Alloantigen-induced human lymphocytes rendered nonresponsive by a combination of anti-CD80 monoclonal antibodies and Cyclosporin-A suppress mixed lymphocyte reaction in vitro

Induction of a state of long-term, alloantigen-specific T cell nonresponsiveness has significant implications for human transplantation. It has been previously described that alloantigen-specific anergy may be induced by addition of cyclosporin-A together with anti-CD80(B7-1) mAb to a MLR. In this study we endeavored to verify whether alloantigen-induced PBL rendered anergic by the addition of a combination of anti-B7 mAb and cyclosporin-A during a MLR had a suppressive effect when added to autologous lymphocytes activated in MLR. We found that: 1) the addition of cells rendered anergic by this procedure to a MLR suppress both proliferative and cytotoxic response of autologous responsive PBL to either the same or third-party stimulator cells; 2) the suppressive effect is limited to alloantigen-induced T cell activation, as addition of anergic cells does not influence mitogen- or antigen-induced proliferation of autologous responsive T cells; 3) nonresponsiveness of suppressed cells cannot be reversed by either subsequent restimulation with allogeneic cells or addition of exogenous IL-2 to the cultures; 4) the suppressive effect is apparently not due to secretion of anergic cell-derived soluble factors, but it seems to be dependent on cell-cell contact between anergic, responsive, and stimulator cells. These data suggest that: 1) the delivery of a direct signal mediated by anergic lymphocytes through a cell-cell contact is likely to be the mechanism responsible for the suppressive effect here described; 2) anergic cells may propagate alloantigen-specific tolerance to potentially responsive autologous lymphocytes. Preliminary experiments indicate that anti-CD86(B7-2) mAb may play a similar role in the generation of alloantigen-induced nonresponsiveness

Natural cytotoxicity impairment in familial haemophagocytic lymphohistiocytosis.

Ten children with the characteristic clinical and haematological features of haemophagocytic lymphohistiocytosis are reported. Four patients treated with a combination of drugs comprising etoposide, methotrexate, and steroids were in complete remission after 10 to 30 months. Natural cytotoxic mechanisms including natural killer cell activity, antibody dependent cell mediated cytotoxicity, lymphokine activated killer cell activity, and natural killer cell like activity were persistently absent or severely impaired in these four patients despite their clinical remission. Their parents and one healthy sibling also had impaired natural cytotoxic mechanisms. Constitutional impairment of natural cytotoxic mechanisms could be important in the pathogenesis of haemophagocytic lymphohistiocytosis

Suspected severe malaria in a sudanese patient affected by sickle cell disease who was treated with hydroxyurea

Sickle cell disease (SCD) is the most common genetic disease in sub-Saharan Africa. The signs and symptoms of SCD usually begin in early childhood. Characteristic features of this disorder include anaemia, repeated infections, and periodic episodes of pain. Malaria is one of the infections that can occur in patients with SCD in endemic countries. Many guidelines recommend antimalarial chemoprophylaxis in these patients, although the debate on which drug should be used is still ongoing. Hydroxyurea (HU), which is considered a safe and effective treatment for both children and adults with SCD, seems to affect the incidence and severity of malaria, although these impacts have yet to be fully demonstrated. We report a case of an eight-and-a-half-year-old Sudanese boy with SCD treated with HU admitted for suspected severe malaria who showed a recrudescence after first-line treatment. Although he had undergone splenectomy and thus belonged to a category of patients at high risk for infectious complications, he was not receiving any malaria chemoprophylaxis. This case emphasises the importance of the routine administration of malaria prophylaxis to children with SCD living in endemic areas, even when they are treated with HU, and especially if they are at high risk for infectious complications because they have undergone splenectomy. There is an urgent need for further research to evaluate the most appropriate regimen and its optimal duration

Antimicrobial efficacy assessment and rheological investigation of two different hand sanitizers compared with the standard reference WHO formulation 1

(1) Background: recently, the use of alcohol-based hand sanitizers (ABHSs) has become very frequent, and an evaluation of the stability and effectiveness of their formulations is a critical topic which should be carefully considered. (2) Methods: starting from the characterization of the hand sanitizers object of the study, our interest was focused on their rheological behavior in order to confirm their intrinsic features, but also the stability of each formulation in different conditions of shear and temperature; the second aspect concerns the antimicrobial assessment through a panel of in vitro and in vivo experimental trials. (3) Results: rheological investigation confirmed good stability for the two hand sanitizers in gel formula with respect to the reference in liquid formula; the antimicrobial activity evaluation showed good efficacy of each formulation both in vitro and in vivo. (4) Conclusions: altogether, our overview presents a valid quality control assessment to ensure the stability and efficacy of an alcohol-based hand sanitizer

Comparative physicochemical analysis among 1,4-butanediol diglycidyl ether cross-linked hyaluronic acid dermal fillers

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used in several chirurgical practices and in aesthetic medicine. HA filler stability can be enhanced through different cross-linking technologies; one of the most frequently cross-linker used is 1,4-butanediol diglycidyl ether (BDDE), also present in the HA-BDDE dermal filler family of the company Matex Lab S.p.A. (Brindisi, Italy). Our overview is focused on their characterization, drawing a correlation between matrix structure, rheological and physicochemical properties related to their cross-linking technologies. (2) Methods: Four different injectable HA hydrogels were characterized through optical microscopic examination and rheological behavior investigation. (3) Results: The cross-linked HA dermal fillers showed a fibrous \u201cspiderweb-like\u201d matrix structure and an elastic and solid-like profile. (4) Conclusions: The comparative analysis represents a preliminary characterization of these injectable medical devices in order to identify their best field of application

A practical approach for the in vitro safety and efficacy assessment of an anti-ageing cosmetic cream enriched with functional compounds

(1) Background: Cosmeceuticals are topical products applied to human skin to prevent skin ageing and maintain a healthy skin appearance. Their effectiveness is closely linked to the compounds present in a final formulation. In this article, we propose a panel of in vitro tests to support the efficacy assessment of an anti-ageing cream enriched with functional compounds. (2) Methods: biocompatibility and the irritant effect were evaluated on reconstructed human epidermis (RHE) and corneal epithelium (HCE) 3D models. After a preliminary MTT assay, normal human dermal fibroblasts (NHDF) and keratinocytes (HaCaT) were used to evaluate the extracellular matrix (ECM) protein synthesis, and interleukin-6 (IL-6) and metalloproteinase-1 (MMP-1) production. (3) Results: data collected showed good biocompatibility and demonstrated the absence of the irritant effect in both 3D models. Therefore, we demonstrated a statistical increase in collagen and elastin productions in NHDF cells. In HaCaT cells, we highlighted an anti-inflammatory effect through a reduction in IL-6 levels in inflammatory stimulated conditions. Moreover, the reduction of MMP-1 production after UV-B radiation was demonstrated, showing significant photo-protection. (4) Conclusion: a multiple in vitro assays approach is proposed for the valid and practical assessment of the anti-ageing protection, anti-inflammatory and biocompatible claims that can be assigned to a cosmetic product containing functional compounds

The anti-ageing and whitening potential of a cosmetic serum containing 3-o-ethyl-l-ascorbic acid

Skin ageing has many manifestations such as wrinkles, dryness, hyperpigmentation, and uneven skin tone. Extrinsic and intrinsic factors, especially solar ultraviolet light (UVB), contribute to skin ageing; its main features are brown spots, alterations in melanin pigmentation, and a decrease in collagen and hyaluronic acid linked to oxidative stress. Several studies showed that topical products containing ingredients with antioxidant activity can reduce oxidative damage; to provide a maximum anti-ageing effect to the skin, topical products can combine various ingredients. C-SHOT SERUM contains a combination of two molecules with a proven anti-ageing activity: a high percentage (30%) of a more stable vitamin C derivative, 3-O-ethyl-L-ascorbic acid, and lactic acid (1%). The product showed a high biocompatibility, assessed through an MTT assay on keratinocytes and on Reconstructed Human Epidermis (RHE, SkinEthic); the anti-ageing activity was demonstrated on human dermal fibroblasts and keratinocytes by a statistically significant increase in collagen production and a reduction of a UVB-induced DNA damage marker (\u3b3-H2AX histone), indicating DNA protection. Moreover, a depigmenting activity, shown by a highly significant decrease in melanin content on treated Reconstructed Human Pigmented Epidermis (RHPE), was assessed. According to the data of our study, the tested product contrasts the effect of skin ageing and irregular pigmentation due to the physiological decline of the skin