Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug

The cholinergic anti-inflammatory pathway is one of the putative biochemical pathways that link diabetes with Alzheimer disease. Hence, we aimed to verify the potential antidiabetic effect of galantamine, unveil the possible mechanisms and evaluate its interaction with vildagliptin. The n5-STZ rat model was adopted and the diabetic animals were treated with galantamine and/or vildagliptin for 4 weeks. Galantamine lowered the n5-STZ-induced elevation in body weight, food/water intake, serum levels of glucose, fructosamine, and ALT/AST, as well as AChE in the tested organs. Moreover, it modulated successfully the lipid profile assessed in serum, liver, and muscle, and increased serum insulin level, as well as % β-cell function, in a pattern similar to that of vildagliptin. Additionally, galantamine confirmed its antioxidant (Nrf2, TAC, MDA), anti-inflammatory (NF-κB, TNF-α, visfatin, adiponectin) and anti-apoptotic (caspase-3, cytochrome c) capabilities by altering the n5-STZ effect on all the aforementioned parameters. On the molecular level, galantamine/vildagliptin have improved the insulin (p-insulin receptor, p-Akt, GLUT4/GLUT2) and Wnt/β-catenin (p-GSK-3β, β-catenin) signaling pathways. On almost all parameters, the galantamine effects surpassed that of vildagliptin, while the combination regimen showed the best effects. The present results clearly proved that galantamine modulated glucose/lipid profile possibly through its anti-oxidant, -apoptotic, -inflammatory and -cholinesterase properties. These effects could be attributed partly to the enhancement of insulin and Wnt/β-catenin signaling pathways. Galantamine can be strongly considered as a potential antidiabetic agent and as an add-on therapy with other oral antidiabetics.     

Optimization of pectin extraction from lemon by-product with acidified date juice using response surface methodology

Response surface methodology was used to optimize pectin recovery from lemon by-product using an acidified date juice as extraction solution. When enriched in pectin, this latter can be useful for preparation of date-lemon jelly. The effects of three parameters namely temperature, pH and extraction time, on pectin extraction were studied. The fitted mathematical model allowed us to plot response surfaces as well as isoresponse curves and to determine optimal extraction conditions. Results clearly indicated that the temperature was the main factor influencing the pectin yield which increased with temperature and time or decreasing pH. The selected optimal conditions were: temperature 84.34 °C; extraction time 3 h 34 min and pH 2.8. These conditions yielded about 11.21% of pectin versus 10.89% for the predicted value.     

Aspects cliniques et biologiques de l’azoospermie chez l’homme infertile en Tunisie

Objective

It is now very important to investigate azoospermia because the introduction of the intracytoplasmic sperm injection technique during the last decade has allowed many infertile men to achieve their dreams of fatherhood. The purpose of this study was to define the characteristics of infertile men with azoospermia, and to analyse the clinical and laboratory features and the causes of infertility in Tunisia. The authors also discuss various aspects that they consider to be very important in the diagnosis of male fertility.

Material and Methods

This retrospective study analysed the parameters of physical examination, laboratory tests, semen analysis, radiographic examinations, testicular biopsy, karyotype and AZF microdeletions.

Results

Based on the results of endocrinological and cytogenetic examinations, the aetiology of azoospermia was considered to be secretory in 43 cases of azoospermia. Physical examination revealed a high percentage of hypotrophic/atrophic testes (43.9%). Serum follicle stimulating hormone levels were high in 58.5% of cases. The overall incidence of chromosomal abnormalities was 31.4%. The most frequent anomaly was Klinefelter syndrome (9 cases). Seven out of 28 patients (25%) with nonobstructive azoospermia had AZF deletions. None of the patients with excretory azoospermia and severe oligospermia had an abnormal karyotype or AZF microdeletions. 48.8% of patients presented a varicocele, 13.9% had cryptorchidism and 13.0% had a history of genital tract infection.

Conclusion

In line with the literature, genetic abmormalities are the main causes of severe forms of impaired spermatogenesis in the Tunisian population.     

Menaquinone biosynthesis potentiates haem toxicity in Staphylococcus aureus

Staphylococcus aureus is a pathogen that infects multiple anatomical sites leading to a diverse array of diseases. Although vertebrates can restrict the growth of invading pathogens by sequestering iron within haem, S. aureus surmounts this challenge by employing high‐affinity haem uptake systems. However, the presence of excess haem is highly toxic, necessitating tight regulation of haem levels. To overcome haem stress, S. aureus expresses the detoxification system HrtAB. In this work, a transposon screen was performed in the background of a haem‐susceptible, HrtAB‐deficient S. aureus strain to identify the substrate transported by this putative pump and the source of haem toxicity. While a recent report indicates that HrtAB exports haem itself, the haem‐resistant mutants uncovered by the transposon selection enabled us to elucidate the cellular factors contributing to haem toxicity. All mutants identified in this screen inactivated the menaquinone (MK) biosynthesis pathway. Deletion of the final steps of this pathway revealed that quinone molecules localizing to the cell membrane potentiate haem‐associated superoxide production and subsequent oxidative damage. These data suggest a model in which membrane‐associated haem and quinone molecules form a redox cycle that continuously generates semiquinones and reduced haem, both of which react with atmospheric oxygen to produce superoxide.     

Mutational analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in Tunisian patients with nonsyndromic hearing loss

We explored the mitochondrial 12S rRNA and the tRNASer(UCN) genes in 100 Tunisian families affected with NSHL and in 100 control individuals. We identified the mitochondrial A1555G mutation in one out of these 100 families and not in the 100 control individuals. Members of this family harbouring the A1555G mutation showed phenotypic heterogeneity which could be explained by an eventual nuclear-mitochondrial interaction. So, we have screened three nuclear genes: GJB2, GJB3, and GJB6 but we have not found correlation between the phenotypic heterogeneity and variants detected in these genes. We explored also the entire mitochondrial 12S rRNA and the tRNASer(UCN) genes. We detected five novel polymorphisms: T742C, T794A, A813G, C868T, and C954T, and 12 known polymorphisms in the mitochondrial 12S rRNA gene. None of the 100 families or the 100 controls were found to carry mutations in the tRNASer(UCN) gene. We report here the first mutational screening of the mitochondrial 12S rRNA and the tRNASer(UCN) genes in the Tunisian population which describes the second family harbouring the A1555G mutation in Africa and reveals novel polymorphisms in the mitochondrial 12S rRNA gene.     

Lipid Peroxidation and Antioxidant System in the Tumor and in the Blood of Patients with Nasopharyngeal Carcinoma

Reactive oxygen species play a key role in cancer development by inducing and maintaining the oncogenic phenotypes of cancer cells. In this study, we examined lipid peroxidation and antioxidant enzymes activities in the blood and in the tumor of nasopharyngeal carcinoma patients. Plasma malondialdehyde, conjugated dienes, erythrocytes catalase, and superoxide dismutase activities have been measured in 30 untreated nasopharyngeal carcinoma patients and 30 controls on one hand. On the other hand, tumor malondialdehyde level, catalase, and superoxide dismutase activities have been measured in five nasopharyngeal carcinoma patients and compared with four controls. The lipid peroxidation was confirmed in the plasma by the high levels of malondialdehyde and conjugated dienes (p?<?0.001, respectively). Additionally, significantly higher concentrations of malondialdehyde were found in biopsies compared to the control group (p?<?0.001). In erythrocytes, superoxide dismutase activity was higher in patients than in controls (p?<?0.05), while it was unchanged in the tumor (p?>?0.05). Both erythrocytes and tumor catalase activities were significantly lower in patients than in controls (p?<?0.001, respectively). Statistical studies have shown a positive correlation between malondialdehyde level and IgA antibodies level against Epstein–Barr virus capsid antigen (p?<?0.05). In conclusion, we reported the presence of an oxidative stress in the blood and in the biopsies of nasopharyngeal carcinoma patients where Epstein–Barr virus seems to play a role.     

Whole inedible date in the grower-finisher broiler diets and the impact on productive performance, nutrient digestibility and meat quality

The growth performance, carcass characteristics and meat quality measurements were evaluated on broiler chicks fed different dietary levels of whole inedible dates (WID). WID used in this study were consisted of date fruits (～850 g/kg) and date pits (～150 g/kg). Three hundred unsexed Lohman broiler chicks were randomly and equally distributed into six groups. Each was formed of 50 chicks (five replicates, 10 chicks per replicate), and was assigned to a dietary treatment. Six dietary treatments of WID (0, 30, 60, 90, 120 and 150 g/kg feed) were included in the formation of isocaloric (metabolizable energy of ～3060 kcal/kg feed) and isonitrogenous (CP of ～192 g/kg feed) broiler rations. The treated rations were fed to the group chicks between 15 and 42 days of age (the experimental period). A straight-run design was considered. At 42 days of age, five males from each treatment were randomly chosen and slaughtered to determine carcass characteristics, internal organs and meat quality measurements. Digestibility of nutrients was measured at the end of the experimental period using five caged-individual males per treatment. The inclusion of broiler rations on WID for up to 150 g/kg feed, over the experimental period, did not significantly influence body weight gain (1452 to 1521 g/chick), feed intake (3268 to 3621 g/chick), feed conversion ratio (2.26 to 2.36 kg/kg) and dressed carcass (63.4% to 67.3%). In addition, levels of WID for up to 150 g/kg feed did not significantly influence the digestibility of nutrients and meat quality measurements. Such results suggest the possible inclusion of broiler rations on WID for up to 150 g/kg feed, during the period of 15 to 42 days of age without adverse effects on growth performance and meat quality.     

Les lésions de l’urètre associées à une fracture des corps caverneux. A propos d’une série de 4 cas et revue de la littérature

Introduction

Urethral injury associated with corpora cavernosa fracture is a relatively uncommon form of urological trauma. Early diagnosis and immediate surgical repair are essential.

Patients and methods

Between January 1990 and December 2004, a total of 4 male patients with urethral injury associated with fracture of the corpora cavernosa were retrospectively studied from a series of 96 cases of penile fracture.

Results

The mean age of the patients was 36.5 years (range: 27–45 years). Urethral bleeding was noted in all patients. Immediate surgical repair via a penile circular subcoronal incision was performed in all cases. Two partial urethral injuries associated with a unilateral corpus cavernosum lesion were identified. In the other cases, total urethral injury was associated with bilateral rupture of the corpora cavernosa. The tunica albuginea defect was closed and the urethral laceration repaired over a urethral catheter. With a mean follow-up of 2.5 years, 2 short urethral strictures were observed and were managed non-operatively with good outcome.

Comments

Secondary urethral lesions associated with corpora cavernosa fracture most frequently affect young adults. In North African countries, forced self-manipulation of an erect penis is the most frequent cause, but the associated urethral lesion is usually related to vaginal intercourse. The diagnosis can generally be made on the basis of history and physical examination alone. Blood at the meatus or haematuria or voiding difficulties suggest associated trauma to the urethra [4]. Additional imaging examinations are rarely required. The standard treatment is prompt surgical exploration, evacuation of haematoma, and primary repair of the urethral and corpora cavernosa defects. Late complications after surgical repair are penile curvature and pain during coitus. They are usually attributable to a residual fibrotic area.

Conclusion

Urethral injury associated with corpora cavernosa fracture usually has typical signs. The mechanism of trauma is very suggestive. Early surgical treatment is the only guarantee of a satisfactory functional result.