Nanoarchitectures for efficient IgE cross-linking on effector cells to study amoxicillin allergy

Background

Amoxicillin (AX) is nowadays the β-lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo tests and non-optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic. Knowing adduct structural features for promoting effector cell activation would help to improve in vitro tests. We aimed to identify the optimal structural requirement in specific cellular degranulation to AX using well-precised nanoarchitectures of different lengths.

Method

We constructed eight Bidendron Antigens (BiAns) based on polyethylene glycol (PEG) linkers of different lengths (600–12,000 Da), end-coupled with polyamidoamine dendrons that were terminally multi-functionalized with amoxicilloyl (AXO). In vitro IgE recognition was studied by competitive radioallergosorbent test (RAST) and antibody–nanoarchitecture complexes by transmission electron microscopy (TEM). Their allergenic activity was evaluated using bone marrow-derived mast cells (MCs) passively sensitized with mouse monoclonal IgE against AX and humanized RBL-2H3 cells sensitized with polyclonal antibodies from sera of AX-allergic patients.

Results

All BiAns were recognized by AX-sIgE. Dose-dependent activation responses were observed in both cellular assays, only with longer structures, containing spacers in the range of PEG 6000–12,000 Da. Consistently, greater proportion of immunocomplexes and number of antibodies per complex for longer BiAns were visualized by TEM.

Conclusions

BiAns are valuable platforms to study the mechanism of effector cell activation. These nanomolecular tools have demonstrated the importance of the adduct size to promote effector cell activation in AX allergy, which will impact for improving in vitro diagnostics.

     

Royal- jelly- based apitherapy can attenuate damages to male reproductive parameter following nicotine administration

Background : Nicotine administration can generate severe oxidative stress and lipid peroxidation. Royal jelly, with its antioxidant properties, acts as a scaven...     

Clinical aspects of miliary tuberculosis in Saudi adults.

OBJECTIVE: To review all cases of miliary tuberculosis (MT) over a period of 7 years in a Saudi Arabian population, to determine the clinical and laboratory characteristics and diagnostic methods, and to compare our data with others reported in the literature. DESIGN: A retrospective case review. RESULTS: Of 780 cases of active tuberculosis seen over period of 7 years, 47 (6%) had MT. The majority of the patients were aged over 60 years (68%). The most common symptoms were fever and weight loss. Risk factors were present in 70% of cases, mainly diabetes mellitus, history of prior tuberculosis, chronic liver and renal disease, immunosuppressive drug therapy and malignancy. Miliary pattern on chest radiography was seen in 89%. The most common laboratory abnormalities were anemia (66%), lymphopenia (89%), low albumin (87%), and high alkaline phosphatase (80%). Fiberoptic bronchoscopy was diagnostic in 7/10 (70%), bone marrow examination in 8/11 (73%), and liver biopsy in 14/16 (88%). High alkaline phosphatase and lymphopenia were associated with high yield of liver biopsies and bone marrow examination: 13/14 (93%) and 7/8 (88%), respectively. Death occurred in 10/47 (21%); all of these had radiological evidence of miliary pattern, and 80% had comorbid conditions. CONCLUSION: These data confirm and extend the results of other studies and suggest that MT is a disease of the elderly and immunocompromised, and is associated with high mortality. A high index of suspicion is required for diagnosis.     

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus

Background: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease.

Objective: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.

Methods: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.

Results: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.

Conclusions: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.     

Pulmonary radiological findings in hepatoma

Pulmonary radiological features of 27 patients with a diagnosis of hepatoma were reviewed and compared with 64 controls. Coin shadows, nodular, lymphangitic or hilar node metastases were observed in 50% of the hepatoma cases. Other radiological pulmonary findings in hepatoma included statistically significant elevation of the right hemidiaphragm, double contour of the diaphragmatic silhouette and discoid atelectasis. Left hemidiaphragm changes may occur with left lobe involvement. Double contour of the crest of the diaphragm appeared to be specific and common in hepatoma in this African population. Doming of the diaphragm was not specific to hepatoma.     

Antioxidant Activity of Iranian Echium amoenum Fisch & C.A. Mey Flower Decoction in Humans: A cross-sectional Before/After Clinical Trial

Medicinal plants are recognized as sources of natural antioxidants that can protect from biological system oxidative stress. The present cross-sectional before/after clinical trial was carried out to investigate the antioxidant properties of the decoction of the flowers of Echium amoenum Fisch & C.A. Mey in humans. A group of 38 healthy subjects was invited to use the E. amoenum (7 mg kg(-1)) twice daily for 14 days. Blood samples before and after entering the study were measured for lipid peroxidation level (LPO), total antioxidant capacity (TAC) and total thiol (SH) molecules. A significant reduction of blood LPO (24.65 +/- 11.3 versus 19.05 +/- 9.7, P = 0.029) was observed after 14 days of E. amoenum consumption. Blood TAC (1.46 +/- 0.51 versus 1.70 +/- 0.36, P = 0.018) and total thiol molecules (0.49 +/- 0.11 versus 0.56 +/- 0.12, P = 0.001) increased after 14 days of E. amoenum consumption. In conclusion, this antioxidative stress potential of E. amoenum may be due to its bioactive antioxidant components, especially rosmarinic acid and flavonoids. In recent years the importance of oxidative stress in the pathophysiology of many human disorders has been confirmed, thus use of this plant as a dietary supplement is highly recommended.