Glutamine fructose-6-phosphate amidotransferase (GFAT) gene expression and activity in patients with type 2 diabetes: inter-relationships with hyperglycaemia and oxidative stress

OBJECTIVE:: Cell culture and animal model studies have strongly suggested a role for the rate-limiting enzyme for hexosamine biosynthesis, glutamine:fructose-6-phosphate amidotransferase (GFAT) in insulin resistance. However, there are very few clinical studies and none on Asian Indians, a high-risk group for type 2 diabetes (T2DM), which examined the role of GFAT in insulin resistance and T2DM. DESIGN AND METHOD:: The study group comprised of T2DM subjects without any complications (n=25) and control non-diabetic subjects (n=23). GFAT mRNA expression and activity were measured by semi-quantitative RT-PCR and fluorimetry, respectively. Oxidative damage was assessed in plasma by the extent of lipid peroxidation [thiobarbituric acid reactive substances (TBARS)] and protein carbonyl content (PCO) using standard methods. RESULT:: The mean (+/-SE) GFAT activity was significantly higher in diabetic (30.22+/-2.40 pM/mg protein/min) compared to control subjects (20.10+/-1.12 pM/mg protein/min) (p<0.001). Plasma levels of diabetic patients also exhibited increased lipid peroxidation and protein carbonylation. GFAT activity was positively correlated (p<0.005) with GFAT mRNA, HbA(1c), insulin resistance (HOMA-IR), postprandial plasma glucose and levels of TBARS and PCO. In multiple logistic regression analysis, the association between GFAT activity and T2DM persisted even after adjusting for age, gender, BMI and HOMA-IR (OR=1.202, p=0.026). CONCLUSION:: Increased GFAT activity appears to be associated with insulin resistance, postprandial hyperglycaemia and oxidative stress in T2DM and may point towards a potential pathway amenable for therapeutic intervention.     

Fragile X premutation in a woman with cognitive impairment, tremor, and history of premature ovarian failure

Few women with Fragile X tremor ataxia syndrome (FXTAS) have been reported. They have milder manifestations at a later age than men. This gender difference may be related to the X inactivation pattern in women. We describe a woman who presented to her geriatrician with poor memory and was found to have ataxia and tremor. Additional queries yielded history of premature ovarian failure. Genetic testing showed heterozygous fragile X mental retardation gene premutation with 103 CGG repeats in the abnormal allele and 31 CGG repeats in the normal allele. Also, the X inactivation pattern was skewed with the active X chromosome predominantly having the premutation allele. We believe that FXTAS is more common in women than is generally thought and that many such patients masquerade as dementia of old age. Action tremor and ataxia associated with a history suggestive of premature ovarian failure should raise suspicions for FXTAS.     

A comprehensive screening analysis of antiphospholipid antibodies in Indian women with fetal loss

OBJECTIVE: The present study was aimed at a comprehensive analysis of acquired thrombophilia in a large series of Indian women with fetal loss. STUDY DESIGN: Four hundred and thirty women (median age 26 years, range 18-39 years) with unexplained fetal loss (median number of abortions 3, range 1-13) were screened for the presence of antiphospholipid antibodies (APA), i.e. lupus anticoagulant (LA), IgG/M antibodies for cardiolipin (ACA), beta 2 glycoprotein 1 (beta2 GP1) and annexin V. We also studied 100 normal healthy women (median age 24 years, range 18-30 years) who had at least one healthy child and did not have any miscarriage or other obstetric complications. RESULTS: The prevalence of persistently positive LA was 8.1% and 1% in the patients and controls, respectively (OR 8.7; 95% CI, 1.4-51; P<0.05). The overall prevalence of IgG and/or IgM antibodies for cardiolipin, beta 2 GP1 and annexin V were as follows-ACA 27.9% (OR 18.9; 95% CI, 5-70; P<0.05), beta 2 GP1 12.2% (OR 6.8; 95% CI, 1.8-25; P<0.05) and annexin V 14.6% (OR 17; 95% CI, 2.9-98; P<0.05). The conventional LA and ACA tests were positive 23.2% of the cases as against 1% in the controls (OR 14.8; 95% CI, 3.9-55; P<0.05). The prevalence of LA, ACA, beta 2 GP1 and annexin V antibodies as independent risk factors were observed in 0.5%, 16.5%, 5.4% and 7.8% in the patients as against 1% each in the controls. The overall positivity for any one of the APA studied was 42.6% (OR 10.2; 95% CI, 4.5-23; P<0.05). CONCLUSION: The present study thus indicates the importance of APA in women experiencing fetal loss where all the conventional causes of miscarriages have been ruled out. It also suggests that conventional APA assays (LA and ACA) are effective in the detection of a majority of APA positive cases and by the addition of other cofactor-dependent (beta 2 GP1 and annexin V) APA assays, there is a considerable increase in the diagnostic efficiency in the detection of APA.     

Successful radiofrequency catheter ablation of recurrent atrial fibrillation due to left inferior pulmonary vein tachycardia

This report illustrates the case of a young lady evaluated for drug-refractory symptomatic paroxysmal atrial fibrillation. Successful isolation of left inferior pulmonary vein was achieved by segmental ostial ablation and circumferential Lasso mapping catheter. Patient is now free of symptoms and is off all anti-arrhythmic drugs.     

Hypersensitivity pneumonitis in children: clinical features, diagnosis, and treatment

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a form of immune-mediated inflammatory lung disease involving the distal portions of the lungs associated with intense or repeated exposure to a variety of finely dispersed environmental antigens. Although once believed to be a disease of adults because of its frequent association with the occupational setting, HP exists in the pediatric population and often goes unrecognized. Childhood HP is often associated with exposure to antigens in the home environment as well as with certain hobbies.Patients present in any one of the three disease stages: acute, subacute, and chronic, all with unique clinical presentations. Histopathologic findings depend on the disease stage at the time of evaluation. The immuno-pathogenesis is complex, but immune-complex (type III hypersensitivity) and cell-mediated (type IV hypersensitivity) immune responses appear to be the primary immune mechanisms involved in the pathogenesis of HP. Diagnosis can be very challenging. Although no single diagnostic or clinical laboratory test is available to diagnose HP, the most significant diagnostic tool is a detailed environmental exposure history. Avoidance of the inciting antigen is the most important form of treatment. Acute HP is responsive to antigen removal alone. However, a short course of prednisone for 2-3 weeks can be useful in patients with severe attacks. Subacute and chronic HP may require higher doses of corticosteroids for a longer duration (i.e. months); however, the long-term efficacy of using corticosteroids is still not well defined. As with most hypersensitivity diseases, early diagnosis provides the best prognosis.     

Bladder wall lipoma

Bladder wall lipoma is a rare finding that includes mature, well-encapsulated fatty tissue within the submucosa of the bladder wall. We present a case of a submucosal bladder wall lipoma that was discovered incidentally during a workup for microhematuria. This lesion was seen during cystoscopy and removed using cold cup biopsy forceps. This lipoma should be differentiated from pelvic lipomatosis in that it was confined to the submucosa of the bladder wall and did not cause compression of the pelvic viscera or its structures.