A. R. Dehpour, PharmD, PhD
A. Javadian, MD
Vol 56, No 3 (2018)
Tri-functional antibodies, as an effective novel tumor targeting agents, are composed of anti-CD3 rat IgG2b and an anti-tumor antigen antibody. We have intended to develop a novel drug system to induce the apoptosis of HER2-expressing tumor cells, activate and engage cytotoxic T lymphocytes, natural killer cells, and macrophages. In addition, the drug can inhibit programmed death ligand 1 (PDL-1)-expressing tumor cells. We have designed a mammalian vector system suitable to express the trifunctional antibody composed of antiHER2×human-CD80: human-IgG1Fc antibody. This antibody contains four chains of anti-HER2/CL, anti-HER2/CH1-3, B7.1/CL, and B7.1/CH1-3 within the human IgG1 framework and so the vector system will simultaneously express the four chains. The amino acid/nucleotide sequences datasets were retrieved from the GenBank, UniProtKB and PDB databases. The heavy and light chains variable domain framework regions and complementarity determining regions of scA21 antibody were determined by IMGT/V-QUEST and Paratome software. The amino acid sequences of tri-functional antibody chains manually were assembled and converted to DNA sequences by sequence manipulation suite software. The adapting codon usage of these DNA sequences was performed by JCAT software. Finally, the secondary structures of obtained RNAs from the DNAs were individually analyzed by RNAfold program. The Prodigy equilibrium dissociation constant, a ratio of koff/kon, between the antibody and its antigen for hantiHER2VHCH-HER2, hantiHER2VLCL-HER2, CD80CH-CD28, and CD80CL-CD28 were equal to 3.60E-10, 3.10E-9, 1.10E-8 and 2.70E-10; respectively. These findings were confirmed the composition and nano-molar affinity of the respective constructs. A single specific no-cloning expression vector, pHuchiTriomAb, was designed in silico with a desirable length of 8.292 Kbps and bidirectional expression potential for the four chimeric antibody chains. This construct was designed, and gene codon usage adapted to be expressed within CHO cells and secreted a trifunctional antibody into the cell culture medium by interleukin 21 signal peptide.This robust expression system for rapid production of tri-functional antibody has been designed to substitute hybrid hybridoma technology (quadroma and trioma) with the facilitated purification of the trifunctional antibody from the antibody variants.
One of the most frequent complications of diabetes is diabetic peripheral neuropathy. Hyperglycemia would result in the advancement of this condition over a period of time. The most effective way in preventing diabetic neuropathy is regular control of glucose. In this study; we evaluated the effects of lithium onstreptozocin (STZ)-induced diabetic neuropathy in rats. Diabetic neuropathy was created 7 weeks after administration of STZ (45 mg/kg). Lithium was added to drinking water (450 mg/l) for 7 weeks and its plasma level after this period of time was 0.17±0.02 mmol/l. Levels of adenosine triphosphate (ATP) in dorsal root ganglion (DRG) neurons, oxidative stress parameters, open-field activity test and morphological analysis were assessed in this investigation. Currentresults showed significant elevation of oxidative stress biomarkers, reduction of ATP, abnormal morphology of DRG neurons and decrease of total distance moved in rats with STZ-induced diabetic neuropathy. The alterations in mentioned parameters were considerably restored by lithium treatment. These findings provide evidence for protective effects of lithium on STZ-induced diabetic neuropathy.
Colorectal cancer (CRC) is one of the most prevalent cancers in the world. The p53 protein is the most commonly mutated protein in human cancer, and it is a frequent abnormality in colorectal cancers. In this study, we evaluated the expression of p53 protein and its association with clinicopathological findings as prognostic factors and mortality rate in 95 colorectal cancer patients’ in Northeast Iran, over a 5 years period (2010-2015). In this retrospective study, the method of immunohistochemistry (IHC) was applied to determine the expression of the p53 protein and pathological features of tumors and mortality rate were examined between 2010 and 2015 at Gorgan City (IRAN). Multiple logistic regression models were used to estimate odds ratios and confidence intervals between clinicopathological and mortality rate as the outcome variable, adjusted for potential confounders. Immunoreactivity was found in 58.9% of specimens from 95 patients with colorectal cancer, and the mortality rate was estimated 14.7 percent. The mortality rate of patients with colorectal cancer is significant, and findings indicate that it relates to pathologic factors such as vascular involvement [OR=0.02, CI95%: 0.006-0.11], lymph node involvement [OR=0.17, CI95%: 0.05-0.56], round neural invasion, depth of invasion, tumor size and grade. The findings confirmed that the P53 gene mutation could be considered as a prognostic factor affecting mortality in cancer and specifically colorectal cancer. Although the P53 protein expression shows no relationship with histopathological features, the mortality rate of the patients demonstrated a strong association.
The increased risk for developing loss of bone density in patients with hemophilia has been recently regarded. The present study was conducted to compare the levels of vitamin D and other biochemical factors affecting bone turnover in patients with hemophilia and those without this problem. The study participants were stratified into the following subgroups 1) the hemophilic patients without evidence of viral infections, 2) those with the healthy condition without evidence of infection by the viral infections. All subjects were asked to take venous blood sample to assess the levels of serum biomarkers related to bone metabolism and turnover. Comparison of different biochemical markers related to bone metabolism and turnover showed significantly lower free testosterone, total testosterone, thyroid stimulating hormone (TSH), vitamin D, calcium, osteocalcin, calcitonin, and parathormone levels as well as higher serum alkaline phosphatase, Serum C-telopeptide (CTX), and N-terminal telopeptide (NTx) levels in those hemophilic patients as compared to control group. Hemophilia can adversely affect bone structure leading to bone loss in hemophilic patients. An appropriate screening protocol pertaining to osteoporosis must be implemented in the facilities for hemophiliac patients, so that preventive and healthcare measures like more physical activity and consumption of vitamin D and calcium supplements could be provided.
The purpose of the study was to determine clinical outcomes of Descemet Membrane Endothelial Keratoplasty (DMEK) in patients with Pseudophakic Bullous Keratopathy (PBK). The study was conducted at a tertiary referral center. This was a retrospective case series. Pseudophakic eyes having undergone DMEK surgery for Pseudophakic Bullous Keratopathy was considered the object of study. The examination implied the analysis of best corrected visual acuity (BCVA or CDVA), endothelial cell density (ECD), intraocular pressure (IOP), intraoperative and postoperative complications and a follow-up in 1, 3, and 6 months. For the purposes of the study, 25 pseudophakic eyes with PBK were examined. One month after the surgery patients reached a BCVA of 0.49±0.08(M±SD), after 3 months - BCVA of 0.65±0.12(M±SD), and a BCVA of 0.78±0.17 (M±SD) in the last follow-up in 6 months after the surgery (P<0,001). The mean ECD after one month was 1661±133 (M±SD) cells/mm2, after 3 months - 1591±124 (M±SD) cells/mm2, and during the last control in 6 months -1579±128 (M±SD) cells/mm2. The graft detachment rate was 12% (3 cases). Hypertension was observed in one eye (4%), necessitating partial air elimination through a corneal wound within the first hours after the surgery. DMEK may give excellent visual results in Pseudophakic eyes without increasing the risk of complications when compared to Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) and Penetrating Keratoplasty (PKP). Anatomic repair after DMEK is associated with improved corneal clarity and BCVA.
Recently prevention of HIV transmission from mother to child by antiretroviral regimens has resulted in growing the numbers of HIV exposed but uninfected children (HIV-EU). The aim of present study was evaluation of growth and neurodevelopment status among less than 2-year-old HIV exposed uninfected children. A cohort study was carried out at Vali-e-Asr Hospital (Tehran-Iran). Thirty-nine HIV-EU neonates were recruited (2014 to 2016). Neonates and infants with concern to growth and neurodevelopment status were evaluated at 6, 12, 18, and 24 months by an expert physician. Neurodevelopment assessment was based on WHO Milestones Chart and Age and Stage Questionnaire. Of all children, 22 were male, and 17 were female. Regarding growth indices, although mean birth weight in half of the neonates was lower than normal population; no postnatal descending trend was observed in their growth chart. No significant differences were found between two groups' height and head circumference. Among the neurodevelopmental parameters measured, in 6th months of life, 2 cases had abnormality in the gross motor while at 12 months, 6 cases had delay in language, social problem, and motor disorders. At 18 and 24 months, 7 infants showed developmental problems of which 71.4% of their mothers were younger than others (age<25 years, P=0.009). Prevalence of neurodevelopmental disorders including delay in language, motor, and social domains was common among HIV-EU children. As several environmental factors may involve the etiology of neurodevelopmental disorders, nearly-full postnatal control and prevention seem necessary.
According to previous studies in patients with Coronary artery disease (CAD), it is important to consider both medical conditions and psychological factors such as illness perceptions to explain differences in Health-Related Quality of Life (HRQoL). Patient’s illness perception is formed based on Patient’s beliefs and perceived information about their conditions, presumably influencing the individual’s mental health and how the patients deal with the medical conditions. The objective of this study was to analyze the relationship between illness perception and quality of life in patients with CAD. In this cross-sectional study, 99 CAD patients filled out questionnaires, including the brief illness perception questionnaire, the Health-related quality of life scale (SF36). The data were analyzed using multiple linear regression.When corrected for confounders, identity (β=−0.47) was associated with Physical Component (PCS). Identity and age explained 53% of the variation in PCS (R2=0.53). Personal control (β=0.20), identity (β=−0.23) and Emotional response (β=−0.25) were associated with Mental Component (MCS). They explained 47% of the variation in the Mental Component (R2=0.47) domain. This study showed that there is a relationship between illness perception and quality of life in patients with CAD. Better HRQoL was found in patients who have a better understanding of the disease, experience better personal control, and have less of a physical and mental response. Results from this study provide starting points for the development of interventions focusing on illness perceptions to support CAD patients in their disease management and to improve HRQoL.
Metabolic syndrome is a cluster of conditions which enhance the risk of metabolic and cardiovascular diseases such as diabetes mellitus, dyslipidemia, or hypertension. Obesity plays a pivotal role in the pathogenesis of metabolic syndrome. French maritime Pine bark extract (PBE) in addition to its antioxidant properties, has protective effects on metabolic syndrome component through several mechanisms. At present, there are few data on the net impact of PBE on metabolic syndrome factors in obesity. This trial report the results of 2-month period supplementation of 38 obese women received weight loss diet and PBE (150mg/day) or placebo. The metabolic syndrome parameters and body composition were assessed at the beginning and end of the study. The results showed PBE has significant protective effects on metabolic syndrome factors including central obesity, TG, HDL, BP and FBS (P<0.05), decrease metabolic syndrome risk in obesity and improve body composition. Thus, The PBE is considered as a new approach to obesity and metabolic syndrome prevention.
Breast plasmacytoma is a rare neoplasm. Here we present a case of extramedullary plasmacytoma of the breast in a 41-year-old Iranian lady who was a known case of spine plasmacytoma. Two years ago study case was presented with severe back pain. At that time, MRI revealed an expansile and destructive lesion in the body of S1 which was suggestive of metastasis. The patient underwent incisional biopsy that was a representative of a plasmacytoma. Skeletal survey, bone marrow aspiration, and serum protein electrophoresis were negative. The patient received radiation therapy. This year (2 years later) she detected a mass in her right breast. A mammography revealed a 30 mm high-density mass with an ill-defined border in the right breast. The mass was excised, and histological examination confirmed the diagnosis of plasmacytoma. Although plasmacytoma of the breast is rare, this tumor should be considered as a differential diagnosis of a breast mass, especially in patients with plasma cell dyscrasias.
Vascular access for dialysis is essential for these patients with end-stage renal disease, improvements in hemodialysis managment have lead to extended life expectancy. The creation and maintenance of hemoaccess occupies a significant portion of most vascular and general surgery practices.Venous hypertension due to arteriovenous fistula is usually secondary to venous outlet obstruction. Side to side proximal artery arteriovenous fistula serves as a certain cause of hemodialysis, but it is rarely reported as a peripheral venous hypertension cause. We are reporting a case with developed venous hypertension having dermal injuries in the arm. The patient underwent successful side-to-side radio cephalic fistula creation in the snuffbox a year ago.
Here we report a case of postoperative thrombocytopenia (TTP) in a 77-year-old case that has been undergoing mitral valve replacement with combined coronary artery bypass grafting. In the 5th days of operation, his platelet count was reduced and despite platelet transfusion, his platelet count reaches to a minimum level of 15000 µg/mL on the 34th day of surgery. Despite platelet transfusion and plasmapheresis, platelet count continues to decrease and signs and symptoms of disseminated intravascular coagulation appeared by unexpectable renal and pulmonary bleeding. Finally high dose, steroid therapy was started and after some days, platelets count raised to 80000 µg/mL. DIC was recovered, but acute renal failure did not respond to medical and hemodialysis and the case expired with sudden cardiac arrest and ventricular fibrillation.we conclude that if the diagnosis of TTP was made earlier in the course of disease by consulting internist and steroids was instituted it might prevent ARF and its poor outcome.
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