Plasma Neutrophil Elastase, α<Subscript>1</Subscript>-Antitrypsin, α<Subscript>2</Subscript>-Macroglobulin and Neutrophil Elastase–α<Subscript>1</Subscript>-Antitrypsin Complex Levels in patients with Dengue Fever

Dengue fever (DF) is characterized by systemic inflammatory response including neutrophil activation leading to uncontrolled elastase activity. This study was aimed to measure the activity of plasma neutrophil elastase (NE), its endogenous inhibitors α₁-antitrypsin (α₁-AT) and α₂-macroglobulin (α₂-MG) and elastase in complex with α₁-AT (NE–α₁-AT complex) in DF. 50 dengue patients [39 DF and 11 dengue hemorrhagic fever (DHF)] and 52 healthy subjects were included in the study. NE was measured using N-succinyl-tri-alanine-p-nitroanilide as substrate. α₁-AT, α₂-MG and NE–α₁-AT complex were estimated by ELISA. The result analysis indicated that the dengue patients had significantly higher elastase activity with significantly reduced inhibitor levels compared to controls. Between DF and DHF patients, DHF group had significantly higher elastase activity. In conclusion, significantly elevated NE and reduced inhibitors level in dengue fever indicate these parameters could be of significance in DF particularly for the assessment of progression of inflammatory processes.     

A Study on the Level of T<Subscript>3</Subscript>, T<Subscript>4</Subscript>, TSH and the Association of A/G Polymorphism with CTLA-4 Gene in Graves’ Hyperthyroidism among South Indian Population

Graves’ disease (GD) is an organ-specific heterogenous autoimmune disorder associated with T-lymphocyte abnormality affecting the thyroid, eyes and skin. GD is a multifactorial disease that develops as a result of complex interaction between genetic susceptibility genes and environmental factors. It has been suggested that the Cytotoxic T lymphocytes associated molecule-4 (CTLA-4) is a genetic susceptibility candidate for GD. The present study was focused on A/G polymorphism at position 49 in exon-1 of the CTLA-4 gene in 80 GD patients (GP) and 80 sex and age matched healthy individuals among South Indian (Madurai) population. Serum concentrations of thyroid hormone (T₄, T₃ and TSH) were determined by using automated analyzer. The genomic DNA was isolated from the patient and control groups and genotyping was performed using the polymerase chain reaction followed by restriction enzyme analysis using Bbv1. Significant difference (P < 0.001) was observed in the level of T₃, T₄ and TSH in GD patients and healthy individuals. The results revealed the CTLA-4 gene G/G genotype to be 32 (40%) in patients and 26 (32.50%) in healthy individuals, A/G genotype to be 37 (46.25%) in patients and 25 (31.25%) in healthy individuals and A/A genotype to be 11 (13.75%) in patients and 29 (36.25%) in healthy individuals. The calculated odds ratio (OR) in individuals with mutant genotype (GG/AG) reveal 3.6 fold risk for GD (95% confidence interval = 1.6–7.8). The mutant “G” allele frequency was observed to be 0.63 in GD patients and 0.48 in healthy individuals. Thus the present study demonstrates an association between the CTLA-4 gene polymorphism and Graves’ disease.     

Effect of Copper on <Emphasis Type="SmallCaps">l</Emphasis>-Cysteine/<Emphasis Type="SmallCaps">l</Emphasis>-Cystine Influx in Normal Human Erythrocytes and Erythrocytes of Wilson’s Disease

Wilson’s disease is a disease of abnormal copper metabolism in which free serum copper level is raised. The objective of the study was to determine, whether in Wilson disease, l-cysteine/l-cystine influx into RBC was decreased or not and the specific amino acid transporter affected by copper in normal human RBC. For l-cysteine/l-cystine influx, ten untreated cases, ten treated cases and ten age and sex matched healthy controls were recruited. To study the effect of copper on l-cysteine/l-cystine influx in RBC, 15 healthy subjects were selected. RBC GSH and l-cysteine/l-cystine influx were estimated by Beautler’s and Yildiz’s method respectively. In untreated cases, l-cysteine/l-cystine influx and erythrocyte GSH level were decreased showing that elevated level of free copper in serum or media decreased l-cysteine/l-cystine influx in human RBC. Copper treatment inhibited L amino acid transporter in normal RBC specifically.     

Coinheritance of Sicilian (δβ)<Superscript>0</Superscript>-Thalassemia and Two Rare Hemoglobin Variants: A Complex Case of Hemoglobinopathy

α-Thalassemia (α-thal) is considered as the most common inherited hemoglobin disorder worldwide. The present study describes the first observation of a combination of rare α-chain variants, and β-globin gene cluster deletion. A 21-year-old woman with thalassemia trait, marked microcytosis, mild anemia, and normal range of Hb F was referred to Amirkola genetic center in the North of Iran for routine molecular test of thalassemia in the context of carrier detection and prevention of thalassemia major birth. Nucleotide sequencing revealed a novel compound heterozygosity status for two non-deletional mutations on HBA2, Hb O Indonesia (α116(GH4)Glu → Lys), and Hb Matsue–Oki (α75 (EF4) Asp → Asn), together with heterozygosity for the sicilian (δβ)⁰-thal mutation. This finding highlights the necessity of deep molecular investigation of thalassemia in regions where thalassemia is abundant, and present highly heterogeneous population.     

Knowledge management in client–supplier relationship: emergent <Emphasis Type="Italic">vs</Emphasis> deliberate approach in small KIBS

It is often argued that small–medium enterprises (SMEs) do not manage knowledge the same way as large firms, but may need appropriate approaches to capture and exploit external knowledge effectively. This paper compares two opposite approaches to knowledge management (KM): one is called ‘deliberate’ or ‘planned’, and the other ‘emergent’. These approaches are analysed with reference to the management of knowledge pertaining to client–supplier relationships, which are particularly important in the case of small companies providing knowledge-intensive business services (KIBS). A case study of a small KIBS company is illustrated, which has developed two different projects, based on different approaches to KM, for managing knowledge referring to clients. The case shows that, for a small company, an emergent approach to KM can be more suitable than a deliberate one for managing such knowledge. The implications of this result for KM research and practice are then examined.     

Hypocalcemia in an 11 Year Old Child: <Emphasis Type="Italic">A Difficult Case to Treat</Emphasis>

Hypocalcemia is a laboratory and clinical abnormality that is observed especially in neonates and paediatric patients. Laboratory hypocalcaemia is often asymptomatic but it can manifest as central nervous system irritability, paraesthesia, tetany (i.e. contraction of hands, arms, feet, larynx, bronchioles), seizures, and even psychiatric changes in children. Cardiac function may also be impaired because of poor muscle contractility. We report a unique case of an eleven year old male child who presented with chronic kidney disease associated with severe hypocalcemia, tonic-clonic seizures, hypovitaminosis D but normal electroencephalogram and electrocardiography. The child required prolonged intravenous calcium gluconate therapy to correct his ionised calcium levels.     

Ameliorative Effects of <Emphasis Type="Italic">Allium sativum</Emphasis> Extract on iNOS Gene Expression and NO Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which is strongly associated with liver dysfunction. Hyperglycemia, through an oxidative stress pathway, damages various tissues. Herbal medicine is a good candidate to ameliorate hyperglycemia and oxidative stress. In this study, the effects of aqueous Allium sativum (garlic) extract (AGE) on gene expression of inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were evaluated in the liver tissue of diabetic rats. Four groups of rats contained normal control rats, garlic control rats (AGE), Streptozotocin (STZ) + nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic (DM + AGE). Glucose levels and liver enzymes activities were determined by colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO levels by Griess method, oxidative stress parameters by spectrophotometric method and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Glucose levels, activities of liver enzymes, oxidative stress markers, iNOS gene expression, and NO production increased significantly in diabetic rats in comparison with control rats, whereas after oral administration of garlic, these parameters decreased significantly, close to the normal levels. Hence, the beneficial effects of garlic on the liver injury of diabetes could be included in the hypoglycaemic and antioxidant properties of garlic via a decrease in gene expression of iNOS and subsequent NO production.     

A Pilot clinical study to evaluate the effect of <Emphasis Type="Italic">Emblica officinalis</Emphasis> extract (Amlamax™) on markers of systemic inflammation and dyslipidemia

Emblica officinalis Gaertn., commonly known as the Indian gooseberry or “Amla”, has been used as health food for centuries in India and other Asian countries. The biological effects of amla have been attributed to the antioxidant properties of the low-molecular weight hydrolysable tannins present in the fruit. Amlamax™ is a purified, standardized, dried extract of amla containing about 35% galloellagi tannins along with other hydrolysable tannins. Our earlier studies on rabbits showed significant reduction in total cholesterol and triglycerides as well as increase in HDL. The present study extends these results to human volunteers. Two doses of the extract were evaluated — 500 mg and 1000 mg per day for 6 months. Blood samples were collected at the 3rd and 6th months showed reduction in total and LDL cholesterols and enhancement of beneficial HDL cholesterol. In addition, blood CRP levels, a marker for inflammation, were also significantly reduced. Since dyslipidemia and inflammation are the two major components of cardiovascular diseases, the present results must be considered encouraging and indicate the potential of Amlamax™ in the management of heart diseases.