DPD epitope-specific glutamic acid decarboxylase (GAD)65 autoantibodies in children with Type 1 diabetes.

AIM: To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. METHODS: We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody-positive samples were analysed for epitope specificities using recombinant Fab against the DPD-defined epitope of glutamate decarboxylase 65. RESULTS: After adjustment for age, positive DPD epitope recognition was significantly associated with higher C-peptide levels at onset (P = 0.02, r2 =0.21, n = 35), and high DPD recognition in the highest quartile tended to be associated with HbA1c ≤ 53 mmol/mol (7%) at the last follow-up [mean (sd) follow-up 1.3 (0.4) years; P = 0.07; for the model, P = 0.044, n = 30)]. Age- and sex-adjusted BMI percentile was significantly correlated with recognition of the DPD-defined epitope (P < 0.03, r2 =0.14, n = 34), but this correlation was driven by the older age group (age ≥ 10 years; P = 0.016, r2 =0.27, n = 21) and was not significant in younger children (P = 0.93, n = 13). There were no independent associations with sex, race/ethnicity, diabetic ketoacidosis, HbA1c , HLA DR3-DQ2/DR4-DQ8 or autoantibody number. CONCLUSIONS: Our findings suggest that recognition of the DPD-defined glutamate decarboxylase 65 autoantibody epitope at Type 1 diabetes onset is directly associated with ß-cell function, BMI and age, which supports the hypothesis that immunological factors contribute to the clinical heterogeneity of Type 1 diabetes. Larger studies relating epitope-specific glutamate decarboxylase 65 autoantibody to clinical phenotype in children with Type 1 diabetes are warranted.

Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes.

BACKGROUND/OBJECTIVE: Obesity increases the risk of cardiovascular disease and diabetic complications in type 1 diabetes. Adipokines, which regulate obesity-induced inflammation, may contribute to this association. We compared serum adipokines and inflammatory cytokines in obese and lean children with new-onset autoimmune type 1 diabetes. SUBJECTS AND METHODS: We prospectively studied 32 lean and 18 obese children (age range: 2-18 yr) with new-onset autoimmune type 1 diabetes and followed them for up to 2 yr. Serum adipokines [leptin, total and high molecular weight (HMW) adiponectin, omentin, resistin, chemerin, visfatin], cytokines [interferon (IFN)-gamma, interleukin (IL)-10, IL-12, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha] and C-reactive protein (CRP) were measured at a median of 7 wk after diagnosis (range: 3-16 wk). RESULTS: Lean children were 71.9% non-Hispanic White, 21.9% Hispanic, and 6.3% African-American, compared with 27.8, 55.6, and 16.7%, respectively, for obese children (p = 0.01). Compared with lean children, obese children had significantly higher serum leptin, visfatin, chemerin, TNF-alpha and CRP, and lower total adiponectin and omentin after adjustment for race/ethnicity and Tanner stage. African-American race was independently associated with higher leptin among youth ≥10 yr (p = 0.007). Leptin levels at onset positively correlated with hemoglobin A1c after 1-2 yr (p = 0.0001) independently of body mass index, race/ethnicity, and diabetes duration. Higher TNF-alpha was associated with obesity and female gender, after adjustment for race/ethnicity (p = 0.0003). CONCLUSION: Obese children with new-onset autoimmune type 1 diabetes have a proinflammatory profile of circulating adipokines and cytokines that may contribute to the development of cardiovascular disease and diabetic complications.

Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats.

This study investigated the oxidative stress induced after acute oral treatment with 500, 1000 and 2000 mg kg⁻¹ doses of Al2O3 -30 and -40 nm and bulk Al2O3 in Wistar rats. Both the nanomaterials induced significant oxidative stress in a dose-dependent manner in comparison to the bulk. There was no significant difference between the two nanomaterials. However, the effect decreased with increase with time after treatment. The histopathological examination showed lesions only in liver with Al2O3 nanomaterials at 2000 mg kg⁻¹.

Effect of a lifestyle intervention on change in cardiorespiratory fitness in adults with type 2 diabetes: results from the Look AHEAD Study.

OBJECTIVE: To examine the effect of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in fitness and physical activity in the Look AHEAD trial. DESIGN: Randomized clinical trial to compare a lifestyle intervention for weight loss with a DSE condition in individuals with type 2 diabetes. SUBJECTS: Data from 4376 overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and had available fitness data were analyzed. INTERVENTION: Subjects were randomly assigned to DSE or ILI. DSE received standard care plus three education sessions over the 1-year period. ILI included individual and group contact throughout the year, restriction in energy intake and 175 min per week of prescribed physical activity. MEASUREMENTS: Fitness was assessed using a submaximal graded exercise test. Physical activity was assessed by questionnaire in a subset of 2221 subjects. RESULTS: Change in fitness was statistically greater in ILI vs DSE after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate analysis showed that change in fitness was greater in overweight vs obese Class II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and physical activity (r=0.42) were significantly correlated with weight loss (P<0.0001). CONCLUSIONS: The ILI was effective in increasing physical activity and improving cardiorespiratory fitness in overweight and obese individuals with type 2 diabetes. This effect may add to weight loss in improving metabolic control in patients in lifestyle intervention programs.

In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test.

Advances in nanotechnology and its usage in various fields have led to the exposure of humans to engineered nanomaterials (NMs) and there is a need to tackle the potential human health effects before these materials are fully exploited. The main purpose of the current study was to assess whether aluminium oxide NMs (Al(2)O(3)-30 nm and Al(2)O(3)-40 nm) could cause potential genotoxic effects in vivo. Characterization of Al(2)O(3)-30 nm and Al(2)O(3)-40 nm was done with transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry prior to their use in this study. The genotoxicity end points considered in this study were the frequency of micronuclei (MN) and the percentage of tail DNA (% Tail DNA) migration in rat peripheral blood cells using the micronucleus test (MNT) and the comet assay, respectively. Genotoxic effects were evaluated in groups of female Wistar rats (five per group) after single doses of 500, 1000 and 2000 mg/kg body weight (bw) of Al(2)O(3)-30 nm, Al(2)O(3)-40 nm and Al(2)O(3)-bulk. Al(2)O(3)-30 nm and Al(2)O(3)-40 nm showed a statistically significant dose-related increase in % Tail DNA for Al(2)O(3)-30 nm and Al(2)O(3)-40 nm (P < 0.05). However, Al(2)O(3)-bulk did not induce statistically significant changes over control values. The MNT also revealed a statistically significant (P < 0.05) dose-dependent increase in the frequency of MN, whereas Al(2)O(3)-bulk did not show any significant increase in frequency of MN compared to control. Cyclophosphamide (40 mg/kg bw) used as a positive control showed statistically significant (P < 0.001) increase in % Tail DNA and frequency of MN. The biodistribution of Al(2)O(3)-30 nm and Al(2)O(3)-40 nm and Al(2)O(3)-bulk in different rat tissues, urine and feces was also studied 14 days after treatment using inductively coupled plasma mass spectrometry. The data indicated that tissue distribution of Al(2)O(3) was size dependent. Our findings suggest that Al(2)O(3) NMs were able to cause size- and dose-dependent genotoxicity in vivo compared to Al(2)O(3)-bulk and control groups.

Evaluation of genotoxic effects of oral exposure to aluminum oxide nanomaterials in rat bone marrow.

Nanomaterials have novel properties and functions because of their small size. The unique nature of nanomaterials may be associated with potentially toxic effects. The aim of this study was to evaluate the in vivo genotoxicity of rats exposed with Aluminum oxide nanomaterials. Hence in the present study, the genotoxicity of Aluminum oxide nanomaterials (30 and 40 nm) and its bulk material was studied in bone marrow of female Wistar rats using chromosomal aberration and micronucleus assays. The rats were administered orally with the doses of 500, 1000 and 2000 mg/kg bw. Statistically significant genotoxicity was observed with Aluminum oxide 30 and 40 nm with micronucleus as well as chromosomal aberration assays. Significantly (p < 0.05 or p < 0.001) increased frequency of MN was observed with 1000 and 2000 mg/kg bw dose levels of Aluminum oxide 30 nm (9.4 +/- 1.87 and 15.2 +/- 2.3, respectively) and Aluminum oxide 40 nm (8.1 +/- 1.8 and 13.9 +/- 2.21, respectively) over control (2.5 +/- 0.7) at 30 h. Likewise, at 48 h sampling time a significant (p < 0.05 or p < 0.001) increase in frequency of MN was evident at 1000 and 2000 mg/kg bw dose levels of Aluminum oxide 30 nm (10.6 +/- 1.68 and 16.6 +/- 2.66, respectively) and Aluminum oxide 40 nm (9.0 +/- 1.38 and 14.7 +/- 1.68, respectively) compared to control (1.8 +/- 0.75). Significantly increased frequencies (p < 0.05 or p < 0.001) of chromosomal aberrations were observed with Aluminum oxide 30 nm (1000 and 2000 mg/kg bw) and Aluminum oxide 40 nm (2000 mg/kg bw) in comparison to control at 18 and 24 h. Further, since there is need for information on the toxicokinetics of nanomaterials, determination of these properties of the nanomaterials was carried out in different tissues, urine and feces using inductively coupled plasma mass spectrometry (ICP-MS). A significant size dependent accumulation of Aluminum oxide nanomaterials occurred in different tissues, urine and feces of rats as shown by ICP-MS data. The results of our study suggest that exposure to Aluminum oxide nanomaterials has the potential to cause genetic damage.

Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini.

Two classes of human cDNA encoding the insulin/mitogen-activated p70 S6 kinase have been isolated; the two classes differ only in the 5' region, such that the longer polypeptide (p70 S6 kinase alpha I; calculated Mr 58,946) consists of 525 amino acids, of which the last 502 residues are identical in sequence to the entire polypeptides encoded by the second cDNA (p70 S6 kinase alpha II; calculated Mr 56,153). Both p70 S6 kinase polypeptides predicted by these cDNAs are present in p70 S6 kinase purified from rat liver, and each is thus expressed in vivo. Moreover, both polypeptides are expressed from a single mRNA transcribed from the (longer) p70 S6 kinase alpha I cDNA through the utilization of different translational start sites. Although the two p70 S6 kinase polypeptides differ by only 23 amino acid residues, the slightly longer alpha I polypeptide exhibits anomalously slow mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), migrating at an apparent Mr of 90,000 probably because of the presence of six consecutive Arg residues immediately following the initiator methionine. Transient expression of p70 alpha I and alpha II S6 kinase cDNA in COS cells results in a 2.5- to 4-fold increase in overall S6 kinase activity. Upon immunoblotting, the recombinant p70 polypeptides appear as a closely spaced ladder of four to five bands between 65 and 70 kDa (alpha II) and 85 and 90 kDa (alpha I). Transfection with the alpha II cDNA yields only the smaller set of bands, while transfection with the alpha I cDNA generates both sets of bands. Mutation of Met-24 in the alpha I cDNA to Leu or Thr suppresses synthesis of the alpha II polypeptides. Only the p70 alpha I and alpha II polypeptides of slowest mobility on SDS-PAGE comigrate with the 70- and 90-kDa proteins observed in purified rat liver S6 kinase. Moreover, it is the recombinant p70 polypeptides of slowest mobility that coelute with S6 kinase activity on anion-exchange chromatography. The slower mobility and higher enzymatic activity of these p70 proteins is due to Ser/Thr phosphorylation, inasmuch as treatment with phosphatase 2A inactivates kinase activity and increases the mobility of the bands on SDS-PAGE in an okadaic acid-sensitive manner. Thus, the recombinant p70 S6 kinase undergoes multiple phosphorylation and partial activation in COS cells. Acquisition of S6 protein kinase catalytic function, however, is apparently restricted to the most extensively phosphorylated recombinant polypeptides.

New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetes and the effect of ethnicity.

BACKGROUND: Diabetic ketoacidosis (DKA) has been reported to occur in type 2 diabetes, but the frequency and distinguishing features of this syndrome remain to be defined. We determined the "diabetic types," ethnic distributions, and phenotypes of patients with DKA in an urban hospital. METHODS: We reviewed the hospital admissions and followed the clinical course of adults who developed DKA. We classified patients as "type 1," "type 2," or "new onset" based on their treatment history. New-onset patients were reassessed 2 1/2 years or more after the episode of DKA and classified as "type 1" or "type 2" based on insulin requirements. We compared the groups for ethnic distributions and clinical features. RESULTS: Of 141 patients, 55 (39%) who presented with DKA had type 2 diabetes, while 75 (53%) had type 1 diabetes and 11 (8%) could not be "typed." Hispanics mainly had type 2 and whites predominantly had type 1, while African Americans had a slight preponderance of type 1 diabetes (P=.001). Type 1 patients were mainly lean, while the body mass indexes (BMIs) (calculated as the weight in kilograms divided by the square of height in meters) of type 2 patients were bimodally distributed (33% with BMI<25 and 51% with BMI>30; P<.001). Age of onset of diabetes was predominantly younger than 40 years in the type 1 group but was more broadly distributed in the type 2 group (P<.001). Ninety-three percent of the new-onset patients who were reassessed had type 2 diabetes. Half of the type 2 patients had no identifiable stress factor associated with the episode of DKA. CONCLUSIONS: A high proportion of DKA in nonwhite adults occurs in persons with type 2 diabetes, especially in those with previously undiagnosed diabetes. The frequency and clinical heterogeneity of this syndrome in a multiethnic population have significant implications for the diagnosis, classification, and management of adults with diabetes.

Glucocorticoid-induced ketoacidosis in gestational diabetes: sequela of the acute treatment of preterm labor. A case report.

Pregnancy induces complex changes in energy metabolism, manifested clinically by insulin resistance, low fasting blood glucose levels, and proneness to ketosis. It is quite unusual for pregnant women who do not have type I diabetes to progress from ketosis to frank ketoacidosis, although this phenomenon is common in larger mammals. In the case described here, glucocorticoid administration in the setting of a prolonged fast triggered a metabolic cascade leading to ketoacidosis in a pregnant woman without type 1 diabetes. Other details of this illustrative case serve to synthesize several disparate observations regarding the pathogenesis of pregnancy ketoacidosis. Physicians should be aware of the potential for rapidly developing ketoacidosis with atypical biochemical and clinical features in pregnant women who are treated with high doses of glucocorticoids.

Viral mechanisms of adipose dysfunction: lessons from HIV-1 Vpr.

HIV-associated lipodystrophy is a heterogeneous, evolving condition associated with fundamental defects in adipose tissue differentiation, turnover and function. Although many antiretroviral drugs can affect adipose tissues adversely, clinical evidence suggests that factors associated with the virus per se could play a role. We have focused on the possibility that an HIV accessory protein, viral protein R (Vpr) could dysregulate metabolically critical transcription factors to cause the adipose dysfunction. In a recent study published in Science Translational Medicine, we utilized 2 animal models to show that Vpr, produced in tissues that sequester HIV after antiretroviral therapy, can act in a paracrine or endocrine fashion to disrupt adipocyte differentiation and function by inhibiting PPARγ target gene expression and activating glucocorticoid target gene expression. The phenotypic consequences included many features typical of the human syndrome, including accelerated lipolysis, increased macrophage infiltration in adipose tissue, diminished size of white adipose depots and hepatic steatosis. In this commentary, we summarize the background, results, and implications of these studies, and raise important questions for future investigation. More broadly, these studies suggest that chronic viral infections may be a causative factor in the pathogenesis of some forms of lipid metabolic disease, insulin resistance, and diabetes.

Abnormal guanine nucleotide regulatory protein in MVP dysautonomia: evidence from reconstitution of Gs.

We and others have used the term MVP dysautonomia for a particular subset of hyperadrenergic dysautonomia patients. The role of the stimulatory guanine nucleotide regulatory protein (Gs) in this dysautonomia was studied by cholate extraction of Gs from erythrocytes from 11 normal subjects and 14 symptomatic dysautonomic patients and reconstitution into cyc-S49 lymphoma membranes, which have normal receptor and adenylyl cyclase but lack Gs. Isoproterenol-stimulated adenylyl cyclase activity in the dysautonomia group was increased compared to that in controls [3.66 +/- 0.20 (mean +/- SE; n = 14) vs. 2.87 +/- 0.14 (n = 11) U cyc- reconstituted activity/mg erythrocyte protein; P less than 0.05]. beta-Adrenergic receptor high affinity state formation was greatest in the severely symptomatic group [KL/KH: severe symptoms, 130 +/- 48 (n = 6); mild symptoms, 33 +/- 7 (n = 7); control, 27 +/- 6 (n = 11); severe dysautonomia distinct, P less than 0.017]. Sodium dodecyl sulfate-polyacrylamide gels of cholera toxin-dependent ADP-ribosylated G-proteins yielded no gross distinction between severely symptomatic and control groups. This subset of hyperadrenergic dysautonomia patients, thus, has supercoupled beta 2-adrenergic receptors (increase in both agonist binding and cyclase activation) conferred by an abnormal Gs, whose effects on agonist binding reflect the severity of illness.

Developmental changes in expression of myotonic dystrophy protein kinase in the rat central nervous system.

Myotonic dystrophy protein kinase (DMPK) is the protein product of the genetic locus associated with myotonic dystrophy, in which alterations of muscle excitability, cardiac conduction defects, mental retardation, and cognitive deficiencies are inherited as an autosomal dominant trait. DMPK belongs to a novel protein serine/threonine kinase family, but its regulation and physiological functions have not been specified. In a first step toward understanding the functions of DMPK in the central nervous system, we have characterized its localization and developmental pattern of expression in rat brain and spinal cord by using a monospecific rabbit antiserum produced against bacterially expressed DMPK. Expression of DMPK begins after birth and increases gradually to peak at postnatal day 21 with antibody labeling of neuronal cell types in many regions. After postnatal day 21 and proceeding to the adult, the pattern of expression becomes more restricted, with localization to certain regions or cell groups in the central nervous system. Electron microscopy reveals localization within adult spinal motor neurons to the endoplasmic reticulum and dendritic microtubules. The adult localizations suggest that DMPK may function in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control.

Malignant lymphoma of the heart in acquired immune deficiency syndrome.

Malignant lymphoma of the heart was found at autopsy of two homosexual men with acquired immune deficiency syndrome (AIDS). Both patients had symptoms and signs of cardiac dysfunction, and it is likely that the immediate cause of their deaths was related to the cardiac tumors. In both cases, there was lymphomatous involvement of other organs, but the heart was the predominant site of disease. There was prominent endocardial and myocardial involvement, and both tumors were high grade large cell lymphomas with plasmacytoid features. In both instances, the lymphomas were diagnosed only at the autopsy, despite extensive antemortem cardiac evaluation in one patient. The clinicopathologic correlation, gross pathologic and histologic findings of the tumor, and their pattern and distribution suggest a de novo origin of the lymphoma in the heart in these two patients. Lymphomatous infiltration of the heart should be suspected in patients with AIDS who have cardiac symptoms.

Rectal administration of iodide and propylthiouracil in the treatment of thyroid storm.

We administered potassium iodide and propylthiouracil per rectum, in conjunction with intravenous dexamethasone and propranolol, for emergent treatment of a patient in thyroid storm with small bowel obstruction. Shortly after initiation of this treatment, the patient successfully underwent two emergent surgical procedures for resection of an intestinal volvulus with advanced peritonitis. Serum levels of iodide and propylthiouracil showed substantial absorption of these drugs via the rectal route. Measurement of 24-h urinary-free iodide indicated that the bioavailability of potassium iodide delivered by retention enema was at least 40%. Parenteral iodide preparations have been unavailable in the past, and continue to be difficult to obtain emergently. Rectal administration of inorganic iodide is an effective, readily available and less expensive alternative to parenteral sodium iodide for patients in thyroid storm with upper gastrointestinal tract dysfunction.

Abnormal Gs function in mitral valve prolapse dysautonomia is not associated with abnormal alpha S cDNA sequence.

We have previously shown that a subset of patients with mitral valve prolapse and hyperadrenergic symptoms has enhanced isoprenaline-stimulated beta-adrenergic receptor high-affinity state formation (supercoupling) and increased adenylyl cyclase activity due to abnormal signal transduction by the stimulatory guanine nucleotide regulatory protein (Gs). In this study we looked for an alteration of the nucleotide coding sequence of the gene for alpha s, the subunit of Gs that is directly responsible for formation of the high affinity state and adenylyl cyclase activation, by cloning and sequencing the alpha s cDNA from neutrophils of 4 symptomatic patients and 1 control. No difference was observed between patients and control in the alpha s cDNA sequence. The splice variant concentrations in the fully expressed protein were also grossly unchanged in five patients and four controls. These data show that a primary alteration of the alpha s gene coding sequence is not responsible for defective Gs-associated signal transduction in dysautonomic MVP patients, and suggest that the molecular lesion could be an abnormal posttranslational modification of alpha s, a defect in the beta or gamma subunits of Gs, or an unusual interaction between the subunits in the Gs of these patients.

Monitoring of oxidative stress in nurses occupationally exposed to antineoplastic drugs.

Antineoplastic drugs (ANDs) have been in clinical usage for more than five decades. The nonselective mechanism of action of ANDs between cancerous and noncancerous cells had well documented side effects such as acute symptoms, reproductive health issues, and potential cancer development in healthcare workers as a result of occupational exposure. The anticancer mechanism of ANDs is the generation of reactive oxygen species (ROS) which are responsible for various side effects in patients undergoing chemotherapy and the healthcare personnel occupationally exposed to them. ROS have potential to damage lipids, DNA, proteins, and so on leading to oxidative stress condition. The aim of this study was to evaluate the possible oxidative stress effect of antineoplastic drugs in nurses who routinely handle ANDs in an oncology hospital in south India. Malondialdehyde levels, reduced glutathione content, and glutathione S-transferase activity were analyzed in serum collected from 60 female nurses handling ANDs and compared with equal number of healthy volunteers matched by age and sex except AND exposure. The results showed statistically significant (P < 0.05) increase in malondialdehyde levels in the serum of exposed nurses. However, glutathione content and glutathione S-transferase activity was significantly decreased in these nurses. Our study suggests that the nurses occupationally exposed to ANDs were susceptible to the oxidative stress and emphasizes the need for a harmonized safe handling approach that assures minimal risk to the working nurses.

Intramuscular haemangioma of mylohyoid muscle: A case report.

OBJECTIVE: To report a case of intramuscular haemangioma (IMH) with a rare presentation in the mylohyoid, with emphasis on the clinical appearance, and histologic characteristics of the lesion. METHOD: Case report and review of the literature. CONCLUSION: Neck swellings can often present a diagnostic dilemma, with a wide preoperative differential diagnosis. IMH are rare benign haemangiomas occurring within the skeletal muscle. They account for approximately 1% of all haemangiomas. These are uncommon in the head and neck region and occur most frequently in the trunk and extremities. In the head and neck, masseter and trapezius are the most common sites involved. Intramuscular haemangioma is seldom diagnosed preoperatively, perhaps due to unfamiliarity with this uncommon lesion and nonspecific clinical findings.

In vitro mutagenicity assessment of aluminium oxide nanomaterials using the Salmonella/microsome assay.

The aim of the current study was to evaluate the potential mutagenicity of aluminium oxide nanomaterials (NMs) (Al(2)O(3)-30 nm and Al(2)O(3)-40 nm). Characterization of the NMs was done before the initiation of the study. The mutagenicity of the NMs was studied by the Ames test with Salmonella typhimurium TA100, TA1535, TA98, TA97a and TA102 strains, in the presence and absence of the S9 mixture. Based on a preliminary cytotoxicity study conducted on the strains, different concentrations of Al(2)O(3)-30 nm, Al(2)O(3)-40 nm and Al(2)O(3)-bulk were selected. At all the concentrations tested, Al(2)O(3)-30 nm and Al(2)O(3)-40 nm did not significantly increase the number of revertant colonies compared to the Al(2)O(3)-bulk and control with or without S9 mixture. Our findings suggest that Al(2)O(3) NMs were devoid of any size and concentration dependent mutagenicity compared to the Al(2)O(3)-bulk and control.

Isolated sphenoid sinus disease - a retrospective analysis.

OBJECTIVE: To evaluate the etiology, symptoms, signs, imaging, surgical findings and outcomes of isolated sphenoid sinus disease (ISSD). DESIGN: Retrospective study. SETTINGS: Tertiary university based referral center. MATERIALS AND METHODS: All 8 patients aged 17-63, managed surgically in the department of ENT and Head and Neck Surgery at St. John's Medical College and Hospital, Bangalore from 2006 to 2008 for ISSD. Demographic data, presenting signs and symptoms endoscopic and imaging findings, surgical management, surgical pathology and clinical outcomes were investigated in the above patients. RESULTS: Of the 8 cases of ISSD, 5 were male; 3 were female, with an age range of 17-63 years. The most common presenting symptom was headache (7 patients [87.5%]), followed by nasal obstruction and recurrent URTI (5 cases [62.5%]). Imaging included CT and/or MRI studies in all cases. Sphenoid sinus pathology was varied and included 5 (62.5%) inflammatory cases, 1 (11.1%) cerebrospinal fluid fistula and 2 (22.2%) cases of sphenoid sinus neop;asms. Of the inflammatory cases 2 (40%) had isolated polyps in the sphenoid sinus [sphenochoanal polyps] and 3 (60%) had fungal sinusitis. Treatment was surgical, endoscopic transnasal sphenoidotomy under general anesthesia in all 5 patients with inflammatory ISSD Two patients with sphenoid sinus tumors underwent endoscopic biopsy. CONCLUSION: ISSD is rare. A high index of suspicion is required for diagnosis, which should be an active process and not one of exclusion. Both diagnostic nasal endoscopy and CT imaging are essential for diagnosis. The direct approach to the sphenoid sinus, transnasal endoscopic sphenoidotomy without ethmoidectomy is safe and effective. With early and adequate surgery we were able to avoid the morbidity associated with ISSD.