vitro, we have investigated protein and mRNA level expression of hepatocyte and mesenchymal markers of mesenchymal-derived hepatocyte-like cells (MDHLCs) and we have evaluated their functionality using metabolic assays. In vivo, we investigated co-expression of hepatocyte (albumin, alpha-foetoprotein, cytokeratin 18) and mesenchymal (fibronectin, vimentin) markers after transplantation of MSCs or MDHLCs into severe combined immune deficiency mice. RESULTS: We observed that while in vitro these cells acquired some phenotypic and functional features of mature hepatocytes, they partially preserved their mesenchymal phenotype. After intrasplenic transplantation, engrafted MSCs with isolated expression of fibronectin and alpha-foetoprotein were observed. When these cells were injected into the liver, they expressed all analysed markers, confirming the chimaeric co-expression observed in vitro. Conversely, liver-engrafted MDHLCs conserved their hepatocyte-lineage markers but lost their chimaeric phenotype. CONCLUSIONS: Hepatocyte differentiation of MSCs predominantly allows the acquisition of phenotypic hallmarks and provides chimaeric cells that maintain expression of initial lineage markers. However, advanced maturation to the hepatocyte-like phenotype could be obtained in vivo by conditioning MSCs prior to transplantation or by infusing cells into the liver micro-environment.

Cell transplantation in the treatment of liver diseases.

The liver performs multiple functions that are essential for life, the most crucial being its role in the body metabolism. Impairment of this function, because of liver insufficiency, can be partially restored by medical management but OLT remains the ultimate therapeutic treatment. Because not always indicated or available, other alternatives are proposed such as LCT. Compared to OLT, this procedure is less invasive, less expensive, and fully reversible. More than 50 patients have thus far benefited of this technique and are reviewed here. Indications were multiple including inborn errors of metabolism, FHF, acute on chronic diseases, and decompensated end-stage cirrhosis. Documented results were encouraging, especially for metabolic disorders, with medium-term efficacy up to two yr. Related complications were exceptional. On this basis, LCT has entered its phase of clinical application and current indications and protocols are detailed. Ongoing lines of research are discussed, including cell quality, stem cell field, and rejection prevention. Further improvement of the procedure is therefore expected and should lead to broader applications of LCT.

Liver cell transplantation.

Liver cell transplantation is an emerging procedure, consisting of infusing mature adult hepatocytes in the portal system of the recipient. It aims to correct inborn errors of liver metabolism, bridge unstable patients to transplantation, or even allow bridge to recovery in fulminant liver failure. The technique addresses ideally patients with inborn errors of metabolism, unstable but not sick enough for orthotopic transplantation. Best results have so far been obtained in metabolic diseases, such as urea cycle disorders, glycogenosis type I, Crigler Najjar, Refsum disease and factor VII deficiency. Cryopreserved hepatocytes can be used, allowing delay between cell isolation and patient's transplantation. The percentage of engraftment obtained can reach up 10%, with de novo expression of deficient enzyme activity. Better results of engraftment have been obtained in animal studies by different chemical or physical techniques, but not yet applied in humans. Because supply of human cells can be limited, research also aims to obtain transplantable cells from other sources, such as embryonic or adult stem cells, or liver progenitor cells that could be expanded in vitro. Careful progression in this field, and collaboration between centers are mandatory to validate further the technique for wider clinical use.

Modulation Of [35S]-tert-butylbicyclophosphorothionate binding by somatostatin in rat hypothalamus.

1. The present study was designed to assess the effect of the tetradecapeptide somatostatin on the GABA(A) receptor complex in the rat hypothalamus. 2. GABA(A) receptors were labelled with [35S]-tert-butylbicyclophosphorothionate (TBPS), which binds in or near the chloride channel, and binding as assessed by in vitro quantitative autoradiography using a computer-assisted image analysis system. 3. Somatostatin inhibited the binding of [35S]-TBPS to the convulsant site of the hypothalamic GABA(A) receptor complex of rat slide-mounted hypothalamic structures in a concentration-dependent manner with an affinity in the micromolar range (10(-6) to 3 x 10(-6) mol/L). Somatostatin appeared to mimic the effects of the neurosteroid 5alpha-pregnane-3alpha ol-one (5alpha3alphaP), GABA and picrotoxin on [35S]-TBPS binding in the rat hypothalamus in all structures examined. Furthermore, GABA or muscimol (a GABA(A) receptor agonist), when added to the incubation medium, enhanced the capacity of somatostatin to inhibit [35S]-TBPS binding, with an IC50 of 10(-7) mol/L. However, incubation with bicuculline (a GABA(A) receptor antagonist) led to the abolition of the inhibitory effect of somatostatin on [35S]-TBPS specific binding in rat hypothalamus. 4. The present results demonstrate the presence of a modulatory effect of somatostatin on the GABA(A) receptor complex in rat hypothalamic structures. Furthermore, the data suggest that somatostatin allosterically modifies [35S]-TBPS binding through a mechanism similar to that of GABA. Taken together, these results provide evidence for the presence of somatostatin- GABA interactions in rat hypothalamus.

Distribution of delta sleep-inducing peptide in the newborn and infant human hypothalamus: an immunohistochemical study.

The distribution of delta sleep-inducing peptide immunoreactive cell bodies, fibers, and terminal-like structures was investigated in the normal human hypothalamus during the first postnatal year, using immunohistofluorescence and peroxidase anti-peroxidase techniques. Immunolabeled perikarya were relatively few and were mostly scattered through the anterior (preoptic) and mediobasal regions (infundibular nucleus) of the hypothalamus. DSIP-immunoreactive fibers and terminal-like fibers were observed throughout the entire rostrocaudal extent of the hypothalamus. They exhibit high densities in the preoptic region, the organum vasculosum of lamina terminalis, infundibular nucleus and median eminence. Moderate to low densities of DSIP-immunoreactive fibers were observed in the other hypothalamic structures, located in the anterior and mediobasal regions of hypothalamus, such as periventricular, paraventricular, suprachiasmatic, ventromedial, dorsomedial and parafornical nuclei. In the present study, the analysis of the immunohistochemical pattern of DSIP-immunoreactive neuronal elements in the human infant hypothalamus during the first postnatal year provided evidence of the presence of several differences. We have found qualitative age-related changes in the density of DSIP immunoreactivity in several hypothalamic structures such as the anterior region and the median eminence.