Beniamino Palmieri

Therapeutical use of probiotic formulations in clinical practice

Summary Background & Aims The spreading of gastrointestinal diseases is growing all over the world. Although for some of them an effective therapeutic approach has been found, palliation rather than cure is very frequent due to a partial knowledge of their aethiology and pathogenesis. This review, analyzing the main clinical studies, aims at being a state of the art update of the use of probiotic formulations in daily practice. Methods In this review we include all the most significant clinical trials involving the use of probiotic formulations for the treatment of several pathologies. Results Dysbiosis has been observed in irritable bowel syndrome patients. Probiotics may exert a beneficial effect on Crohn’s disease affected patients who have shown gut microbiota antigens and altered wall permeability. Moreover some probiotic formulations seem to enhance the therapy for Helycobacter Pylori reducing its pathogenic potential. Intestinal ecology imbalance has been also linked to cancer induction, allergy, skin and urogenital diseases. In addition probiotics administration seems to be particularly useful to ease post-operative complications. Conclusion Further future clinical trials, involving large numbers of patients, will be mandatory to achieve definite evidence of the preventive and curative role of probiotics in medical practice.

Clinical and experimental applications of sodium phenylbutyrate.

Histone acetyltransferase and histone deacetylase are enzymes responsible for histone acetylation and deacetylation, respectively, in which the histones are acetylated and deacetylated on lysine residues in the N-terminal tail and on the surface of the nucleosome core. These processes are considered the most important epigenetic mechanisms for remodeling the chromatin structure and controlling the gene expression. Histone acetylation is associated with gene activation. Sodium phenylbutyrate is a histone deacetylase inhibitor that has been approved for treatement of urea cycle disorders and is under investigation in cancer, hemoglobinopathies, motor neuron diseases, and cystic fibrosis clinical trials. Due to its characteristics, not only of histone deacetylase inhibitor, but also of ammonia sink and chemical chaperone, the interest towards this molecule is growing worldwide. This review aims to update the current literature, involving the use of sodium phenylbutyrate in experimental studies and clinical trials.

Multiple pathological events in exercised dystrophic mdx mice are targeted by pentoxifylline: outcome of a large array of in vivo and ex vivo tests

The phosphodiesterases inhibitor pentoxifylline gained attention for Duchenne muscular dystrophy therapy for its claimed anti-inflammatory, antioxidant, and antifibrotic action. A recent finding also showed that pentoxifylline counteracts the abnormal overactivity of a voltage-independent calcium channel in myofibers of dystrophic mdx mice. The possible link between workload, altered calcium homeostasis, and oxidative stress pushed toward a more detailed investigation. Thus a 4- to 8-wk treatment with pentoxifylline (50 mg x kg(-1) x day(-1) ip) was performed in mdx mice, undergoing or not a chronic exercise on treadmill. In vivo, the treatment partially increased forelimb strength and enhanced resistance to treadmill running in exercised animals. Ex vivo, pentoxifylline restored the mechanical threshold, an electrophysiological index of calcium homeostasis, and reduced resting cytosolic calcium in extensor digitorum longus muscle fibers. Mn quenching and patch-clamp technique confirmed that this effect was paralleled by a drug-induced reduction of membrane permeability to calcium. The treatment also significantly enhanced isometric tetanic tension in mdx diaphragm. The plasma levels of creatine kinase and reactive oxygen species were both significantly reduced in treated-exercised animals. Dihydroethidium staining, used as an indicator of reactive oxygen species production, showed that pentoxifylline significantly reduced the exercise-induced increase in fluorescence in the mdx tibialis anterior muscle. A significant decrease in connective tissue area and profibrotic cytokine transforming growth factor-beta(1) was solely found in tibialis anterior muscle. In both diaphragm and gastrocnemius muscle, a significant increase in neural cell adhesion molecule-positive area was instead observed. This data supports the interest toward pentoxifylline and allows insight in the level of cross talk between pathogenetic events in workloaded dystrophic muscle.

Intra-Articular Injections for the Treatment of Osteoarthritis Focus on the Clinical Use of Hyaluronic Acid

Osteoarthritis (OA), also called degenerative joint disease, is the most frequently occurring chronic musculoskeletal disease, particularly affecting the aging population. The use of viscosupplementation, i.e. intra-articular (IA) hyaluronic acid (HA) drug therapy, to treat OA, is growing worldwide, due to important results obtained from several clinical trials, which reported IA HA-related improvements in functional activity and pain management. This review is an update of the IA use of this compound in the treatment of OA, with clinical evidence from the last few years being discussed and used to delineate new trends for the future.

Mechanisms and therapeutic effectiveness of lactobacilli

The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword ‘Lactobacillus’. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects.

Delayed nipple-sparing modified subcutaneous mastectomy: Rationale and technique

Abstract:  The problem of nipple‐areola complex (NAC) preservation during mastectomy is a very intriguing and stimulating issue. In fact, in order to perform an oncologically safe operation, no mammary tissue (enclosed in the main galactophoric ducts) should remain; on the other hand, without the blood supply coming from the breast gland, NAC viability is greatly impaired because the surrounding vascular dermal network is not developed enough to support its metabolic requirements. We suggest therefore a two‐step surgical procedure. The first step, on an outpatient basis with local tumescent anesthesia, is a mini‐invasive cutting and coagulating procedure. It addresses the autonomization of the vascular supply to the NAC by detaching the galactophore stalk from the nipple and coagulating the deep vascular plexus. The second step, under general anesthesia and again with tumescent technique, removes the breast within its capsule, with careful checks of any remnant and adequate approach to the axilla. A subpectoralis prosthesis completes the procedure. In our view, this technique is electively suitable for prophylactic mastectomy, but also for stage I breast cancer, 2.5 cm from the NAC and 1.5 cm from the skin and pectoralis fascia, and it is very safe, simple, and effective.

Past, present and future of myoblast transplantation in the treatment of Duchenne muscular dystrophy

Palmieri B, Tremblay JP, Lodi D. Past, present and future of myoblast transplantation in the treatment of Duchenne muscular dystrophy.
Pediatr Transplantation 2010: 14:813–819.

An Update on the Therapeutic Role of Alkylglycerols

Scandinavian folk medicine used shark liver oil for the treatment of cancers and other ailments based on the rarity of tumors in sharks and their ability to resist infections. Shark liver oil is a source of alkylglycerols which have been studied as anti-cancer agents in several clinical trials. Moreover, alkylglycerols have been investigated for the treatment of radiation induced side effects and for their ability to boost the immune system. Several experimental studies have shown the ability of alkylglycerols to open the blood brain barrier to facilitate the access of therapeutic drugs to the central nervous system. This review covers the most important studies of alkylglycerols in both animals and humans.

Influence of hyaluronic acid on bacterial and fungal species, including clinically relevant opportunistic pathogens.

Hyaluronic acid (HA) has several clinical applications (aesthetic surgery, dermatology, orthopaedics and ophtalmology). Following recent evidence, suggesting antimicrobial and antiviral properties for HA, we investigated its effects on 15 ATCC strains, representative of clinically relevant bacterial and fungal species. The in vitro system employed allowed to assess optical density of broth cultures as a measure of microbial load in a time-dependent manner. The results showed that different microbial species and, sometimes, different strains belonging to the same species, are differently affected by HA. In particular, staphylococci, enterococci, Streptococcus mutans, two Escherichia coli strains, Pseudomonas aeruginosa, Candida glabrata and C. parapsilosis displayed a HA dose-dependent growth inhibition; no HA effects were detected in E. coli ATCC 13768 and C. albicans; S. sanguinis was favoured by the highest HA dose. Therefore, the influence of HA on bacteria and fungi warrants further studies aimed at better establishing its relevance in clinical applications.

Inflammation and Genetics: An Insight in the Centenarian Model

Abstract The number of centenarians is growing worldwide. This specific cohort has aroused the attention of scientists worldwide and is considered one of the most valuable models to study the mechanisms involved in the aging process. In fact, they have reached the extreme limits of human life span and, most important of all, they show relatively good health being able to perform their routine daily life. Because they have escaped the common lethal diseases, the role of their genetic background has been brought into focus. In fact, sequence variations, in a variety of pro- or anti-inflammatory cytokine genes, have been found to influence successful ageing and longevity. The key role played by cytokines has been also confirmed in centenarians as we know that inflammation has been related to several pathological burdens (e.g., obesity, atherosclerosis, and diabetes). Successful ageing seems to be related to an optimal functioning of the immune system, pointing out that polymorphisms for the immune system genes, which are involved in the regulation of immune-inflammatory responses, may play a key role in the genetics of ageing. This review provides an update in the field of ageing related to inflammation and genetics.