The amidated PACAP1-23 fragment is a potent reduced-size neuroprotective agent.

BACKGROUND: Neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by neuronal death involving, among other events, mitochondrial dysfunction and excitotoxicity. Along these lines, several attempts have been made to slow this pathology but none have been yet discovered. Based on its capacity to cross the blood-brain barrier and provide neuronal protection in vitro and in vivo, the pituitary adenylate cyclase-activating polypeptide (PACAP) represents a promising lead molecule. Pharmacological studies showed that PACAP interacts with three different G protein-coupled receptors, i.e. PAC1, VPAC1 and VPAC2. However, only PAC1 is associated with neuronal anti-apoptotic actions, whilst VPAC activation might cause adverse effects. In the context of the development of PAC1-selective agonists, PACAP(1-23) (PACAP23) appears as the shortest known PACAP bioactive fragment. METHODS: Hence, the capacity of this peptide to bind PACAP receptors and protect neuroblastoma cells was evaluated under conditions of mitochondrial dysfunction and glutamate excitotoxicity. In addition, its ability to activate downstream signaling events involving G proteins (Gαs and Gαq), EPAC, and calcium was also assessed. RESULTS: Compared to the endogenous peptide, PACAP23 showed a reduced affinity towards PAC1, although this fragment exerted potent neuroprotection. However, surprisingly, some disparities were observed for PACAP23 signaling compared to full length PACAP, suggesting that downstream signaling related to neuroprotection is distinctly regulated following subtle differences in their PAC1 interactions. CONCLUSIONS: Altogether, this study demonstrates the potent neuroprotective action of amidated PACAP23. GENERAL SIGNIFICANCE: PACAP23 represents an attractive template for development of shorter PACAP-derived neuroprotective molecules.

Epidemiology of viral hepatitis in the Maghreb.

INTRODUCTION: Viral hepatitis represents a serious public health problem in the world especially in the Maghreb where the prevalence of the 5 viruses A, B, C, D, and E remains high and varies from one Maghreb country to another, there is few published studies on these infections in our Maghreb countries. METHOD OF STUDY: Our work is a review of the literature about prevalence, the most common mode of transmission, and the most exposed population for these viruses in the Maghreb countries through published studies between 2011 and 2017. RESULT: It has been found that the Maghreb countries are endemic for the five viruses with variable prevalence from one country to another, with sometimes heterogeneous data in the same country. For hepatitis B, Mauritania is the Maghreb country most affected by this infection unlike the rest of the Maghreb countries which are moderately endemic for this virus, the lowest prevalence of VHB was noted in Morocco, the genotype the most common is the D for the majority of Maghreb countries, and the precore mutant profile is also the most common. For hepatitis C the prevalence of infection does not vary much from one Maghreb country to another, but it remains slightly higher in Mauritania. The population most exposed to the virus C in the five countries is hemodialysis patients. The most common genotype in all Maghreb countries is genotype 1 except for Libya, where genotype 4 remains the most common probably related to its borders with Egypt. For hepatitis D, Mauritania is the only Maghreb country with a high endemicity for the virus. Tunisia has the lowest prevalence for hepatitis A and E compared to the rest of the Maghreb countries, all of which are endemic for these two viruses with fecal-oral transmission. CONCLUSION: The management of these viral hepatitis is costly for the health economy and to reduce their prevalence, prevention measures must be followed like vaccination and improving hygiene conditions.

Impact of electronic-cigarette refill liquid on rat testis.

Electronic cigarettes (e-cigarettes) are becoming the fashionable alternative to decrease tobacco smoking, although their impact on health has not been fully assessed yet. The present study was designed to compare the impact of e-cigarette refill liquid (e-liquid) without nicotine to e-liquid with nicotine on rat testis. For this purpose, e-liquid with nicotine and e-liquid without nicotine (0.5 mg/kg of body weight) were administered to adult male Wistar rats via the intraperitoneally route during four weeks. Results showed that e-liquid with or without nicotine leads to diminished sperm density and viability, such as a decrease in testicular lactate dehydrogenase activity and testosterone level. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified a reduction in cytochrome P450 side-chain cleavage (P450 scc) and 17 beta-hydroxysteroid dehydrogenase (17ßHSD) mRNA level, two key enzymes of steroidogenesis. Following e-liquid exposure, histopathological examination showed alterations in testis tissue marked by germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules. Finally, analysis of oxidative stress status pointed an outbreak of antioxidant enzyme activities such as superoxide dismutase, catalase and gluthatione-S-transferase, as well as an important increase in sulfhydril group content. Taken together, these results indicate that e-liquid per se induces toxicity in Wistar rat testis, similar to e-liquid with nicotine, by disrupting oxidative balance and steroidogenesis.

Interpretation of psychophysics response curves using statistical physics.

Experimental gustatory curves have been fitted for four sugars (sucrose, fructose, glucose and maltitol), using a double layer adsorption model. Three parameters of the model are fitted, namely the number of molecules per site n, the maximum response RM and the concentration at half saturation C1/2. The behaviours of these parameters are discussed in relationship to each molecule's characteristics. Starting from the double layer adsorption model, we determined (in addition) the adsorption energy of each molecule on taste receptor sites. The use of the threshold expression allowed us to gain information about the adsorption occupation rate of a receptor site which fires a minimal response at a gustatory nerve. Finally, by means of this model we could calculate the configurational entropy of the adsorption system, which can describe the order and disorder of the adsorbent surface.

Statistical thermodynamics of adsorption of dye DR75 onto natural materials and its modifications: double-layer model with two adsorption energies.

In this article, adsorption modelling was presented to describe the sorption of textile dye, Direct Red 75 (DR75), from coloured wastewater onto the natural and modified adsorbent, Posidonia oceanica. The formulation of the double-layer model with two energy levels was based on statistical physics and theoretical considerations. Thanks to the grand canonical ensemble in statistical physics some physico-chemical parameters related to the adsorption process were introduced in the analytical model expression. Fitting results show that the dye molecules are adsorbed in parallel position to the adsorbent surface. The magnitudes of the calculated adsorption energies show that the DR75 dye is physisorbed onto Posidonia. Both Van der Waals and hydrogen interactions are implicated in the adsorption process. Despite its simplicity, the model fits a wide range of experimental data, thereby supporting the underlying data that the grafted groups facilitate the parallel anchorage of the anionic dye molecule. Thermodynamic parameters, such as adsorption energy, entropy, Gibbs free adsorption energy and internal energy were calculated according to the double-layer model. Results suggested that the DR75 adsorption onto Posidonia was a spontaneous and exothermic process.

Acid dye adsorption onto cationized polyamide fibres. Modeling and consequent interpretations of model parameter behaviours.

Experimental adsorption isotherms of four acid dyes named Acid Blue 25, Acid Yellow 99, Reactive Yellow 23, and Acid Blue 74 from aqueous solution onto cationized nylon-6,6 have been analyzed using a double layer adsorption model. The parameters involved in the analytical expression of this model such as the number or fraction of adsorbed dye molecule per site, n, the number of receptor sites per gram of adsorbent, N(M), and the concentration at half-saturation, c1/2, are determined from adsorption isotherms at four temperatures between 293 and 353 K. The evolution of these parameters with temperature is discussed in relation with adsorption process and the behaviours of the different dyes taking into account their particular structure. The results are compared with those already published dealing with the adsorption of these same dyes onto cationized cotton. The configurational entropy at various temperatures has been studied. This parameter allowed to deduce some results related to the evolution of the disorder during the adsorption process.

New theoretical expressions for the five adsorption type isotherms classified by BET based on statistical physics treatment.

New theoretical expressions to model the five adsorption isotherm types have been established. Using the grand canonical ensemble in statistical physics, we give an analytical expression to each of five physical adsorption isotherm types classified by Brunauer, Emett, and Teller, often called BET isotherms. The establishment of these expressions is based on statistical physics and theoretical considerations. This method allowed estimation of all the mathematical parameters in the models. The physicochemical parameters intervening in the adsorption process that the models present could be deduced directly from the experimental adsorption isotherms by numerical simulation. We determine the adequate model for each type of isotherm, which fixes by direct numerical simulation the monolayer, multilayer, or condensation character. New equations are discussed and results obtained are verified for experimental data from the literature. The new theoretical expressions that we have proposed, based on statistical physics treatment, are rather powerful to better understand and interpret the various five physical adsorption type isotherms at a microscopic level.

Synthesis and biological evaluation of folate receptor-targeted boronated PAMAM dendrimers as potential agents for neutron capture therapy.

Successful treatment of cancer by boron neutron capture therapy (BNCT) requires the selective delivery of (10)B to constituent cells within a tumor. The expression of the folate receptor is amplified in a variety of human tumors and potentially might serve as a molecular target for BNCT. In the present study we have investigated the possibility of targeting the folate receptor on cancer cells using folic acid conjugates of boronated poly(ethylene glycol) (PEG) containing 3rd generation polyamidoamine dendrimers to obtain (10)B concentrations necessary for BNCT by reducing the uptake of these conjugates by the reticuloendothelial system. First we covalently attached 12-15 decaborate clusters to 3rd generation polyamidoamine dendrimers. Varying quantities of PEG units with varying chain lengths were then linked to these boronated dendrimers to reduce hepatic uptake. Among all prepared combinations, boronated dendrimers with 1-1.5 PEG(2000) units exhibited the lowest hepatic uptake in C57BL/6 mice (7.2-7.7% injected dose (ID)/g liver). Thus, two folate receptor-targeted boronated 3rd generation polyamidoamine dendrimers were prepared, one containing approximately 15 decaborate clusters and approximately 1 PEG(2000) unit with folic acid attached to the distal end, the other containing approximately 13 decaborate clusters, approximately 1 PEG(2000) unit, and approximately 1 PEG(800) unit with folic acid attached to the distal end. In vitro studies using folate receptor (+) KB cells demonstrated receptor-dependent uptake of the latter conjugate. Biodistribution studies with this conjugate in C57BL/6 mice bearing folate receptor (+) murine 24JK-FBP sarcomas resulted in selective tumor uptake (6.0% ID/g tumor), but also high hepatic (38.8% ID/g) and renal (62.8% ID/g) uptake, indicating that attachment of a second PEG unit and/or folic acid may adversely affect the pharmacodynamics of this conjugate.

[Chondrosarcoma of the hand. Diagnostic and therapeutic discussion (three case reports)]. / Le chondrosarcome de la main. Discussion diagnostique et thérapeutique (à propos de trois cas).

Chondrosarcoma of the hand is very rare. We report three observations which enable us to make a review of its pathology. There were two men and one woman aged 72, 38 and 63 years respectively. Localisation was phalangeal in two cases and metacarpal in one case. Two cases were central and one peripheral. Radiographs were characterised by the presence of lytic areas with intralesional calcifications and soft tissue extension. Histological diagnosis was made by biopsy in two cases and after amputation of the finger for lesional spread in one case. Treatment consisted of amputation of the finger in two cases. In the case of metacarpal localisation, wide resection of two rays was followed by recurrence after ten months which required amputation of the hand. We agree with other authors who believe that chondrosarcoma in the hand is due to malignant change in a pre-existing chondroma. Conservative treatment is difficult due to the small size of the hand which allows easy spread of the tumour from compartment to compartment.

[Solitary osteochondroma of the limbs. Clinical review of 76 cases and pathogenic hypothesis]. / L'exostose ostéogénique solitaire des membres. Revue clinique de 76 cas et hypothèse pathogénique.

The authors report a retrospective study of 76 solitary osteochondromas of the appendicular skeleton treated between 1981 and 1995. The ages of the patients ranged from 13 to 55 years with a mean of 21 years. The male/female-ratio was 1.37. Tumefaction with or without associated pain was the reason for consultation in 68 cases (89%). In 62 cases the osteochondroma was localized in the distal part of the femur or the proximal part of the tibia. All lesions were surgically resected; the resection was complete in all cases. Six patients were lost to follow-up; the other 70 were seen on a regular basis over a time period ranging from 1 to 12 years. The result from surgical treatment was assessed based on pain, joint motion, cosmetic consequences, nerve compression and recurrence of osteochondroma. The results were good in 68 cases and fair in two cases. Based on a review of previous experimental studies, the authors suggest a hypothesis to explain the rotation of a fragment of the growth plate which is needed for the development of osteochondroma. This rotation occurs as a result of the mechanical action from the periosteum under tension.

Application of statistical thermodynamics to the olfaction mechanism.

The application of the grand canonical ensemble in statistical thermodynamics to the stimulus adsorption on the olfactory receptor sites, assuming some simplifying hypotheses, leads us to an expression of the olfactory response R, which is a function of various physico-chemical parameters involved in the olfaction mechanism, e.g. the stimulus concentration, the saturated vapor pressure, the power law exponent and the partition coefficient. This expression of R is in agreement with the olfactory response of the Hill model, but is more explicit. Stevens' law and the olfactory threshold expression are easily deduced from R. The expression of the threshold we established from R enabled us to explain some empirical relations in the literature between the parameters quoted above. The use of the grand canonical ensemble with the chemical potential notion gave us an interpretation of Stevens' law and a better understanding of the role of some parameters involved in the olfaction mechanism, such as saturated vapor pressure and power law exponent.

Tuberculous osteitis in limbs. Twenty five case-reports.

Tuberculous osteitis is a rare condition that can be difficult to differentiate from bone tumor on X-ray films. The purpose of this retrospective study was to analyse the epidemiologic, diagnostic and therapeutic aspects of this disorder. Data from 25 patients (13 men; 12 women; mean age = 37) were collected between 1984 and 1993. The source of contagion was traced in 32% of the cases and 24% of patients were known as tuberculous. Patients searched medical attention because of pain in 84% of cases. The greater trochanter was involved in more than 50% of cases. The definite diagnosis was obtained by examination of a surgical biopsy and the anti-bacillary treatment led to recovery in all cases. This study highlights that tuberculosis must be considered when investigating a bone lacuna, all the more so when the greater trochanter is involved, in a country where tuberculosis is endemic.

[Isolated tuberculosis of popliteal cyst. Apropos of a case]. / La tuberculose isolée du kyste poplité. A propos d'un cas.

INTRODUCTION: Isolated localization of tuberculosis in the popliteal cyst is an exceptional affection. CASE REPORT: Mr. M.L., 18-year-old black moroccan, was admitted for a painful swelling of the left popliteal cyst, general state alteration and left thoracic pain. Clinical examination found a 5 cm on 3 cm oval tumefaction at the supero-medial part of the left popliteal hollow. No articular effusion was noted. Left knee X ray was normal, while ultrasound examination showed a modified popliteal cyst. Chest X ray showed a pleural effusion. Tuberculine skin test was positive (18 mm). A subtotal resection of the cyst was performed, evacuating 10 ml of thick pus. The histologic examination of the cyst confirmed its tuberculosis origin. In addition the left pleural biopsy confirmed the diagnosis of tuberculosis as well. The antibacillar treatment based on rifampicine, INH and pyrazinamide was given during 6 months. The evolution was favorable at 2 years of follow-up. DISCUSSION: Knee popliteal cyst is frequently an expression of an inflammatory or traumatic affection. The communication between the articular synovium and the serosa bursa of the lateral gastrocnemius is found in 50 per cent of cases, allowing an association of both localizations of tuberculosis. Hamabuchi described for the first time an isolated popliteal cyst tuberculosis in 1990. This case is similar to Hamabuchi's observation. Clinical and radiographical examinations were normal thus excluding a possible dissemination from the knee joint.

[Multifocal bone tuberculosis: apropos of a case]. / La tuberculose osseuse multifocale: à propos d'un cas.

INTRODUCTION: Tuberculosis of bone is rare (10 to 20 per cent of all skeletal tuberculosis). The multifocal form is exceptional even in endemic countries of tuberculosis. It constitutes less than 5 per cent of all osseous tuberculosis. CASE REPORT: O.H. 34 year-old, Moroccan woman of black race not vaccinated against tuberculosis, with a contagion, complained for a year from scapular pain and weight loss. She noticed that two masses had appeared six months ago. The patient was feverish (38 degrees). The physical exam showed a non inflammatory mass 10 cm wide located in front of the left sacroiliac joint and seeming to be a cold abscess. The radiologic assessment showed a lytic image of the humerus upper extremity, the right iliopubis branch, the left ischium and the left iliac wing. The surgical biopsy of the humerus showed an evolutive caseo-follicular tuberculosis. The nuclear scan of bone found two other localizations in the fourth lumbar vertebra and the ninth left rib. We concluded to a multifocal bone tuberculosis with seven localizations: The upper extremity of both humerus Right pubis Left ischium Left iliac wing 4th lumbar vertebra 9th left rib. The treatment consisted in a specific antibiotic therapy for 6 months associated to the evacuation of the cold abscess. DISCUSSION: Multifocal bone tuberculosis is more frequent in young adults of black race. The beginning of the disease is progressive and the fistulas are the main reason of consultation. The radiologic lesions are not specific and have a geodic shape rimmed with an osteocondensation. Multifocal bone tuberculosis in black african predominate in flat bones. Otherwise in the white race it is located in the long bones extremities. The diagnosis of certitude is based on histologic findings of the peripheric bone lesion. The specific antibiotic therapy leads to the recovery if given early. Short protocols (9 or 6 months) are recently more used with success.

[Carpal perilunar dislocation. Clinical study (apropos of 39 cases)]. / Luxations péri-lunaires du carpe. Etude clinique (à propos de 39 cas).

Carpal perilunar dislocations are hidden lesions with uncertain outcome and treatment which is not yet standardized. This retrospective study including 39 cases of carpal perilunar dislocations helps clarify these issues. For fresh dislocations, the diagnosis was established in 66%. Surgical treatment was performed in 26 cases. Anatomic results showed nonunion, necrosis and residual instability. Function was always decreased and was worse in open forms or after orthopedic treatment. Scaphoid screwing results were better than those from pinning. Lateral wrist x rays must always be ordered in cases of wrist trauma to avoid delayed diagnosis. Surgical treatment must systematically use a palmar incision; it permits precise repair of bones and ligamentous lesions and reduces the risk of arthritis.

[Idiopathic acro-osteolysis. Apropos of a case with carpal-tarsal onset]. / L'acro-ostéolyse idiopathique. A propos d'un cas à début carpo-tarsien.

This work reports an isolated case of idiopathic acro-osteolysis with a carpo-tarsian onset without associated nephropathy, diagnosed in a 16 year-old patient. It has raised problems of etiologic diagnosis, of classification and therapeutic behaviour in the presence of destructive lesions with an extensive and progressive evolution.

[Arthrolysis of the elbow--apropos of 70 cases]. / L'arthrolyse du coude--à propos de 70 cas.

This retrospective review covers 70 cases of elbow stiffness treated by arthrolysis. The average age was 27 years. Eighty percent had a posttraumatic origin; 53.6% were old dislocations. In 67.1% the range of movement was reduced for flexion and extension; 80% were severe to very severe cases. Physiotherapy was passive and active from the third postoperative day, except for the old dislocations, treated for 2 weeks by fixation of the radial condyle, because of instability. For 51.4% the range of movement was -30 degrees extension up to 130 degrees flexion, intra-operatively; for 21.4% it was a long-term result. The results were related to the damage to the joint space, the large number of old dislocations and insufficient rehabilitation.

[Preventive treatment of hemodynamic disorders during conventional spinal anesthesia]. / Traitement préventif des perturbations hémodynamiques au cours de la rachianesthésie conventionannelle.

The prevention of blood pressure fall during a conventional spinal anaesthesia effected with 20 mg (4 ml) of isobaric 0.5 p. 100 bupivacaine relies on the use of vascular filling and/or a vasoconstrictor. A randomized prospective study was performed to evaluate the comparative efficacy of these two treatments. 148 patients were included and divided into three groups. Group I (n = 50): 2.5 mg IV bolus of etilefrine followed by continuous infusion (0.35 mg.kg-1.h-1). Group II (n = 50): 30 ml.kg-1 infusion of saline isotonic solution for 90 min, with infusion rate according to blood pressure. Group III (n = 48) did not receive any preventive treatment. A blood pressure fall of more than 30% of the initial value was observed in 59 patients: 18% of the etilefrine group, 28% of the saline infusion group, 54% of the control group. This peculiar frequency of hypotension in the control group emphasizes the need of a preventive treatment. Haemodynamic changes were fewer and less important in the etilefrine group compared with the saline infusion group. No failure and a better tolerance in the vasoconstrictor group were also to be noticed. These clinical data suggest that etilefrine could meet satisfactorily the therapeutic requirements.

[An osteoid osteoma of the os capitatum]. / L'ostéome ostéoïde du grand os.

We report a hyperalgic form of an osteoid osteoma of the capitatum, wich had evolved since 14 months. The diagnosis was done by roentgenography. Complete surgical excision of the lesion led to the cure.