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The composition of carboxylic acids of the rhizomes of Iris carthaliniae and Iris medwedewii by the gas chromatography - mass spectrometry method has been studied for the first time. The total content of carboxylic acids for I. carthaliniae was 1.34%, including (%) - 0.65 fatty; 0.36 mono-, di- and tri-carboxylic; 0.33 phenol carboxylic acids. The yield of carboxylic acids for I. medwedewii was 1.58%, including (%) - 0.73 fatty; 0.38 mono-, di- and tri-carboxylic; 0.47 phenol carboxylic acids. The dominant fatty acids in the rhizomes of I. carthaliniae were myristic acid (25%), palmitic acid (14.41%), stearic acid (10.51%) and linoleic acid (6.05%). Besides, levulinic acid (15.84%) and oxalic acid (4.42%) prevailed among organic acids, while ferulic acid (2.43%), citric acid (1.88%) and malic acid (3.62%) prevailed among the hydroxy acids. The fatty acids palmitic acid (6.51%), linoleic acid (8.38%), oleic acid (3.87%) and capric acid (3.21%) were found in the rhizomes of I. medwedewii, and also, levulinic (29.39%), malonic (1.45%), succinic (1.72%) acids prevailed among the organic acids and citric (25.37%), malic (3.30%) and ferulic (2.42%) acids in the rhizomes of I. medwedewii prevailed among the hydroxy acids.Key words: Iris carthaliniae Iris medwedewii rhizomes carboxylic acids GC-MS analysis.

Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system. Our nicotine vaccine candidate was administered intranasally using the Neisseria meningitidis serogroup B Adjuvant Finlay Proteoliposome 1 (AFPL1) as a part of the delivery system. This system was designed to generate a robust immune response by stimulating IL-1β production through Toll-like receptor 4 (TLR4), a potent mechanism for mucosal immunity. The vaccine induced high antibody titers in mice sera in addition to inducing mucosal antibodies. The efficacy of our vaccine was demonstrated using in vivo challenge experiments with radioactive [(3)H]-nicotine, followed by an analysis of nicotine distribution in the lung, liver, blood and brain. Our results were encouraging as the nicotine concentration in the brain tissue of mice vaccinated with our candidate vaccine was four times lower than in non-vaccinated controls; suggesting that the anti-nicotine antibodies were able to block nicotine from crossing the blood brain barrier. In summary, we have developed a novel nicotine vaccine for the treatment of tobacco addiction by intranasal administration and also demonstrated that the AFPL1 can be used as a potential adjuvant for this vaccine design.

β-Adrenergic receptor antagonists (β-blockers) have been recognized for their cardioprotective properties, prompting use of these pharmacologic agents to become more mainstream in acute myocardial infarction (AMI) and congestive heart failure (CHF). Despite their popularity as a class, the ability to protect the myocardium varies significantly between different agents. Carvedilol is a non-selective β-blocker with α₁-adrenergic receptor antagonism properties. It is unique among β-blockers because in addition to improving exercise tolerance and its anti-ischemic properties secondary to a reduction in heart rate and myocardial contractility, carvedilol exerts other beneficial effects including: antioxidant effects; reduction in neutrophil infiltration; apoptosis inhibition; reduction of vascular smooth muscle migration; and improvement of myocardial remodeling post-AMI. These properties, documented in animal models and subsequent clinical trials, are consistent with established evidence demonstrating decreased morbidity and mortality in patients with CHF and post-AMI. This article reviews the role of carvedilol compared with other β-blockers in the treatment of CHF and post-AMI management.

Camelid single domain antibodies fused to noncamelid Fc regions, also called chimeric heavy chain antibodies (cHCAb), offer great potential as therapeutic and diagnostic candidates due to their relatively small size (80 kDa) and intact Fc. In this chapter, we describe two approaches, limiting dilution and minipools, for generating nonamplified Chinese hamster ovary cell lines stably expressing cHCAb in suspension and serum-free cultures using a stringent antibiotic selection. Neither of the protocols necessitates the acquisition or implementation of expensive automated infrastructures and thus could be applied in any lab with minimal cell culture setup. The given protocol allows the isolation of stable clones capable of generating up to 100 mg/L of antibody in batch mode performed in shaker flasks.

Carcinoembryonic antigen related cell adhesion molecule (CEACAM) 6 is over-expressed in different types of cancer cells. In addition, it has also been implicated in some infectious diseases. Targeting this molecule by an antibody might have applications in diverse tumor models. Single domain antibody (sdAb) is becoming very useful format in antibody engineering as potential tools for treating acute and chronic disease conditions such as cancer for both diagnostic as well as therapeutic application. Generally, sdAbs with good affinity are isolated from an immune library. Discovery of a new target antigen would require a new immunization with purified antigen which is not always easy. In this study, we have isolated, by phage display, an sdAb against CEACAM6 with an affinity of 5 nM from a llama immunized with cancer cells. The antibody has good biophysical properties, and it binds to the cells expressing the target antigen. Furthermore, it reduces cancer cells proliferation in vitro and shows an excellent tumor targeting in vivo. This sdAb could be useful in diagnosis as well as therapy of CEACAM6 expressing tumors. Finally, we envisage it would be feasible to isolate good sdAbs against other interesting tumor associated antigens from this library. Therefore, this immunization method could be a general strategy for isolating sdAbs against any surface antigen without immunizing the animal with the antigen of interest each time., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Inflammatory bowel disease (IBD) is a chronic disease that affects not only the young adults, but also the elderly. The elderly are more vulnerable and at higher risk from complications related to IBD. In this review we focus on IBD important features in the elderly and discuss the disease (1) epidemiology, (2) pathophysiology, (3) clinical manifestations and diagnosis, (4) prognosis, (6) therapy and (7) potential future research directions.

1. Hypertensive mice expressing the human renin (REN) and angiotensinogen (AGT) genes are used as a model for human hypertension. 2. The aim of the present study was to investigate the cellular expression and distribution of inducible nitric oxide synthase (iNOS) using immunohistochemistry in lung, heart and kidney tissues from a model of human hypertension using male and female double-transgenic (h-Ang 204/1h-Ren6) mice and wild-type C57/BI6J mice as controls. 3. In the kidney, the pattern of iNOS expression in various renal microanatomical regions during hypertension was similar to that of age-matched controls, except in the medullary ascending limb (MAL). In hypertension, iNOS expression was downregulated in the MAL. No significant differences in iNOS expression were seen between control or hypertensive mice in various cardiac microanatomical locations. In the lungs of hypertensive mice, iNOS expression was upregulated in bronchial airway epithelium and bronchial and vascular smooth muscle cells, but downregulated in alveolar macrophages, alveolar septa and pulmonary vascular endothelial cells. Expression of iNOS was similar between male and female mice in the kidney, heart and lungs. 4. In conclusion, iNOS regulation in hypertension is complex and depends on the cell type in which it is expressed and the localization of the cell type in the cardiorenal and pulmonary systems.

Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular dysfunction and symptoms of heart failure occur in the peripartum period in previously healthy women. Incidence of PPCM ranges from 1 in 1300 to 1 in 15,000 pregnancies. The etiology of PPCM is unknown, but viral, autoimmune, and idiopathic causes may contribute. The diagnostic criteria are onset of heart failure in the last month of pregnancy or in first 5 months postpartum, absence of determinable cause for cardiac failure, and absence of a demonstrable heart disease before the last month of pregnancy. Risk factors for PPCM include advanced maternal age, multiparity, African race, twinning, gestational hypertension, and long-term tocolysis. The clinical presentation of patients with PPCM is similar to that of patients with dilated cardiomyopathy. Early diagnosis and initiation of treatment are essential to optimize pregnancy outcome. Treatment is similar to medical therapy for other forms of dilated cardiomyopathy. About half the patients of PPCM recover without complications. The prognosis is poor in patients with persistent cardiomyopathy. Persistence of disease after 6 months indicates irreversible cardiomyopathy and portends worse survival.

Intussusception is a common complication after canine hematopoietic cell transplantation (HCT). The present study was undertaken to evaluate predisposing factors of intussusception and to test whether intussusception can be managed surgically during the period immediately after HCT. We determined the incidence of intussusception after HCT was performed in 325 canine recipients (autologous, n = 43; allogeneic, n = 282) during the interval from January 2002 to May 2005. Intussusception was diagnosed in 16 of 325 dogs (4.9%). Intussusception was not significantly associated with the dose of irradiation, source of hematopoietic graft, use of immunosuppressive agents, gender, or age at transplant. A group of 9 of the affected dogs underwent small-bowel resection after diagnosis, and 7 were managed without surgical intervention. Despite complicating factors such as gastrointestinal toxicity and low neutrophil and platelet counts induced by the marrow conditioning regimen and the use of immunosuppressive agents, successful surgical management of intussusception was achieved in 6 of 9 dogs, as compared with successful management of 0 of 7 without surgery. Intussusception did not recur after surgical intervention in any dog. Recent HCT and post-transplant immunosuppressive therapy are not absolute contraindications to surgical intervention for intussusception in canine recipients of HCT.

Objective: To describe the patterns of ocular trauma, cause of injury and its effects on eye., Design: A retrospective case series., Place and Duration of Study: Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, from January 1999 to June 2004., Patients and Methods: Medical records of 1105 patients admitted with ocular trauma were reviewed. The details of patients regarding age, gender, literacy, cause of injury and its effects on eye were entered into specially-designed performa. Sample selection consisted of all patients with history of ocular trauma and who were admitted to hospital. Population details consisted patients who were referred to the hospital from all parts of N.W.F.P. Thus, the frequency of trauma in the hospital admissions was analysed., Results: Ophthalmic trauma comprised 6.78% of the hospital admission. One thousand one hundred and five patients presented with eye injuries. Out of them, 21 patients suffered from trauma to both eyes. Almost 80% patients were male and 69% patients were below 30 years of age. Delayed presentation was more common and 63.61% patients presented after one week. Open globe injuries were more common [520 eyes (46.18%)] than closed globe injuries [484 eyes (42.98%)]. 23.26% of open globe injuries were associated with intraocular and intra-orbital foreign bodies. Superficial non-perforating, eyelid and adnexal and burns were seen in 122 eyes (10.83%). Among the complications, lens damage and hyphema was seen in more than 50% of the patients, 16.60% eyes were infected at the time of admission and 4.88% of eyes needed enucleation or evisceration. The common causes of injury were violence in 37.37%, occupational in 24.43% and domestic accidents in 19.18%., Conclusion: Ophthalmic trauma is a major public health problem. Majority of the involved are male and under 30 years of age. Delayed presentation is more common. Open globe injuries are more frequent. Violence and occupational injuries are the major causes.

Intravenous injection of a cartilage proteoglycan (aggrecan)-specific Th1 hybridoma clone 5/4E8 induced joint lesions similar to those seen in either primary or adoptively transferred arthritis in BALB/c mice. A sister clone, TA20, recognizing the same peptide epitope of human aggrecan and using the same Vbeta4 and Valpha1 segments, failed to induce joint inflammation. This study examines the fine epitope specificities of these two clones. Both 5/4E8 and TA20 hybridomas were generated using T cells from the same arthritic animal that has been immunized with human aggrecan, and both clones recognized peptides containing a consensus GRVRVNSAY sequence. However, flanking regions outside this nonapeptide sequence region had differential impact on peptide recognition by the two clones. Similarly, when single amino acid substitutions were introduced to the consensus sequence, significant differences were detected in the epitope recognition patterns of the T cell hybridomas. The 5/4E8 hybridoma showed greater flexibility in recognition, including a higher responsiveness to the corresponding self (mouse) aggrecan peptide, and produced more inflammatory cytokines (IFN-gamma and TNF-alpha), whereas hybridoma TA20 produced IL-5 in response to either human or mouse self peptide stimulation. These results demonstrate that, within the pool of immunodominant (foreign) peptide-activated lymphocytes, marked individual differences of degeneracy exist in T cell recognition, with possible implications to autopathogenic T cell functions.

The effects of nisin on lactate accumulation, growth, and Fe(III) binding by Bifidobacterium thermophilum (ATCC 25866) and Bifidobacterium breve (ATCC 15700) were investigated. Nisin inhibited lactate production by B. thermophilum at concentrations of less than 1 microg/ml, but this effect could be largely eliminated by pretreatment of the organism with 100 to 400 microM Al(III) or La(III). Nisin also inhibited the growth of B. thermophilum at concentrations of 2 to 3 microg/ml, with lower concentrations showing lag periods and/or slower rates of growth. However, Al(III) could not negate these effects, most likely because of Al(III) chelation by the trypticase-proteose-yeast extract medium. Nisin was able to increase instantaneous Fe(III) binding by both B. thermophilum and B. breve, though prolonged-time experiments (up to 120 min) with B. thermophilum indicated no difference in total Fe(III) bound. Nisin was thus able to increase the free radical reaction rate with bifidobacteria and the resultant rate of Fe(III) binding. It was concluded that nisin will normally inhibit the metabolic activity of B. thermophilum along with that of certain bacterial pathogens; however, this effect may in some instances, be abated by a pretreatment with Al(III). Moreover, by accelerating free radical action and the binding of iron by bifidobacteria, nisin may be able to potentiate their normal probiotic action.

1. Previous reports indirectly implicate a neural mechanism for coronary constriction to centrally administered digitalis. However, autoregulatory changes in coronary resistance due to changes in arterial pressure may have influenced the interpretation of these studies. 2. We tested directly the hypothesis that cardiac sympathetic innervation is responsible for coronary constriction to ouabain by examining the effects of ouabain (intravenous (i.v.) and intracerebroventricular (i.c.v.)) before and after bilateral stellate ganglionectomy. 3. Cats were anaesthetized and instrumented for the measurement of heart rate, blood pressure and coronary blood flow velocity using an epicardial-attached suction Doppler probe. Animals were treated with atenolol and the effects of either i.v. or i.c.v. injections of ouabain were examined. 4. In seven cats treated with atenolol, i.v. ouabain (0.11 mg/kg) produced maximal increases in arterial pressure and coronary vascular resistance index (CVRI) of 66 +/- 7 mmHg and 37 +/- 9%, respectively. Following bilateral stellate ganglionectomy (n = 7), ouabain produced similar increases in arterial pressure (70 +/- 9 mmHg) and CVRI (39 +/- 7%). A higher dose of i.v. ouabain (1.1 mg/kg) produced maximal increases in arterial pressure (115 +/- 4 mmHg) and coronary resistance (86 +/- 14%) in intact cats (n = 6) that were similar to responses seen in cats in which stellate ganglionectomy had been performed (n = 6; arterial pressure 104 +/- 13 mmHg; coronary resistance 114 +/- 6%). The increases in coronary resistance to ouabain at both doses were significantly greater than increases in coronary resistance to passive elevation of arterial pressure during aortic constriction. Thus, autoregulation does not explain fully the coronary constriction to ouabain. 5. To further examine a central mechanism, i.c.v. perfusion with 0.3 mmol/L ouabain was performed in six cats, resulting in increases in arterial pressure (122 +/- 7 mmHg) and coronary resistance (58 +/- 14%). Similar increases in arterial pressure (117 +/- 16%) and coronary resistance (84 +/- 20%) were seen in separate studies (n = 6) following stellate ganglionectomy. 6. These results indicate that coronary constriction to ouabain does not require intact cardiac sympathetic innervation, but probably involves a direct or humorally mediated effect.

Eight-three fungal isolates collected and cultured from the air spora of damp public sector Scottish housing have been screened for cytotoxic properties. A bioassay procedure has been utilised for this purpose involving cytotoxic effects on human embryonic diploid fibroblast lung cells grown as monolayer cultures within the wells of microtitre plates. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] biochemical assay system employed has revealed that 39 (47%) of the moulds investigated possessed spore-associated cytotoxic properties; a value which emphasises the potential health hazards of the continual inhalation of toxigenic fungal propagules by occupants of mouldy houses. Penicillia, the most prevalent fungi found in the internal atmosphere of the domestic environment, accounted for the great majority of cytotoxic strains identified.