Anti-inflammatory Effects of Novel P2X4 Receptor Antagonists,NC-2600 and NP-1815-PX,in a Murine Model of Colitis

Inflammation - The pharmacological blockade of P2X4 receptors has shown potential benefits in the management of several immune/inflammatory diseases. However, data regarding the involvement of P2X4...     

The genetics of signal transduction and the outcome of diagnostic tests in growth retardation.

The effects of 'normal' genetic variability of signal transduction on endocrine function may be more evident during stimulation tests than is observed in basal states, thereby contributing to a greater understanding of the possible role of signal transduction genetics in the pathogenesis of endocrine disorders. In the present study, we have studied the outcome of growth hormone (GH) stimulation testing by insulin in growth-retarded children in relation to the genotype of ACP1 (acid phosphatase locus 1; also referred to as cLMWPTP, cytosolic low molecular weight phosphotyrosine phosphatase). ACP1 is an enzyme, expressed as two distinct isoforms designated F and S, that down-regulates insulin receptor signal transduction and which shows a genetic polymorphism with strong quantitative enzymatic differences among genotypes. In this study, we examined 116 growth-retarded children of which 101 were genotyped for ACP1. We found that the basal level of GH is higher in ACP1 genotypes with low concentrations of the S isoform than in genotypes with high S isoform concentrations (P<0.02). Additionally, during GH stimulation with insulin, the genotypes with low S isoform concentrations were found to perform better (P<0.005) and to react more promptly than the genotypes with high S isoform concentrations (P<0.05). These findings suggest that high S isoform ACP1 activity slows down the effect of insulin, resulting in a retardation of its metabolic effect.     

Gender-specific association of <Emphasis Type="Italic">ADA</Emphasis> genetic polymorphism with human longevity

Aim of this study was to investigate whether the polymorphic ADA (Adenosine Deaminase, EC 3.5.4.4) gene, which determines the cellular level of adenosine and plays a crucial role in the regulation of the immune system and in the control of metabolic rates, is involved in longevity. 884 unrelated healthy individuals (age range 10–106 years, 400 males and 484 females) from central Italy were studied. ADA genotyping was performed by RFLP-PCR. Frequency distributions were compared using the chi-square test and a three-way contingency table analysis by a log linear model was applied to test independence between the variables. We found that ADA influences human life-span in a sex and age specific way. An increased frequency of ADA*2 carriers was found in males aged 80–85, and a decreased frequency in males over 85 (χ² = 13.93; df = 3; P = 0.003); significant differences among the age groups was not found in females. A strong interaction among age groups, ADA genotype and sex (G = 15.086; df = 3; P = 0.0017) was found. Males aged 80–85 could be protected from ischemic stroke by higher levels of adenosine (determined by the ADA*2 allele). The decrease of ADA*2 carriers in males over 85 may depend essentially on immunological factors; reduced levels of adenosine protect from asthma and other pulmonary diseases and lead to a reduced activation of inflammatory cells and pro-inflammatory cytokines production. Moreover, the low level of adenosine may potentiate the activity of NK and other cellular effectors against tumor cells. The negligible effect of ADA genetic polymorphism in females suggest a marginal influence of genetic factors in determining longevity in this sex, confirming previous reports.     

Spontaneous clostridial myonecrosis after pregnancy – emergency treatment to the limb salvage and functional recovery: a case report

Clostridial myonecrosis (CM) is a rare, life threatening necrotizing infection of a skeletal muscle caused by Clostridium perfringens in the majority of cases. The diagnosis may be difficult because of few diagnostic and cutaneous signs early in its course. Standard therapy involves surgical debridements of a devitalized tissue and high‐dose organism‐specific antibiotic therapy. The hyperbaric oxygen has also showed its usefulness in the treatment of these infections. Autograft systems as tissue replacement, based on bioengineered materials, have been demonstrated to be safe and effective treatments for chronic wounds and a suitable physiotherapy is recommended for the recovery of functional impairments of upper extremities. We present a rare case of CM of right upper limb treated with a combination of standard treatments and new techniques.     

Combined use of super‐oxidised solution with negative pressure for the treatment of pressure ulcers: case report

A 61‐year‐old patient was affected by flaccid paraplegia for 20 years because of post‐traumatic medullar injury caused by an accidental fall, with stage IV sacral pressure ulcer for 3 years. The patient later developed stage IV sacral pressure ulcer. After 6 months, a new granulation tissue formation appeared in the wound and a reduction of its diameter was observed (length 20 cm, width 15 cm, depth 5 cm). We therefore treated the wound with PRP (platelet rich plasma) intra‐lesion and peri‐lesional injections. The wounds were covered with three‐dimensional polymerised hyaluronic acid medicated biologic dressing. After the surgery, a moderate reduction in diameter and the depth was observed. Super‐oxidised solution (SOS‐Dermacyn) was applied to control infection locally together with negative pressure to control the exudate and the local bacteremia, to avoid infectious complications without application of systematic antibiotic therapy.