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Biomedical subjects

George Alexander

Publications and source records attributed to George Alexander.

17 recordsLinked to original sources
PubMed2006

Lutein effect on retina and hippocampus of diabetic mice.

Oxidative stress markers and functional tests were studied to confirm early biochemical and functional changes in retina and hippocampus of diabetic mice. The effects of lutein treatment were also tested. Mice were induced diabetic by alloxan injection and divided into subgroups: control, control+lutein, diabetic, diabetic+lutein, diabetic+insulin, and diabetic+insulin+lutein. Treatments started on Day 4 after alloxan injection and animals were sacrificed on Day 14. Malondialdehyde and glutathione concentrations and glutathione peroxidase activity were measured as oxidative stress markers. The following functional tests for retina and hippocampus were performed: electroretinogram and Morris water maze test. NFkappaB activity was also measured. Oxidative stress and NFkappaB activity increase in the retina and hippocampus after 15 days of diabetes. Impairment of the electroretinogram and a correlation between latencies of the water maze test and glycated hemoglobin (HbA1c) levels were observed. Lutein prevented all these changes even under hyperglycemic conditions. Retina appears to be affected earlier than hippocampus by diabetes-induced oxidative stress. Although a proper glycemic control is desirable in preventing the development of diabetic complications, it is not sufficient to prevent them completely. Lutein could be an appropriate coadjuvant treatment for the changes observed in this study.

Animals↗
PubMed2006

Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is commonly associated with overweight and insulin resistance. Aerobic exercise is known to reduce insulin resistance. We studied the effect of regular aerobic exercise on serum aminotransferase levels in patients with NASH. METHODS: Sixty-five (mean age 38.7+/-9.5 years; 46 [78%] males) out of 94 patients diagnosed with NASH participated in the study. Each patient was advised regular aerobic exercise for 30 min duration per day, and trained to achieve a heart rate of 60-70% of his/her maximal heart rate for at least 5 days a week. In addition, those with a high body mass index (BMI) were advised a moderately energy-restricted diet. Patients were followed up monthly for at least 3 months by BMI, waist-hip ratio (WHR), waist circumference (WC), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: Forty-three (72.8%) patients had a high BMI. Central obesity (WHR >or=0.90 cm in men and >or=0.85 cm in women) was present in 58 (98.3%) patients and metabolic syndrome in 12 (20.3%) patients. In the 44 patients who complied regularly with the exercise program, serum ALT normalized in 20 (45%; P<0.05), and mean AST and ALT values declined from 70.5 and 104.0-41.5 (P<0.001) and 63.2 (P<0.001), respectively. Overweight patients lost a mean 3.1 kg (range 0-13 kg) weight and showed a decline in BMI (28.7 vs 27.5; P<0.001) and WC (99.4 cm vs 96.1 cm; P=0.001). Serum ALT did not normalize in any of the 15 patients who failed to comply with the exercise program; their pre- and post-AST (82.8 and 81.2, respectively) and ALT (98.0 and 96.1, respectively) levels, BMI (27.5 and 27.6, respectively) and WHR (0.99 cm and 0.99 cm, respectively) did not show any significant change at 3 months, and also for an extended mean follow-up period of 5.3 months. CONCLUSION: Moderate intensity aerobic exercise helps in normalizing ALT levels in patients with NASH.

Adult↗
PubMed2005

Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

Animals↗
PubMed2005

High rates of early HBeAg seroconversion and relapse in Indian patients of chronic hepatitis B treated with Lamivudine: results of an open labeled trial.

BACKGROUND: The use of Lamivudine in chronic hepatitis B (CHB) is well known, however the reported rate of HBeAg sero-conversion and its durability post-treatment have varied considerably. We undertook the present study to study the effect of Lamivudine on HBeAg loss and seroconversion rates in Indian patients of CHB in relation to frequency, predictors and durability. METHODS: We treated 60 patients of e antigen positive CHB (with active viral replication and ongoing necro-inflammatory activity) with Lamivudine. They were followed up by monthly aminotransferases, and 3 monthly HBeAg and anti-HBe. Those who attained HBeAg sero-conversion were advised to discontinue Lamivudine after 6 months and followed up every 3 months thereafter, to see for relapse. Treatment was given for maximum of 3 years if not sero-converted. RESULTS: The annual incremental loss of HBeAg in patients receiving Lamivudine was 25 (41.6%) at end of 1st year, 33 (55%) at 2nd year and 35 (58.3%) at 3rd year. The corresponding rates for full sero-conversion were 17/60 (28.6%), 22/60 (36.6%) and 24/60 (40%) in the 3 years. HBeAg loss correlated with increased pre-therapy ALT levels (p = 0.002) and decreased pretreatment HBV-DNA levels (p = 0.004). The presence of cirrhosis had no influence on the rate of HBeAg loss. Relapse occurred in 35% (7/20) post-treatment at median time of 6 months. CONCLUSION: Indian patients showed a higher rate of HBeAg sero-conversion in the first year of Lamivudine treatment. This correlated with baseline ALT and inversely with HBV-DNA levels. Relapse rate after treatment was high and occurred soon after stopping treatment.

Adolescent↗
PubMed2005

Autoimmune hepatitis in India: profile of an uncommon disease.

BACKGROUND: Autoimmune hepatitis (AIH) has been reported to show considerable geographical variation in frequency and clinical manifestations. It is considered a rare cause of liver disease in India. The present study was undertaken to determine the incidence, clinical, biochemical and histological profile of AIH in this part of the world. METHODS: Patients presenting with acute or chronic liver disease between January 1999 and June 2002 were evaluated prospectively. AIH was diagnosed using the international autoimmune hepatitis group criteria. Workup included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA) using indirect immunofluorescence and liver biopsy if possible. RESULTS: Forty-one of 2401 (1.70%) patients were diagnosed to have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune hepatitis was 36.2 (15.9) years, 34 (89.4%) were females, and the duration of symptoms was 20.3 (20.5) months. Nineteen (50%) of them presented with chronic hepatitis, 13 (34.2%) as cirrhosis, 5 (13.1%) with acute hepatitis and 1 (2.6%) with cholestatic hepatitis. The presentations were jaundice in 21 (55.2%), pedal edema and hepatomegaly in 17 (44.7%), splenomegaly in 13 (34.2%), encephalopathy, abdominal pain in 9 (23.6%) and fever in 8 (21%). Twelve had esophageal varices and 3 had bled. Biochemical parameters were ALT 187 (360) U/L, AST 157 (193) U/L, ALP 246 (254) U/L, globulin 4.1 (1.6) g/dL, albumin 2.8 (0.9) g/dL, bilirubin 5.2 (7.4) mg/dL, prothrombin time 17 (7) sec and ESR 47 (17) sec. The autoimmune markers were SMA (24), ANA (15), both SMA and ANA (4), AMA (1), rheumatoid factor (2), pANCA (1), and Anti-LKM in none. Thirty (79%) patients had definite AIH and eight (21%) had probable AI hepatitis. Associated autoimmune diseases was seen in 15/38 (39.4%), diabetes 4, hypothyroidism 3, vitiligo 2, thrombocytopenia 2, rheumatoid arthritis 2, Sjogren's syndrome 1 and autoimmune polyglandular syndrome III in 1. Viral markers were positive in two patients, one presenting as acute hepatitis and HEV-IgM positive and another anti-HCV positive. CONCLUSION: In India, autoimmune hepatitis is uncommon and usually presents with chronic hepatitis or cirrhosis, acute hepatitis being less common. Age at presentation was earlier but clinical parameters and associated autoimmune diseases were similar to that reported from the west. Primary biliary cirrhosis is rare. Type II AIH was not observed.

Adolescent↗
PubMed2004

Molecular imaging of the transcription factor NF-kappaB, a primary regulator of stress response.

A wide range of environmental stress and human disorders involves inappropriate regulation of NF-kappaB, including cancers and numerous inflammatory conditions. We have developed transgenic mice that express luciferase under the control of NF-kappaB, enabling real-time non-invasive imaging of NF-kappaB activity in intact animals. We show that, in the absence of stimulation, strong, intrinsic luminescence is evident in lymph nodes in the neck region, thymus, and Peyer's patches. Treating mice with stressors, such as TNF-alpha, IL-1alpha, or lipopolysaccharide (LPS) increases the luminescence in a tissue-specific manner, with the strongest activity observable in the skin, lungs, spleen, Peyer's patches, and the wall of the small intestine. Liver, kidney, heart, muscle, and adipose tissue exhibit less intense activities. Exposure of the skin to a low dose of UV-B radiation increases luminescence in the exposed areas. In ocular experiments, LPS- and TNF-alpha injected NF-kappaB-luciferase transgenic mice exhibit a 20-40-fold increase in lens NF-kappaB activity, similar to other LPS- and TNF-alpha-responsive organs. Peak NF-kappaB activity occurs 6h after injection of TNF-alpha and 12h after injection of LPS. Peak activities occur, respectively, 3 and 6h later than that in other tissues. Mice exposed to 360J/m(2) of UV-B exhibit a 16-fold increase in NF-kappaB activity 6h after exposure, characteristically similar to TNF-alpha-exposed mice. Thus, in NF-kappaB-luciferase transgenic mice, NF-kappaB activity also occurs in lens epithelial tissue and is activated when the intact mouse is exposed to classical stressors. Furthermore, as revealed by real-time non-invasive imaging, induction of chronic inflammation resembling rheumatoid arthritis produces strong NF-kappaB activity in the affected joints. Finally, we have used the model to demonstrate NF-kappaB regulation by manipulating the Vitamin A status in mice. NF-kappaB activity is elevated in mice fed a Vitamin A deficient (VAD) diet, and suppressed by surplus doses of retinoic acid (RA). We thus demonstrate the development and use of a versatile model for monitoring NF-kappaB activation both in tissue homogenates and in intact animals after the use of classical activators, during disease progression and after dietary intervention.

Animals↗
PubMed2004

Vitamin A status significantly alters nuclear factor-kappaB activity assessed by in vivo imaging.

Our study aimed to investigate, in vivo, the relationship between vitamin A status and NF-kappaB activity, a transcription factor central in regulating inflammatory and immune responses. We used a novel transgenic murine NF-kappaB-luciferase reporter model that enabled molecular imaging of NF-kappaB activity in live mice via an intensified image-capture apparatus. Whole-body luminescence, which reflects overall NF-kappaB activity, was elevated 2.2-fold in vitamin A-deficient (VAD) mice compared with control mice. Specifically, NF-kappaB activity in VAD mice was increased 1.8-fold in the lymph nodes and 1.4-fold in the thymus and, NF-kappaB induction in UVB radiation-exposed skin was also enhanced in VAD mice compared with control mice. The administration of all-trans retinoic acid to VAD mice resulted in a transient reduction in NF-kappaB activity and, conversely, a single dose of the RAR-pan-antagonist, AGN 194310, administered to control mice, led to a marked, transient induction of whole-body luminescence. Our results suggest that vitamin A status, and vitamin A itself, affects NF-kappaB activity in vivo and that the elevated NF-kappaB activity in VAD may be a mechanism underlying some of the features of VAD syndrome.

Animals↗
PubMed2004

An unusual case of scalp laxity following weight reduction.

The advent of fast foods, increased mechanization,advanced telecommunication and improved living standards have caused human beings to adopt sedentary life styles leading to lesser means of expending calories, accumulation of body fat and tendency to be obese. Plastic surgery can be of great help in supporting patients in their attempts at weight reduction by removing resistant body fat and excising redundant skin that may not succumb to other means of weight reduction. The authors present an unusual case of a young gentleman who developed a rare laxity of the scalp following a drastic weight reduction. Scalp reduction led to a significant cosmetic improvement and psychological acceptance of body image. A review of literature and discussion on the management of this unusual case follows.

Adult↗
PubMed2003

Capillary high-performance liquid chromatographic determination of lutein and zeaxanthin in aqueous humor from a single mouse eye.

To protect the eye from ultraviolet phototoxicity caused by free radicals, ocular components such as the aqueous humor accumulate antioxidants, such as the carotenoids. Lutein and zeaxanthin are the only carotenoids known to be present in the aqueous humor. Due to the small sample volume, pooling of samples from an undesirable large number of animals is often required for sufficient sensitivity and statistically significant differences to be achieved. In this paper we present a rapid, sensitive and robust packed capillary high-performance liquid chromatographic visible detection method for the quantification of lutein and zeaxanthin in the aqueous humor of single mouse eyes.

Animals↗
PubMed2003

Teratogenicity of valproate conjugates with anticonvulsant activity in mice.

Valproic acid (VPA) is an effective antiepileptic medication, the use of which in females of childbearing age is complicated by its ability to induce birth defects, including neural tube defects (NTDs), in exposed embryos. In experimental settings, VPA reproducibly induces NTDs in laboratory animals such as the highly inbred SWV/Fnn mice. In search of new, efficacious derivatives of VPA that lack toxicity, the conjugates of VPA with amantadine (VPA-AMA) and N-3-aminopropyl-2-pyrrolidinone (VPA-PYR) have been synthesized and evaluated for their anticonvulsant activity. In the present study, the authors evaluated the teratogenicity potential of VPA-AMA and VPA-PYR using a well-established mouse model for antiepileptic drug teratogenicity. All tested compounds were injected intraperitoneally to pregnant dams on gestational day 8.5, and the fetuses examined on day 18.5. At the highest dose tested (3.61 mmol/kg), VPA-PYR was maternally lethal, whereas VPA-AMA induced excessive embryonic lethality. At a dose of 2.20 mmol/kg, VPA-PYR was not teratogenic to the exposed embryos; VPA-AMA induced NTDs in 8.2% of embryos, VPA caused 5.5% NTDs. 0.80 mmol/kg amantadine induced NTDs in 2.2% of the exposed fetuses. In conclusion, VPA-AMA has a comparable teratogenicity as does VPA, and it is proposed that the teratogenicity of VPA-AMA is due to the parent compound. Additional studies are needed to fully define and understand the structure-teratogenicity relationships of VPA analogues.

Abnormalities, Drug-Induced↗
PubMed2003

Strong in vivo activation of NF-kappaB in mouse lenses by classic stressors.

PURPOSE: To examine the in vivo activation of nuclear factor (NF)-kappaB in mouse lens epithelia by using bacterial lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, and UV-B radiation. METHODS: Transgenic mice containing the NF-kappaB-luciferase reporter were injected with LPS, TNF-alpha or, exposed to UV-B. After various exposure times, the mice were killed, and ocular, liver, lung, kidney, spleen, and skin tissue were obtained. Tissue homogenates were examined for luciferase activity with a luminometer. Groups of mice were also imaged in vivo through a light-intensified camera system to assess NF-kappaB activity. RESULTS: LPS- and TNF-alpha injected NF-kappaB-luciferase transgenic mice yielded 20- to 40-fold increases in lens NF-kappaB activity, similar to other LPS- and TNF-alpha-responsive organs. Peak NF-kappaB activity occurred 6 hours after injection of TNF-alpha and 12 hours after injection of LPS. Peak activities were, respectively, 3 and 6 hours later than that in other tissues. Mice exposed to 360 J/m(2) of UV-B exhibited a 16-fold increase in NF-kappaB activity 6 hours after exposure, which are characteristics similar to TNF-alpha-exposed mice. In vivo imaging of transgenic mice exposed to LPS, TNF-alpha, and UV-B radiation demonstrated a similarity between in vitro and in vivo measurements of NF-kappaB activity. CONCLUSIONS: In NF-kappaB-luciferase transgenic mice, NF-kappaB activity occurs in lens epithelial tissue and is activated when the intact mouse is exposed to bacterial LPS, TNF-alpha, or UV-B. Lens epithelial NF-kappaB kinetics were comparable to those of other tissues, indicating that NF-kappaB may play a role in progression or arrest of lens disorders.

Animals↗