Carbohydrate sources deferentially influence growth performances, microbial dynamics and immunomodulation in Pacific white shrimp (Litopenaeus vannamei) under biofloc system.

This study aims to evaluate the influence of different carbohydrate sources on water quality, growth performance and immunomodulation in pacific white shrimp and to find an alternate for molasses in biofloc system. The experiment consists of 8 biofloc treatments with different carbon sources, C1 (maida flour), C2 (wheat flour), C3 (gram flour), C4 (millet flour), C5 (rice flour), C6 (corn flour), C7 (molasses), C8 (multigrain flour) and un-supplemented control C0 was conducted in 200 L tank system for 120 days. Shrimp juveniles of average weight 1 g were stocked at the rate of 300 nos/m3. Shrimp reared in C8, C7 and C4 treatments had similar growth, survival rate, and disease resistance and were significantly higher (P < 0.05) than other treatments including control. Immune parameters like total hemocyte count (THC) and prophenoloxidase (ProPO) activity showed significantly higher (P < 0.05) levels in biofloc treatment groups. The genes targeting the proPO cascade (PX, BGBP) and antioxidant defense systems (SOD, MnSOD, CAT) revealed significant upregulation in the transcript levels indicating an enhancement in the immune-regulatory functions in the BFT groups. The results suggest that millets and multigrain flour can effectively replace molasses as the carbohydrate source for biofloc system and the biofloc system offers higher growth, survival, and immunomodulation than control.

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging.

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat.

Anti-thyroid peroxidase antibody in vitiligo: a prevalence study.

Aim. The aim of the study was to study the relation of vitiligo with demographic data like age, sex, and duration and determine the prevalence of thyroid autoimmunity in vitiligo patients. Materials and Methods. This study was a cross sectional study consisting of 100 patients clinically diagnosed (old and new) as having vitiligo irrespective of age or sex. Patients with known thyroid disease on supplementation therapy, or who had undergone thyroid surgery, those on antithyroid medication, patients with other causes of leukoderma, and cases who do not provide informed consent were excluded from the study. Serum TSH and anti-TPO antibodies were measured in all the patients. Results. The prevalence of anti-TPO antibody positivity was found to be 28%. Conclusion. According to our study, none of our vitiligo patients had symptoms or signs of thyroid disease at the time of presentation but, on biochemical evaluation, anti-TPO antibodies were found in a considerable number of patients. Hence, we recommend screening of these patients with thyroid antibodies.

BI-69A11 enhances susceptibility of colon cancer cells to mda-7/IL-24-induced growth inhibition by targeting Akt.

BACKGROUND: Akt and its downstream signalling pathways contribute to the aetiology and progression of colorectal carcinoma (CRC). Targeting the Akt pathway is an attractive strategy but few chemotherapeutic drugs have been used to treat CRC with only limited success. BI-69A11, a small molecule inhibitor of Akt, efficiently inhibits growth in melanoma cells. Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 promotes cancer-selective apoptosis when delivered by a tropism-modified replication incompetent adenovirus (Ad.5/3-mda-7). However, Ad.5/3-mda-7 displays diminished antitumour efficacy in several CRC cell lines, which correlates with the expression of K-RAS. METHODS: The individual and combinatorial effect of BI-69A11 and Ad.5/3-mda-7 in vitro was studied by cell viability, cell cycle, apoptosis and invasion assays in HT29 and HCT116 cells containing wild type or mutant K-ras, respectively. In vivo HT29 tumour xenografts were used to test the efficacy of the combination treatment. RESULTS: BI-69A11 inhibited growth and induced apoptosis in CRC. However, combinatorial treatment was more effective compared with single treatment. This combination showed profound antitumour and anti angiogenic effects in vitro and in vivo by downregulating Akt activity. CONCLUSIONS: BI-69A11 enhances the antitumour efficacy of Ad.5/3-mda-7 on CRC overexpressing K-RAS by inducing apoptosis and regulating Akt activity thereby warranting further evaluation in treating CRC.

A mechanistic mathematical model for the catalytic action of glutathione peroxidase.

Glutathione peroxidase (GPx) is a well-known seleno-enzyme that protects cells from oxidative stress (e.g., lipid peroxidation and oxidation of other cellular proteins and macromolecules), by catalyzing the reduction of harmful peroxides (e.g., hydrogen peroxide: H2O2) with reduced glutathione (GSH). However, the catalytic mechanism of GPx kinetics is not well characterized in terms of a mathematical model. We developed here a mechanistic mathematical model of GPx kinetics by considering a unified catalytic scheme and estimated the unknown model parameters based on different experimental data from the literature on the kinetics of the enzyme. The model predictions are consistent with the consensus that GPx operates via a ping-pong mechanism. The unified catalytic scheme proposed here for GPx kinetics clarifies various anomalies, such as what are the individual steps in the catalytic scheme by estimating their associated rate constant values and a plausible rationale for the contradicting experimental results. The developed model presents a unique opportunity to understand the effects of pH and product GSSG on the GPx activity under both physiological and pathophysiological conditions. Although model parameters related to the product GSSG were not identifiable due to lack of product-inhibition data, the preliminary model simulations with the assumed range of parameters show that the inhibition by the product GSSG is negligible, consistent with what is known in the literature. In addition, the model is able to simulate the bi-modal behavior of the GPx activity with respect to pH with the pH-range for maximal GPx activity decreasing significantly as the GSH levels decrease and H2O2 levels increase (characteristics of oxidative stress). The model provides a key component for an integrated model of H2O2 balance under normal and oxidative stress conditions.

Chemoprevention gene therapy (CGT): novel combinatorial approach for preventing and treating pancreatic cancer.

Pancreatic cancer remains one of the deadliest of all cancers despite aggressive surgical treatment combined with adjuvant radiotherapy and chemotherapy. Chemoresistance and radioresistance are the principal causes of failure of pancreatic cancer patients to respond to therapy. Conditionally replication competent adenovirus (CRCA)-based cancer gene therapy is an innovative strategy for treating cancers displaying inherent resistance to treatment. Limitations of current adenovirus (Ad)-based gene therapies for malignant tumors include lack of cancer-specificity, and effective and targeted delivery. To remedy this situation, CRCAs have been designed that express E1A, necessary for Ad replication, under the control of a cancer-specific progression elevated gene-3 promoter (PEG-Prom) with concomitant expression of an immunomodulatory cytokine, such as mda-7/IL-24 or interferon-γ (IFN-γ), under the control of a ubiquitous and strong cytomegalovirus promoter (CMV-Prom) from the E3 region. These bipartite CRCAs, when armed with a transgene, are called cancer terminator viruses (CTVs), i.e., Ad.PEG-E1A-CMV-mda-7 (CTV-M7) and Ad.PEG-E1A-CMV-IFN-γ (CTV-γ), because of their universal effectiveness in cancer treatment irrespective of p53/pRb/p16 or other genetic alterations in tumor cells. In addition to their selective oncolytic effects in tumor cells, the potent 'bystander antitumor' properties of MDA-7/IL-24 and IFN-γ embody the CTVs with expanded treatment properties for both primary and distant cancers. Pancreatic cancer cells display a "translational block" of mda-7/IL-24 mRNA, limiting production of MDA-7/IL-24 protein and cancer-specific apoptosis. Specific chemopreventive agents abrogate this "translational block" resulting in pancreatic cancer-specific killing. This novel chemoprevention gene therapy (CGT) strategy holds promise for both prevention and treatment of pancreatic cancers where all other strategies have proven ineffective.

Water desalination using capacitive deionization with microporous carbon electrodes.

Capacitive deionization (CDI) is a water desalination technology in which salt ions are removed from brackish water by flowing through a spacer channel with porous electrodes on each side. Upon applying a voltage difference between the two electrodes, cations move to and are accumulated in electrostatic double layers inside the negatively charged cathode and the anions are removed by the positively charged anode. One of the key parameters for commercial realization of CDI is the salt adsorption capacity of the electrodes. State-of-the-art electrode materials are based on porous activated carbon particles or carbon aerogels. Here we report the use for CDI of carbide-derived carbon (CDC), a porous material with well-defined and tunable pore sizes in the sub-nanometer range. When comparing electrodes made with CDC with electrodes based on activated carbon, we find a significantly higher salt adsorption capacity in the relevant cell voltage window of 1.2-1.4 V. The measured adsorption capacity for four materials tested negatively correlates with known metrics for pore structure of the carbon powders such as total pore volume and BET-area, but is positively correlated with the volume of pores of sizes <1 nm, suggesting the relevance of these sub-nanometer pores for ion adsorption. The charge efficiency, being the ratio of equilibrium salt adsorption over charge, does not depend much on the type of material, indicating that materials that have been identified for high charge storage capacity can also be highly suitable for CDI. This work shows the potential of materials with well-defined sub-nanometer pore sizes for energy-efficient water desalination.

IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR.

As an established mediator of inflammation, interleukin-6 (IL-6) is implicated to facilitate prostate cancer progression to androgen independence through transactivation of the androgen receptor. However, whether IL-6 has a causative role in de novo prostate tumorigenesis was never investigated. We now provide the first evidence that IL-6 can induce tumorigenic conversion and further progression to an invasive phenotype of non-tumorigenic benign prostate epithelial cells. Moreover, we find that paracrine IL-6 stimulates the autocrine IL-6 loop and autocrine activation of insulin-like type I growth factor receptor (IGF-IR) to confer the tumorigenic property and also that activation of signal transducer and activator of transcription 3 (STAT3) is critical in these processes. Inhibition of STAT3 activation or IGF-IR signaling suppresses IL-6-mediated malignant conversion and the associated invasive phenotype. Inhibition of STAT3 activation suppresses IL-6-induced upregulation of IGF-IR and its ligands, namely IGF-I and IGF-II. These findings indicate that IL-6 signaling cooperates with IGF-IR signaling in the prostate microenvironment to promote prostate tumorigenesis and progression to aggressiveness. Our findings suggest that STAT3 and IGF-IR may represent potential effective targets for prevention or treatment of prostate cancer.

Human polynucleotide phosphorylase (hPNPase(old-35)): an evolutionary conserved gene with an expanding repertoire of RNA degradation functions.

Human polynucleotide phosphorylase (hPNPase(old-35)) is an evolutionary conserved RNA-processing enzyme with expanding roles in regulating cellular physiology. hPNPase(old-35) was cloned using an innovative 'overlapping pathway screening' strategy designed to identify genes coordinately regulated during the processes of cellular differentiation and senescence. Although hPNPase(old-35) structurally and biochemically resembles PNPase of other species, overexpression and inhibition studies reveal that hPNPase(old-35) has evolved to serve more specialized and diversified functions in humans. Targeting specific mRNA or non-coding small microRNA, hPNPase(old-35) modulates gene expression that in turn has a pivotal role in regulating normal physiological and pathological processes. In these contexts, targeted overexpression of hPNPase(old-35) represents a novel strategy to selectively downregulate RNA expression and consequently intervene in a variety of pathophysiological conditions.

Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1.

Enhanced expression of the CCN family of secretory integrin-binding proteins correlates with many essential components of the cancerous state, including tumor cell adhesion, proliferation, invasion and migration. Consequently, CCN1 expression is elevated in various cancers, including breast cancer, and its expression directly correlates with poor patient prognosis. Using subtraction-hybridization, combined with induction of cancer cell terminal differentiation, we cloned SARI (suppressor of activator protein (AP)-1, regulated by interferon (IFN)), an IFN-beta-inducible, potent tumor suppressor gene that exerts cancer-selective growth inhibitory effects. Forced expression of SARI using an adenovirus (Ad.SARI) inhibits AP-1 function and downregulates CCN1 expression in multiple cancer lineages, resulting in a profound inhibition in anchorage-independent cell growth and tumor cell invasion. Overexpression of SARI reduces CCN1-promoter activity through inhibition of AP-1 binding. Accordingly, SARI selectively blocks expression of the transformed state in rat embryo fibroblast cells that stably overexpress c-Jun. These results illustrate that SARI inhibits AP-1 transactivating factor binding to the cis-element of the CCN1 promoter, possibly through its interaction with c-Jun. Overall, SARI can directly inhibit CCN1-induced transformation by inhibiting the transcription of CCN1, as well as indirectly by inhibiting the expression of c-Jun (and hence blocking AP-1 activity). In these contexts, transformed cells 'addicted' to AP-1 activity are rendered susceptible to SARI-mediated inhibition of expression of the transformed phenotype.

A database of thermodynamic quantities for the reactions of glycolysis and the tricarboxylic acid cycle.

Analysis of biochemical systems requires reliable and self-consistent databases of thermodynamic properties for biochemical reactions. Here a database of thermodynamic properties for the reactions of glycolysis and the tricarboxylic acid cycle is developed from measured equilibrium data. Species-level free energies of formation are estimated on the basis of comparing thermodynamic model predictions for reaction-level equilibrium constants to previously reported data obtained under different experimental conditions. Matching model predictions to the data involves applying state corrections for ionic strength, pH, and metal ion binding for each input experimental biochemical measurement. By archiving all of the raw data, documenting all model assumptions and calculations, and making the computer package and data available, this work provides a framework for extension and refinement by adding to the underlying raw experimental data in the database and/or refining the underlying model assumptions. Thus the resulting database is a refinement of preexisting databases of thermodynamics in terms of reliability, self-consistency, transparency, and extensibility.

Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells.

Gene therapy is being examined as a potential strategy for treating prostate cancer. Serotype 5 adenovirus (Ad.5) is routinely used as a vector for transgene delivery. However, the infectivity of Ad.5 is dependent on Coxsackie-adenovirus receptors (CARs); many tumor types show a reduction in this receptor in vivo, thereby limiting therapeutic gene transduction. Serotype chimerism is one approach to circumvent CAR deficiency; this strategy is used to generate an Ad.5/3-recombinant Ad that infects cancer cells through Ad.3 receptors in a CAR-independent manner. In this report, the enhanced transgene delivery and efficacy of Ad.5/3-recombinant virus was evaluated using an effective wide-spectrum anticancer therapeutic melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24). Our data show that in low CAR human prostate cancer cells (PC-3), a recombinant Ad.5/3 virus delivering mda-7/IL-24 (Ad.5/3-mda-7) is more efficacious than an Ad.5 virus encoding mda-7/IL-24 (Ad.5-mda-7) in infecting tumor cells, expressing MDA-7/IL-24 protein, inducing cancer-specific apoptosis, inhibiting in vivo tumor growth and exerting an antitumor 'bystander' effect in a nude mouse xenograft model. Considering the fact that Ad.5-mda-7 has shown significant objective responses in a phase I clinical trial for solid tumors, Ad.5/3-mda-7 is predicted to exert enhanced therapeutic benefit in patients with prostate cancer.

BISEN: Biochemical Simulation Environment.

SUMMARY: The Biochemical Simulation Environment (BISEN) is a suite of tools for generating equations and associated computer programs for simulating biochemical systems in the MATLAB computing environment. This is the first package that can generate appropriate systems of differential equations for user-specified multi-compartment systems of enzymes and transporters accounting for detailed biochemical thermodynamics, rapid equilibria of multiple biochemical species and dynamic proton and metal ion buffering. AVAILABILITY: The software and a user manual (including several tutorial examples) are available at bbc.mcw.edu/BISEN.

Frequency of major affective disorders in first-degree relatives of patients with type 2 diabetes mellitus.

BACKGROUND & OBJECTIVES: A genetic link between diabetes and depression has been proposed, but hardly explored. Data on family studies exploring relation between depression and diabetes are scanty. This study attempted to assess the prevalence of major affective disorders in first-degree relatives of patients with type 2 diabetes mellitus (T 2 DM). METHODS: Fifty probands with T 2 DM, in whom other psychiatric disorders had been excluded, were chosen. Morbid risks and prevalence figures for depression and mania were estimated in 481 first-degree relatives of these 50 probands using the family interview for genetic studies. RESULTS: Of the 481 first-degree relatives of probands, only six had affective disorders. The morbid risk for depression in first-degree relatives was 2.99 and 3.87 per cent, assuming age of risk at 15-60 and 15-50 yr respectively, while the morbid risk for mania was 0.59 and 0.77 per cent in these age groups. INTERPRETATION & CONCLUSION: The morbid risks/prevalence rates among first-degree relatives of probands with T2 DM were not higher than those of the general population rates derived from earlier Indian and western studies. This study did not demonstrate a family aggregation of affective disorders in patients with T 2 DM. Increased prevalence of affective disorders in diabetes could be due to non-genetic factors.

Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies.

Assessment of the rate of muscle oxygen consumption, UO(2m), in vivo during exercise involving a large muscle mass is critical for investigating mechanisms regulating energy metabolism at exercise onset. While UO(2m) is technically difficult to obtain under these circumstances, pulmonary oxygen uptake, VO(2p), can be readily measured and used as a proxy to UO(2m). However, the quantitative relationship between VO(2p) and UO(2m) during the nonsteady phase of exercise in humans, needs to be established. A computational model of oxygen transport and utilization--based on dynamic mass balances in blood and tissue cells--was applied to quantify the dynamic relationship between model-simulated UO(2m) and measured VO(2p) during moderate (M), heavy (H), and very heavy (V) intensity exercise. In seven human subjects, VO(2p) and muscle oxygen saturation, StO(2m), were measured with indirect calorimetry and near infrared spectroscopy (NIRS), respectively. The dynamic responses of VO(2p) and StO(2m) at each intensity were in agreement with previously published data. The response time of muscle oxygen consumption, tauUO(2m) estimated by direct comparison between model results and measurements of StO(2m) was significantly faster (P < 0.001) than that of pulmonary oxygen uptake, tauVO(2p) (M: 13 +/- 4 vs. 65 +/- 7 s; H: 13 +/- 4 vs. 100 +/- 24 s; V: 15 +/- 5 vs. 82 +/- 31 s). Thus, by taking into account the dynamics of oxygen stores in blood and tissue and determining muscle oxygen consumption from muscle oxygenation measurements, this study demonstrates a significant temporal dissociation between UO(2m) and VO(2p) at exercise onset.

Dopaminergic influence on thyrotropin secretion in primary hypothyroidism.

This study was conducted to assess the influence of dopamine on thyrotropin secretion in patients with primary hypothyroidism before and after optimized L-thyroxin replacement therapy. Thyrotropin responses to dopamine infusion (4 microg/kg/min over 3 hours) and IV metoclopramide (10 mg bolus), a dopamine receptor blocker were studied in 25 consecutive patients with primary hypothyroidism before and after achieving stable euthyroid state and compared with 15 normal age-matched controls. Thyrotropin response to both dopamine infusion (decremental) and IV metoclopramide bolus (incremental) was greater in patients with primary hypothyroidism than that in the control subjects. Thyrotropin response was greater in women than in men. The magnitude of decremental thyrotropin response to dopamine infusion and the incremental response to IV metoclopramide bolus significantly correlated with the basal T3 and T4 levels. Thyrotropin response was blunted to dopamine infusion but not to metoclopramide at follow-up after six-month replacement with L-thyroxin, and both the responses were comparable in women and men in patient group. We conclude that modulation of dopaminergic system by dopamine or by dopamine receptor blocker has a greater influence on thyrotropin secretion in patients with primary hypothyroidism than euthyroid normal subjects.

Presentation and outcome of rhino-orbital-cerebral mucormycosis in patients with diabetes.

AIM: To report presentation and outcome of rhino-orbital-cerebral mucormycosis (ROCM) exclusively in patients with diabetes mellitus. METHODS: Retrospective, non-comparative, interventional analysis of the medical records of 35 patients with ROCM among 22 316 patients with diabetes seen over the last 12 years. RESULTS: A cohort of 23 men and 12 women with a mean (SD) age of 47.3 (14.4) years (range 18-70 years) was studied. Five patients had type 1 diabetes mellitus, 29 had type 2 diabetes mellitus, and one had secondary diabetes. Nine patients had ROCM as the first clinical manifestation of diabetes. The mean (SD) blood glucose at presentation was 20.6 (8.3) mmol/l (range 10.0 to 53.3 mmol/l) and 17 patients had ketosis/ketoacidosis. Ophthalmic symptoms and signs were pronounced: external ophthalmoplegia (89%), proptosis (83%), visual loss (80%), chemosis (74%), and eye lid gangrene (14%). Non-ophthalmic manifestations included sinusitis (100%), nasal discharge/ulceration (74%), infranuclear VI nerve palsy (46%), palatal necrosis (29%), cerebral lobe involvement (20%), and hemiparesis (17%). Computed tomography/magnetic resonance imaging showed involvement of paranasal sinuses in all patients with ethmoid (86%) and maxillary (80%) sinuses being most frequently involved. Orbital involvement was observed in 80% of patients with cavernous sinus thrombosis in 11%, and internal carotid occlusion and hydrocephalus in 3% each. All were treated with amphotericin B (3-3.5 g) and 26 (74%) patients underwent appropriate surgery. Twenty one patients (68%) survived with a mean (SD) follow up of 39.6 (34.1) months (range 10 months to 11 years). Factors related to poor survival included delay in diagnosis and treatment (p<0.05), facial and/or eye lid gangrene (p<0.05), hemiplegia (p<0.05), cerebral invasion by mucorales (p<0.05), and treatment with amphotericin B alone (p<0.05). CONCLUSIONS: In patients with diabetes and ROCM, ROCM was the presenting manifestation in one fourth of the patients. Ophthalmic and extensive cerebral involvement predominated in the clinical picture. Delay in treatment due to late presentation and associated complications were major determinants of the survival outcome in these patients.

Radiation-induced brain disorders in patients with pituitary tumours.

Radiation-induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post-surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non-functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 +/- 8.3; median, 36) with a follow-up period of 6-96 months (mean, 18.3 +/- 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 +/- 13.4; median, 45), which was given in 15-30 fractions (mean, 18.6 +/- 5.0; median, 15) with 2.8 +/- 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 +/- 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 +/- 57.0; median, 57). The clinical spectrum of RIBD included new-onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic disorder in adults following pituitary irradiation have not been reported previously.

Plasma cortisol response to 1-24 adrenocorticotropin in patients with treated/untreated sellar & suprasellar mass lesions.

BACKGROUND & OBJECTIVES: One microgram short synacthene test is widely recommended as a screening test for evaluation of hypothalamo-pituitary-adrenocortical axis in patients with secondary adrenal insufficiency. Information on adequacy of cortisol response to this dose at different periods of the day in patients with hypothalamic-pituitary disorders is not available. Hence, this study was designed to assess the adequacy of cortisol response to 1 microg 1-24 adrenocorticotropin (ACTH) at 0800 h and 1600 h in patients with sellar and suprasellar mass lesions. METHODS: Thirty five consecutive patients with sellar and suprasellar mass lesions with mean age of 43.0+/-14.4 yr and 36 healthy controls with mean age of 32.3+/-9.0 yr were studied after obtaining informed consent. Maintenance doses of glucocorticoids in these patients were discontinued appropriately. On day 1, prestimulated and stimulated plasma cortisol samples at 0800 h and at 30 and 60 min following i.v. bolus of 1 microg 1-24 ACTH were collected. While on day 3, plasma cortisol samples were similarly collected at 1600 h. Cortisol estimation was done by a sensitive and specific radioimmunoassay. Stimulated plasma cortisol of 500 nmol/l or higher was defined as a normal response. RESULTS: In healthy controls, the prestimulated and peak cortisol levels at 0800 h (377.5+/-93.3 and 729.1+/-183.2 nmol/l) were higher (P<0.001 and P<0.01) than those at 1600 h (230.1+/-75.7 and 665.8+/-138.6 nmol/l). All subjects had a cortisol response of 500 nmol/l or higher in response to 1 microg 1-24 ACTH both at 0800 and 1600 h. In the patients' group, the prestimulated plasma cortisol at 0800 h (250.3+/-169.7 nmol/l) was higher (P<0.001) than that at 1600 h (166.3+/-128.9 nmol/l), while the peak cortisol response was comparable (P>0.05) in the morning as well as in the evening (490.9+/-309.4 vs 464.8+/-318.4). In 27 patients (77%) the morning and evening stimulated cortisol response to 1 microg 1-24 ACTH was consistent (normal in 13 and subnormal in 14) but was discrepant in the remaining 8 (23%). In 7 of these 8 patients, cortisol response was normal at 0800 h but not at 1600 h, while in only one, normal response was seen at 1600 h but not at 0800 h. INTERPRETATION & CONCLUSION: The demonstration of normal peak cortisol response to 1 microg 1-24 ACTH at 0800 h but not at 1600 h in substantial number of patients with sellar and suprasellar mass lesions suggests preference to morning for performing this test.