Comparative value of prostaglandin E1 and papaverine in treatment of erectile failure: double-blind crossover study among Egyptian patients.

In a double-blind, crossover designation penile intracavernous prostaglandin E1 and papaverine hydrochloride were compared in regard to effectiveness and safety in 52 patients investigated and treated for sexual erectile dysfunction. In evidence of the reliable effectiveness, prostaglandin E1 (20 micrograms/ml.) induced significant positive erectile response in 42 of 52 patients (81%). This rate reached 100% with neurogenic, hyperprolactinemic and/or psychogenic impotence. However, with papaverine hydrochloride (30 mg./ml.) and exclusively in cases of vasculogenic (most probably arteriogenic) impotence, negative erectile response was revealed as absent erection in 6 of 52 patients (11.5%) and nonrigid tumescence in 13 (25%) versus 2 (3.8%) and 8 (15.4%), respectively, with prostaglandin E1. Moreover, with prostaglandin E1 the regional pain was tolerable and transient, and the positive erectile response was not attended by priapism even in patients who formerly had priapism with papaverine hydrochloride. However, presently with prostaglandin E1 the relatively higher cost and shorter expiration period would probably limit its diagnostic and therapeutic use in Egypt, and probably in other developing countries.     

Endotoxin-induced desensitization of mouse macrophages is mediated in part by nitric oxide production.

Refractoriness (tolerance) to endotoxin effects, such as induction of tumor necrosis factor alpha (TNF-alpha) secretion, can be elicited in vitro in macrophages by preexposure of cells to endotoxin (lipopolysaccharide [LPS]) itself. The aim of this study was to determine whether this phenomenon is due to negative feedback mediated by the free radical nitric oxide (NO) produced by cells when they are activated by LPS. Among several efficient inhibitors of NO production, NG-monomethyl-L-arginine did not induce concomitant inhibition of TNF-alpha secretion. Mouse macrophages that were exposed to LPS in the presence of NG-monomethyl-L-arginine partially maintained the ability to secrete TNF-alpha in response to a second LPS stimulation, compared with cells preexposed to LPS alone, thus suggesting that NO is involved in part in LPS-induced desensitization of cells. Furthermore, direct exposure of cells to the NO-generating compounds sodium nitroprusside and S-nitroso-N-acetylpenicillamine mimicked LPS-induced desensitization. However, low concentrations of a synthetic lipid (lipid M4) that is structurally analogous to the reducing end of the lipid A moiety of LPS induced desensitization of mouse macrophages without concomitant production of NO. Taken together, these data suggest that although NO actually takes part in LPS-induced desensitization of mouse macrophages, additional and yet unknown mechanisms must also exist.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

3,4,3′-Tri-O-methylellagic acid as an anticancer agent: in vitro and in silico studies

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3′-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment. The characterization of the isolated T-EA compound was carried out using various spectroscopic methods. The in vitro evaluation showcased the inhibition activity of T-EA towards the T47D and HeLa cell lines with EC₅₀ values of 55.35 ± 6.28 μg mL⁻¹ and 12.57 ± 2.22 μg mL⁻¹, respectively. Meanwhile, the in silico evaluation aimed to understand the interaction of T-EA with enzymes responsible for cancer regulation at the molecular level by targeting the hindrance of cyclin-dependent kinase 9 (CDK9) and sirtuin 1 (SIRT1) enzymes. T-EA showed a binding free energy towards the SIRT1 protein of ΔG_{bind (MM-GBSA)}: −30.98 ± 0.25 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −24.07 ± 0.30 kcal mol⁻¹, while that of CDK9 was ΔG_{bind (MM-GBSA)}: −29.50 ± 0.22 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −25.87 ± 0.40 kcal mol⁻¹. The obtained results from this research could be considered as important information on 3,4,3′-tri-O-methylellagic acid as a drug to treat cervical and breast cancers.

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3′-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment using in vitro and in silico approaches.     

Functionalization of Polycaprolactone Electrospun Osteoplastic Scaffolds with Fluorapatite and Hydroxyapatite Nanoparticles: Biocompatibility Comparison of Human Versus Mouse Mesenchymal Stem Cells

A capability for effective tissue reparation is a living requirement for all multicellular organisms. Bone exits as a precisely orchestrated balance of bioactivities of bone forming osteoblasts and bone resorbing osteoclasts. The main feature of osteoblasts is their capability to produce massive extracellular matrix enriched with calcium phosphate minerals. Hydroxyapatite and its composites represent the most common form of bone mineral providing mechanical strength and significant osteoinductive properties. Herein, hydroxyapatite and fluorapatite functionalized composite scaffolds based on electrospun polycaprolactone have been successfully fabricated. Physicochemical properties, biocompatibility and osteoinductivity of generated matrices have been validated. Both the hydroxyapatite and fluorapatite containing polycaprolactone composite scaffolds demonstrated good biocompatibility towards mesenchymal stem cells. Moreover, the presence of both hydroxyapatite and fluorapatite nanoparticles increased scaffolds’ wettability. Furthermore, incorporation of fluorapatite nanoparticles enhanced the ability of the composite scaffolds to interact and support the mesenchymal stem cells attachment to their surfaces as compared to hydroxyapatite enriched composite scaffolds. The study of osteoinductive properties showed the capacity of fluorapatite and hydroxyapatite containing composite scaffolds to potentiate the stimulation of early stages of mesenchymal stem cells’ osteoblast differentiation. Therefore, polycaprolactone based composite scaffolds functionalized with fluorapatite nanoparticles generates a promising platform for future bone tissue engineering applications.     

Langzeitergebnisse nach lumbalen Bandscheibenerkrankungen

The therapeutic results of operatively and conservatively treated patients with lumbar disc syndromes were reviewed in a retrospective study. The patients were treated during a 10-years period (1976-1985). A total of 330 patients with lumbar disc prolapses were treated in the hospital during this period 44% were treated surgically. The data on 100 operated and 100 conservatively treated cases, registered in this random test sample, have been compared with respect to: pain; neurological deficits; subjective problems and sociomedical questions. The average patient age of both groups was about 41 years, and the patients predominant were male (about 70%). The therapeutic results of both operatively and conservatively treated patients were good, which is also by the high percentage of employment (80%-90%) in the two treatment groups. The critical evaluation showed more neurological disturbances and limited vocational activity in the group of cases operated upon. More than 70% of the operated cases showed radicular syndromes of the follow-up examination although it was not of essential functional importance. The period inability to work and the percentage of disablement were also much higher in this group. The pain symptoms were particularly relevant in our examination. Only 12%-16% of the patients in the two groups that took part in the follow-up examinations reported freedom from pain. It was apparent that atypical pain syndromes were correlated with personality psychological disturbances. Nearly one-third of our patients mentioned psychological problems. The prognosis of the conservative treatment of lumbar disc prolapse was equivalent to operative therapy (disregarding the absolute indications for operations). There were no definite advantages found for either of the two methods of treatment. The necessity for a specialized follow-up treatment of patients with sciatica due to herniated lumbar discs is discussed, and differentiated selection for operative therapy is given. Here the treatment of pain should be considered most important.     

Recurrent Primary Cardiac Lymphoma on Aortic Valve Allograft: Implications for Therapy

Primary malignant cardiac lymphomas associated with grafts are extremely rare: to our knowledge, only 6 cases of prosthesis-associated B-cell lymphoma have been reported. Ours is the first report of recurrent diffuse large B-cell lymphoma associated with aortic valve allografts.We treated a 60-year-old man who presented in early 2007 with aortic valve endocarditis. He underwent aortic valve replacement with an allograft; the resected native valve showed active endocarditis without tumor. In January 2011, the patient underwent repeat aortic valve replacement because of symptomatic aortic regurgitation. The explanted valve specimen displayed diffuse large B-cell lymphoma. In September 2011, the patient presented with fever and a mass around the aortic valve. He died in January 2012. On autopsy, the explanted replacement valve displayed recurrent diffuse large B-cell lymphoma. The recurrent lymphoma on a new graft leads us to believe that this tumor is more aggressive than had been thought. We propose early systemic chemotherapy, in addition to tumor resection, for the possibility of a better prognosis. We discuss our patient''s case and review the relevant medical literature.     

Directing the Self‐Assembly of Mesostructured Hybrid Materials: Effect of Polymer Concentration and Solvent Type

Herein we explore the possibility to control the fabrication of non‐equilibrium nano‐patterns of spin‐coated organic‐inorganic hybrid materials based on diblock copolymers and metal nanoparticles in thin films. It is demonstrated that the type of solvent and the initial solution concentration, among other factors, can serve as tools to direct the morphology of spin‐coated thin films. The driving forces leading to the pattern formation are reviewed with respect to these parameters—type of solvents and polymer concentration. As a result well‐defined surface patterns of functional hybrid materials are obtained. Moreover, the same tools used to direct the pattern formation can be applied to gain control over the particle size and size distribution.