The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres.

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for alpha-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a beta-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.     

Seroepidemiological study on human brucellosis in Assiut Governorate

Brucellosis is the most important zoonotic disease constituting a public health problem in Assiut Governorate, hence this study was carried out to determine the prevalence of brucellosis among humans in Assiut Governorate. A total of 7154 peripheral blood samples were collected from patients with fever at Assiut Fever Hospital during the period from 2002-2003. A full detailed anamnestic and clinical assessment in the form of questionnaire was designed for each individual to determine the risk factors with specific emphasis to age, sex, residence and occupation. All serum samples were screened for Brucella antibodies by slide agglutination test. Positive sera were further analyzed by standared tube agglutination test. Enzyme linked immunosorbent assay (ELISA) was carried out to detect IgM and IgG Brucella antibodies. Statistical analysis was performed and correlation coefficient was done between all risk factors. Results declared that the prevalence of brucellosis was (1.29 +/- 0.004 %) and (1.22 +/- 0.002 %) as detected by agglutination and ELISA, respectively. IgM antibodies were estimated in 9.8 % of the examined patients, while IgG antibodies were found in 30.4 % of the examined patients, moreover both IgM and IgG antibodies were detected in 54.3 % of the examined patients. The prevalence of brucellosis was significantly (P < 0.05) affected by sex, where the rate of detection was higher among females (1.76 +/- 0.009 %) than males (1.05 +/- 0.004 %) as detected by agglutination test. On the other hand, the prevalence rate based on ELISA was (1.64 +/- 0.39 % and 1.01 +/- 0.89 %) for females and males, respectively. Prevalence of brucellosis was higher in rural areas (1.3 +/- 0.005 % & 1.25 +/- 0.009 %) than in urban areas (1.23 +/- 0.001% & 1.12 +/- 0.01 %) as detected by agglutination test and ELISA, respectively. The prevalence of brucellosis varied significanctly between different occupational and age groups. Public health impact of brucellosis is discussed and suggestive measures for control are explained.     

Involvement of ICAM-1 in bone metabolism: a potential target in the treatment of bone diseases?

Bone diseases such as osteoporosis, osteoarthritis and rheumatoid arthritis (RA) affect a great proportion of individuals, with debilitating consequences in terms of pain and progressive limitation of function. Existing treatment of these pathologies has been unable to alter the natural evolution of the disease and, as such, a clearer understanding of the pathophysiology is necessary in order to generate new treatment alternatives. One therapeutic strategy could involve the targeting of intercellular adhesion molecule-1 (ICAM-1; CD54). In bone, ICAM-1 is expressed at the surface of osteoblasts (Obs) and its counter-receptor, leukocyte function-associated antigen-1 (LFA-1; CD11a), at the surface of osteoclast (Oc) precursors. ICAM-1 blockade between the Ob and the pre-Oc results in an inhibition of Oc recruitment and a modulation of inflammation, which could potentially help in controlling disease activity in bone pathologies. So far, clinical studies on ICAM-1 blockade in bone diseases have been limited to RA. A better understanding of the implication of this adhesion molecule in Ob/Oc interactions and inflammatory mediation in the bone pathological state, however, is needed. As new discoveries on the role of this adhesion molecule are being reported, ICAM-1 could become a potential target for other bone diseases as well.     

Transit time ultrasound perivascular flow probe technology is superior to MR imaging on hepatic blood flow measurement in a porcine model

Background: The hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound(TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI(PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events. Methods: Eighteen large white pigs were anaesthetized for PC-MRI and approximately 75% hepatic resection was performed under a unified protocol. The blood flow was measured in the hepatic artery(Qha), the portal vein(Qpv), and the aorta above the celiac trunk(Qca) using PC-MRI, and was compared to the TTUS probe. The Bland-Altman method was conducted and a partial least squares regression(PLS) model was implemented. Results: The mean Qpv measured in PC-MRI was 0.55 ± 0.12 L/min, and in the TTUS probe was 0.74 ± 0.17 L/min. Qca was 1.40 ± 0.47 L/min in the PC-MRI and 2.00 ± 0.60 L/min in the TTUS probe. Qha was 0.17 ± 0.10 L/min in the PC-MRI, and 0.13 ± 0.06 L/min in the TTUS probe. The Bland-Altman method revealed that the estimated bias of Qca in the PC-MRI was 32%(95% CI:-49% to 15%); Qha 17%(95% CI:-15% to 51%); and Qpv 40%(95% CI:-62% to 18%). The TTUS probe had a higher weight in predicting adverse outcomes after 75% resection compared to the PC-MRI( β= 0.35 and 0.43 vs β = 0.22 and 0.07, for tissue changes and premature death, respectively). Conclusions: There is a tendency of the PC-MRI to underestimate the flow measured by the TTUS probes. The TTUS probe measures are more predictive of relevant post-hepatectomy outcomes.     

Left atrial deformation analysis as a predictor of severity of coronary artery disease

Background

Two-dimensional (2D) speckle-tracking strain imaging is a novel method for assessment of regional myocardial deformation that uses tracking of acoustic speckles or kernels rather than Doppler myocardial velocities. It has been suggested that Left atrial (LA) strain as measured by 2D speckle tracking can be used to evaluate dynamic LA function.

Intravascular evaluation of coronary atherosclerotic lesions among Egyptian diabetic patients with acute coronary syndromes

Background

Coronary artery disease is one of the main causes of death in diabetes mellitus (DM). Egypt was listed among the world top 10 countries regarding the number of diabetic patients by the International Diabetes Federation (IDF).

Does No-Touch Technique Better than Conventional or Intermediate Saphenous Vein Harvest Techniques for Coronary Artery Bypass Graft Surgery: a Systematic Review and Meta-analysis

Saphenous vein (SV) is a common graft being used in coronary artery bypass grafting (CABG). Conventional (CON), intermediate (I), and no-touch (NT) are the most common harvesting techniques of SV for CABG. The aim of this study is to systematically review the NT versus CON and I techniques in harvesting SV for CABG. Twelve databases were searched for randomized controlled trials comparing the CON, I, and NT techniques in harvesting SV for CABG. Twelve reports of six RCTs were included. Our meta-analysis showed that with NT technique, patency rate was significantly higher when compared to I technique up to 18-month follow-up duration. In contrast, this significant difference was not maintained in terms of minor complications of leg wounds with both techniques. The NT has significantly higher patency rate compared to I vein harvesting technique. However, more RCTs are warranted to confirm these results.     

Value of Soluble Transferrin Receptors and sTfR/log Ferritin in the Diagnosis of Iron Deficiency Accompanied by Acute Infection

There are many causes of anemia; the most common of these are acute and chronic infections, iron deficiency, or both. Identifying the cause is a very important step in management of anemia. So, we evaluated the usefulness of soluble transferrin receptor (sTfR) and of the sTfR/log ferritin in the diagnosis of iron deficiency anemia accompanied by acute infection. This study was conducted on 131 children aged 2–11 years old from those who attended the pediatric outpatient clinics in Menoufia university hospital. Hematological indices, iron balance and sTfR were evaluated and the sTfR/log F was calculated for each examined child. From the examined children four groups were distinguished: Group I (control): included 34 healthy children with normal iron status (66.7% males, age 4.2 ± 1.2). Group II (IDA): included 38 children diagnosed as iron deficiency anemia (47.4% males, age 4.9 ± 1.6). Group III (IDA + infection): included 26 children with infectious disease (upper respiratory tract infection, otitis media, pneumonia, stomatitis, and urinary tract infection) and anemia meeting criteria of IDA (50% males, age 4.2 ± 0.7). Group IV (anemia + infection): included 33 children with infectious anemia without iron deficiency (56.2% males, age 5.06 ± 1.4). It was proved that sTfR and sTfR/log Ferritin were significantly higher in children with anemia due to iron deficiency, and in those with infection + iron deficiency, versus those with infectious anemia or in healthy children. The use of sTfR and sTfR/log ferritin improves the diagnosis of IDA in pediatric patients, especially in the presence of coexisting acute infection.     

Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC?+?CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p?<?0.0001, OR?=?4.9, 95% CI?=?2.7–8.8; p ? 0.0001, OR?=?3.6, 95% CI?=?2.2–5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC?+?CC) genotypes and C-allele compared with controls (p ? 0.0001, OR?=?5.1, 95% CI?=?2.7–9.7; p ? 0.0001, OR?=?3.5, 95% CI?=?2.1–6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p ? 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.