Genetic Variants of Serum Alpha 1 Antitrypsin

Complete absence of data on alpha 1 antitrypsin in this country prompted us to determine serum levels using radial immunodiffusion (RID) and phenotypes by isoelectric focusing (IEF) in 100 healthy adults (52 males and 48 females). Mean serum alpha 1 antitrypsin concentration in healthy subjects was 2.47±0.08 g/l and the main phenotypes MM (70%), M1 M2 (28%) and FM 3(2%) are infrequent in our population (JPMA 45:245,1995)

Serum Alpha 1 Antitrypsin and Pulmonary Emphysema

Using isoelectric focusing (lEE) and radial immunodiffusion (RID) techniques, serum samples from 100 normal healthy adults and 21 patients with pulmonary emphysema were analysed to identify varioud alpha 1 antitrypsin phenotypes and the Seru m concentrations,Ten percent of the patients had low serum values. The normal or most common genetic form, MM, is the predominant phenotype in both controls and patients (JPMA 46:102, 1996)

Phenotypes of Alpha 1 Antitrypsin in Karachi, Pakistan

Objective: To determine serum level of the protease inhibitor, to identify phenotypes and determine their frequencies. Study Design: A prospective study. Setting: PMRC Research Centre, JPMC and the Aga Khan University Hospital Karachi. Subjects: Healthy aduIts without history ol peptic ulcer disease and a normal endoscopy. Methodology: Quantitive measurement of serum alpha 1 AT was carried out by radial immunodiffusion. phenotyping by iso-electric focusing and confirmation of phenotypes by immunofixation and DNA analysis technique. Results:Serum alpha I AT was low in 13.4% of the subjects. Ni MM phenotype predominated followed by SZ SS, MZ and ZZ. DNA diagnosis accurately resolved the phenotypes as S and Z. Conclusion: Frequency by phenotype associated with total and intermediate deficiency is less in the populatio

Determination of Alpha-i Antitrypsin Genetic Deficiency in Duodenal Ulcer by Polymerase Chain Reaction

Objective: To confirm alpha-I-AT deficiency status in duodenal ulcer using a combination of PCR and restricted enzyme digestion. Methods: Fifty patients with endoscopically proven duodenal ulcer and hundred controls with no signs of the disease were included. Alpha-i-AT phenotypes were confirmed by polymerase chain reaction followed by restriction enzyme digestion. Results:Alpha-I-AT concentration in duodenal ulcer patients showed a mean value of 2.12 ± 0.11g/1 (range: 0.52-3.95 g/1, p Conclusion: Alpha-1 AT deficiency was found in 10% of duodenal ulcer patients. DNA analysis more accurately resolved the phenotypes as S and Z mutations (JPMA 52:545; 2002)

Methyl 4-eth­oxy-2-methyl-2H-1,2-benzothia­zine-3-carboxyl­ate 1,1-dioxide

In the crystal structure of the title compound, C13H15NO5S, the mol­ecules exhibit weak S=O⋯H—C and C=O⋯H—C inter­molecular inter­actions and arrange themselves into centrosymmetric dimers by means of π–π inter­actions (ring centroids are separated by 3.619 Å, while the closest C⋯C contacts are 3.514 Å). 1,2-Benzothia­zines of this kind have a range of biological activities and are used as medicines in the treatment of inflammation and rheumatoid arthritis

Genetic Markers and Duodenal Ulcer

Serum pepsinogen, ui-antitrypsin (ui-AT) and blood groups were studied as genetic markets in 32 patients with endoscopically proven duodenal ulcer and 44 control subjects with no family history of ulcer disease. Serum pepsinogen was detennined by the modified method of Edward et al7, a1-AT by single radial hnmunodiffusion8 (RID) and phenotyping was carried out by isoelectric focusing (IEF)9. Duodenal ulcer patients with hyper- pepsinogenemia (28%) and low serum ui-AT (35%) had a dominant blood group 0, lower mean age, an early onset of disease, a higher frequency of gastrointestinal (CI) bleeding and ulcer perforation. These parameters were found considerably different in patients with normal serum pepsi­nogen and ui-AT. Phenotype analysis of a1-AT revealed that four duodenal ulcer patients had partial deficiency of the protease inhibitor and none of the normal exhibited the deficiency pattern. The etiology of the disease appears to be genetic anomaly in 28% of patients while the rest (72%) had ulcers as a result of neuroendocrinological or environmental factors (JPMA 47:135,1997)

Ethyl 5-amino-1-(4-chloro-2-nitro­phen­yl)-1H-pyrazole-4-carboxyl­ate

In the mol­ecule of the title compound, C12H11ClN4O4, the pyrazole ring is coplanar with the amino and ethoxy­carbonyl groups within 0.026 (2) and 0.105 (2) Å, respectively. The C 6 ring of the 4-chloro-2-nitro­phenyl group is twisted by 53.58 (4)° relative to the plane of the pyrazole ring. The planar structure of the pyrazole ring is stabilized by an intra­molecular N—H⋯O hydrogen bond between its substituents. Neighbouring mol­ecules are linked through inter­molecular N—H⋯N and N—H⋯O hydrogen bonds, giving rise to one-dimensional tapes along the b axis. Mol­ecules in the chain are linked to those of an adjacent chain through weak C—H⋯O inter­actions, forming a three-dimensional network

Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri

Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiamoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size distribution with the average diameter of around 100 nm. Guanabenz and its noble metal nanoconjugates exhibited potent antiamoebic effects in the range of 2.5 to 100 μM against both amoebae. Nanoparticle conjugation enhanced the antiamoebic effects of guanabenz, as more potent activity was observed at a lower effective concentration (2.5 and 5 μM) compared to the drug alone. Moreover, encystation and excystation assays revealed that guanabenz inhibits the interconversion between the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were also observed. Notably, pretreatment of A. castellanii with guanabenz and its nanoconjugates exhibited a significant reduction in the host cell cytopathogenicity from 65% to 38% and 2% in case of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic evaluation of guanabenz and its nanoconjugates revealed negligible cytotoxicity against human cells. Guanabenz is already approved for hypertension and crosses the blood–brain barrier; the results of our current study suggest that guanabenz and its conjugated gold and silver nanoparticles can be repurposed as a potential drug for treating brain-eating amoebic infections