The aim of this study was to encapsulate, thymol, in natural polymers in order to obtain (i) taste masking effect and, then, enhancing its palatability and (ii) two formulations for systemic and ...local delivery of herbal drug as adjuvants or substitutes to current medications to prevent and treat several human and animal diseases. Microspheres based on methylcellulose or hydroxypropyl methylcellulose phthalate (HPMCP) were prepared by spray drying technique. Microparticles were in vitro characterized in terms of yield of production, drug content and encapsulation efficiency, particle size, morphology and drug release. Both formulations were in vivo orally administered and pharmacokinetic analysis was carried out. The polymers used affect the release and, then, the pharmacokinetic profile of thymol. Encapsulation into methylcellulose microspheres leads to short half/life but bioavailability remarkably increases compared to the free thymol. In contrast, enteric formulation based on HPMCP shows very limited systemic absorption. These formulations could be proposed as alternative or adjuvants for controlling pathogen infections in human or animal. In particular, methylcellulose microspheres can be used for thymol systemic administration at low doses and HPMCP particles for local treatment of intestinal infections.
Niemann–Pick disease is an inherited lipid storage disorder caused by the deficiency of acid sphingomyelinase, which results in accumulation of sphingomyelin within cells of several organs and ...consequent tissue damage. The broad clinical spectrum of this disorder may overlap with that of systemic lupus erythematosus, hindering differential diagnosis. Herein, we report the case of a patient affected by Niemann–Pick type B disease intertwined with clinical and serological features of systemic lupus erythematosus. Two novel mutations in the SMPD1 gene were found in compound heterozygosity: p.A36V and IVS2 + 8 T > G.
We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any ...one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2-34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of-life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure.
In HIV-infected patients with HCV-related chronic hepatitis, liver impairment and drug toxicity may substantially reduce the number of possible therapeutic options.
we here describe the case of an ...HCV-HIV coinfected woman who had repeated severe episodes of drug-related liver toxicity with indinavir, saquinavir, fosamprenavir, and darunavir, with minimal further therapeutic options left in this class. Previous treatment-limiting side effects with efavirenz and nevirapine also precluded use of non-nucleoside reverse transcriptase inhibitors. Introduction of an integrase-inhibitor regimen based on raltegravir, tenofovir, and emtricitabine allowed a prompt achievement of undetectable viral load and a substantial rise of CD4 count to high levels, with no subsequent episodes of hepatic toxicity, and no other side effects.
given the relatively common prevalence of HCV-related chronic hepatitis among people with HIV, raltegravir might represent an important alternative option for a substantial number of patients who cannot be treated with protease inhibitors or NNRTI because of drug-related hepatic toxicity.
Background
Icatibant is a bradykinin B2‐receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1‐inhibitor deficiency. Treatment is not adjusted by body weight ...however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real‐world safety and effectiveness of icatibant.
Methods
Attack and treatment characteristics as well as outcomes following treatment with icatibant were compared among patients with underweight, normal, overweight, and obese BMI.
Results
Data from 2697 icatibant‐treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of underweight, normal, overweight, and obese BMI, respectively) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks and more abdominal attacks. Most attacks (71.9–83.8%) were treated with a single icatibant injection without the need for rescue with plasma‐derived C1‐inhibitor (pdC1‐INH), regardless of BMI. Patients with obese BMI used pdC1‐INH as rescue treatment more often (P < 0.0001; P = 0.0232 excluding 2 outliers) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P < 0.001 for overweight and P < 0.05 for obese versus normal).
Conclusion
Overall, icatibant was comparatively effective in treating attacks in patients across all BMI groups.
Trial registration NCT01034969.
Icatibant, an antagonist of the bradykinin B2 receptor, was approved for the treatment of acute attacks of hereditary angioedema in the EU in 2008. This paper presents the case of a 65-year-old woman ...affected by frequent acute attacks of hereditary angioedema who benefitted from a change of therapy to icatibant, following years of treatment with C1-inhibitor.
Autoimmune complications in the context of primary immunodeficiency diseases represent a well-known phenomenon, and this is widely recognized also for Selective Immunoglobulin A deficiency (IgAD), ...the most common primary antibody deficiency (PAD). Relapsing polychondritis (RP) is a rare immune-mediated, difficult to treat, disorder in which the cartilaginous tissues are the target for inflammation and damage. Ocular inflammatory manifestations in RP are frequent and often sight-threatening. Antiphospholipid syndrome (APS) is an acquired prothrombotic state related to circulating autoantibodies against phospholipids and/or their cofactors. Rare reports of APS associated to RP, PAD and APS or PAD and RP are available.
Silicone-gel breast implants (SBI) have been widely used for breast augmentation. Although silicone is generally considered an inert substance, there has been much debate recently on its role in ...inducing chronic inflammation and systemic connective tissue diseases. The case of a young woman affected by Raynaud's Phenomenon (RP), worsening of vitiligo and of autoimmune thyroiditis following SBI is reported in this paper. Removal of SBI led to temporary RP remission; however, despite notable clinical improvement, nailfold capillary microscopy showed progressive microcirculatory abnormalities consistent with a diagnosis of early scleroderma. Follow-up of the patient led to the diagnosis of Systemic Sclerosis (SSc) with pulmonary hypertension. The development of SSc after SBI is described, a condition that falls into the recently recognized “ASIA” (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome. Nailfold capillary microscopy is a valuable tool in early SSc diagnosis, in monitoring disease activity and in establishing the risk of an aggressive course of connective tissue disease following silicone breast implantation. The relationship between silicone and the immune system requires further reports and investigation in order to determine the main individual risk factors predisposing to the wide spectrum of adjuvant-induced responses.
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