Tankyrase: a promising therapeutic target with pleiotropic action.

Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) enzymes belong to the poly (ADP-ribose) polymerase (PARP) family participates in process of poly-ADP-ribosylation of different target proteins which leads to ubiquitin-mediated proteasomal degradation. Tankyrases are also involved in the pathophysiology of many diseases, especially cancer. Their functions include cell cycle homeostasis (primarily in mitosis), telomere maintenance, Wnt signaling pathway regulation, and insulin signaling (particularly GLUT4 translocation). Studies have implicated that genetic changes, mutations in the tankyrase coding sequence, or up regulation and down regulation of tankyrase are reflected in the numerous disease conditions. Investigations are pursued to develop putative molecules that target tankyrase in various diseases such as cancer, obesity, osteoarthritis, fibrosis, cherubism, and diabetes, thereby providing a new therapeutic treatment option. In the present review, we described the structure and function of tankyrase along with its role in different disease conditions. Furthermore, we also presented cumulative experimental evidences of different drugs acting on tankyrase.

Utility of dynamic susceptibility contrast MRI for differentiation between paragangliomas and meningiomas in the cerebellopontine angle and jugular foramen region.

PURPOSE: Differentiation of paragangliomas and meningiomas can be a challenge. This study aimed to assess the utility of dynamic susceptibility contrast perfusion MRI (DSC-MRI) to distinguish paragangliomas from meningiomas. METHODS: This retrospective study included 40 patients with paragangliomas and meningiomas in the cerebellopontine angle and jugular foramen region between March 2015 and February 2022 in a single institution. Pretreatment DSC-MRI and conventional MRI were performed in all cases. Normalized relative cerebral blood volume (nrCBV), relative cerebral blood flow (nrCBF), relative mean transit time (nrMTT), and time to peak (nTTP) as well as conventional MRI features were compared between the 2 tumor types and between meningioma subtypes as appropriate. Receiver operating characteristic curve and multivariate logistic regression analysis were performed. RESULTS: Twenty-eight meningiomas including 8 WHO grade II meningiomas (12 males, 16 females; median age 55 years) and 12 paragangliomas (5 males, 7 females; median age 35 years) were included in this study. Paragangliomas had a higher rate of cystic/necrotic changes (10/12 vs 10/28; P = 0.014), a higher rate of internal flow voids (9/12 vs 8/28; P = 0.013), higher nrCBV (median 9.78 vs 6.64; P = 0.04), and shorter nTTP (median 0.78 vs 1.06; P < 0.001) than meningiomas. There was no difference in conventional imaging features and DSC-MRI parameters between meningioma subtypes. nTTP was identified as the most significant parameter for the 2 tumor types in the multivariate logistic regression analysis (P = 0.009). CONCLUSIONS: In this small retrospective study, DSC-MRI perfusion differences were observed between paragangliomas and meningiomas, but not between grade I and II meningiomas.

Precise differentiation between jugular foramen paragangliomas and metastases: utility of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: This study tested the utility of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE-MRI) in differentiating paragangliomas and metastases in the jugular foramen in combination with conventional imaging. METHODS: Forty-nine consecutive patients with paragangliomas or metastases between January 2015 and April 2022 were included in this retrospective study. All patients had pretreatment DWI and DCE-MRI. Between paragangliomas and metastases, normalized apparent diffusion coefficient (nADCmean) and DCE-MRI parameters were compared along with conventional imaging features (enhancement pattern, presence of flow voids, cystic/necrotic change, and bone erosion). The diagnostic performance was tested using receiver operating characteristic (ROC) analysis. RESULTS: Thirty-five paragangliomas (5 male; median 49 years) and 14 metastases (9 male; median 61 years) were analyzed. The most common 3 primary cancers included 4 lung cancers, 3 breast cancers, and 3 melanomas. The presence of flow void was significantly different between paragangliomas and metastases (21/35 vs 2/14; P = 0.0047) in conventional imaging features, while fractional plasma volume (Vp) was significantly different between the two tumor types (median 0.46 vs 0.19; P < 0.001) in DWI and DCE-MRI parameters. The areas under the ROC curves (AUCs) of the presence of flow void and Vp were 0.72 and 0.93, respectively. The AUC of the combination of the presence of flow void and Vp was 0.95 and significantly improved compared to that of the presence of flow void (P < 0.001). CONCLUSION: Adding DCE-MRI to the head and neck protocol can aid in the precise differentiation between jugular foramen paragangliomas and metastases.

Luteinizing hormone ß-subunit deficiency: Report of a novel LHB likely pathogenic variant and a systematic review of the published literature.

CONTEXT: Selective deficiency of ß-subunit of luteinizing hormone (LHB) is a rare disease with scarce data on its characteristics. OBJECTIVES: To describe a male with LHB deficiency and systematically review the literature. DESIGN AND PATIENTS: Description of a male patient with LHB deficiency and a systematic review of LHB deficiency patients published to date (10 males and 3 females) as per PRISMA guidelines. RESULTS: A 36-year-old Asian Indian male presented with infertility. On evaluation, he had sexual maturity of Tanner's stage 3, low testosterone (0.23 ng/ml), low LH (0.44 mIU/ml), high follicle-stimulating hormone (FSH, 22.4 mIU/ml), and a novel homozygous missense likely pathogenic variant (p.Cys46Arg) in LHB. In the molecular dynamics simulation study, this variant interferes with heterodimerization of alpha-beta subunits. Eleven males with pathogenic variants in LHB reported to date, presented at a median age of 29 (17-38) years, most commonly with delayed puberty. Clinical and biochemical profiles were similar to those of our patient. In the majority, testosterone monotherapy modestly increased testicular volume whereas human chorionic gonadotropin (hCG) monotherapy also improved spermatogenesis. In females, oligomenorrhoea after spontaneous menarche was the most common manifestation. Ten pathogenic/likely pathogenic variants (three in-frame deletions, three missense, two splice-site, one nonsense, and one frameshift variants) have been reported in nine index patients. CONCLUSION: We report a novel likely pathogenic LHB variant in an Asian Indian patient. The typical phenotype in male patients with LHB deficiency is delayed puberty with low testosterone, low LH, and normal to high FSH and hCG monotherapy being the best therapeutic option.

Comparative Evaluation of Aldose Reductase Inhibition in Polycystic Ovarian Syndrome-Induced Rats.

Polycystic ovary syndrome (PCOS) represents a spectrum of disorders, associated with hyperandrogenism, oligoanovulation, and polycystic ovaries. Aldose reductase (AR), a rate-limiting enzyme of polyol pathway, is responsible for maintenance of intracellular osmotic balance, facilitation of oocyte development, and organization of the granulosa cells in the ovary. Cyclic changes in the aldose reductase level were found during the 4-5 days estrus cycle in rat, which is regulated by gonadotropin-releasing hormone (GnRH). Irregular GnRH secretion in PCOS patients may lead to altered aldose reductase expression and ovarian dysfunction. Treatment with a novel AR inhibitor, fidarestat, has been reported to improve erythrocyte sorbitol content in diabetic patients. Hence, the potential role AR in pathogenesis of PCOS was investigated by inhibiting AR with fidarestat in PCOS-induced rats. Pre-pubertal female Sprague-Dawley rats were divided into five groups. PCOS is induced either by administering letrozole or by feeding high-fat diet for 90 days. After induction of PCOS, fidarestat treatment was given for 28 days and various parameters were measured. In PCOS-induced rats, parameters like food intake, body weight, insulin, OGTT, triglycerides, cholesterol, prolonged diestrus phase, ovary weight, and immunohistological localization AR were found to be significantly altered. Fidarestat treatment significantly improved ovary weight, ovarian aldose reductase localization in PCOS-induced rats. Improvement in all these parameters suggest involvement of aldose reductase in the pathogenesis of PCOS.

Assessment of potential drug-drug interactions among outpatients in a tertiary care hospital: focusing on the role of P-glycoprotein and CYP3A4 (retrospective observational study).

Background: Selecting a medicine has a significant impact on the quality of therapy including efficacy and safety. P-glycoprotein and CYP3A4 share several common substrates known as bi-substrates. Both play major role in the pharmacokinetics and pharmacodynamics when over or under expressed. Objective: The study aimed to assess the Drug-Drug Interaction (DDI) related to P-glycoprotein (P-gp) and Cytochrome P450-3A4 (CYP3A4), to predict their clinical outcomes and also to discover prospective predictors of pDDIs. Methods: The subjects in this retrospective study ranged in age from 18 to 95 years with polypharmacy prescriptions. Information was gathered through patient medical records. Based on Micromedex and previous literature studies, medications prescribed to the patients were observed for pDDIs according to risk rating scale for drug interactions. Results: A total of 504 patients (160 males and 344 females) were included in the study. The mean of pDDI seen in the patients was 1.66 ± 1.48 and total 825 pDDIs were discovered. The factors significantly associated with having ≥1 pDDIs included: taking ≥5 medicines (OR 1.747), increased age (OR 1.026) increased comorbidities (OR 1.73). Conclusion: In prescriptions, a considerable number of probable DDI were discovered. Therefore, careful selection of drugs and identification of mechanisms for DDI is needed to lower the frequency of pDDI.

Advanced MRI to differentiate schwannomas and metastases in the cerebellopontine angle/internal auditory canal.

BACKGROUND AND PURPOSE: Differentiating schwannomas and metastases in the cerebellopontine angles (CPA)/internal auditory canals (IAC) can be challenging. This study aimed to assess the role of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) to differentiate schwannomas and metastases in the CPA/IAC. METHODS: We retrospectively reviewed 368 patients who were diagnosed with schwannomas or metastases in the CPA/IAC between April 2017 and February 2022 in a single academic center. Forty-three patients had pretreatment DWI and DCE-MRI along with conventional MRI. Normalized mean apparent diffusion coefficient ratio (nADCmean) and DCE-MRI parameters of fractional plasma volume (Vp), flux rate constant (Kep), and forward volume transfer constant were compared along with patients' demographics and conventional imaging features between schwannomas and metastases as appropriate. The diagnostic performances and multivariate logistic regression analysis were performed using the significantly different values. RESULTS: Between 23 schwannomas (15 males; median 48 years) and 20 metastases (9 males; median 61 years), nADCmean (median: 1.69 vs. 1.43; p = .002), Vp (median: 0.05 vs. 0.20; p < .001), and Kep (median: 0.41 vs. 0.81 minute-1 ; p < .001) were significantly different. The diagnostic performances of nADCmean, Vp, and Kep were 0.77, 0.90, and 0.83 area under the curves, with cutoff values of 1.68, 0.12, and 0.53, respectively. Vp was identified as the most significant parameter for the tumor differentiation in the multivariate logistic regression analysis (p < .001). CONCLUSIONS: DWI and DCE-MRI can help differentiate CPA/IAC schwannomas and metastases, and Vp is the most significant parameter.

Effect of Vitex negundo L. seeds in letrozole induced polycystic ovarian syndrome.

The clinical management of PCOS is multifaceted but often unsatisfactory. The aim of the current study is to evaluate the effect of Vitex negundo L. in the letrozole-induced polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into six groups, each containing 6 animals. Group I (Control) daily received 1% carboxymethylcellulose (CMC) suspension as a vehicle control. Letrozole (1 mg/kg) was administered per orally (p.o) for a period of 21 days for the induction of PCOS in Group II to VI. PCOS induced animals were treated with aqueous (Group III - 200 mg/kg and IV- 400 mg/kg) and hydroalcoholic extract (Group V- 200 mg/kg and VI- 400 mg/kg) of Vitex negundo up to 66 days using 0.5% w/v CMC as the vehicle. Body weight and estrous cycle phase were measured every day. Blood samples were collected on 0, 21 and 66 days for the measurement of fasting blood glucose, lipid profile, LH, FSH and hormonal level. Oral glucose tolerance test was performed to study insulin resistance effect. Toxicity markers; SGOT, SGPT, and creatinine also measured at the end of the study. The administration of Letrozole led to an abnormality in serum sex steroid profile, lipid profile, glucose and estrous cycle. It was able to successfully exert its protective effect by restoring parameters to the normal level and disappearance of cysts in ovaries. This can be attributed to phyto-components present in the extract. The aqueous and hydro-alcoholic extracts of seeds of Vitex negundo showed significant amelioration of Letrozole induced PCOS.

Evaluation of ovarian and metabolic effects of GnRH modulators in two rat models of polycystic ovary syndrome.

Gonadotropin-releasing hormone (GnRH) modulators are widely used in numerous reproductive conditions including infertility. Several clinical studies showed mixed results regarding the efficacy of GnRH modulators in patients with polycystic ovary syndrome (PCOS). Along with this, few preclinical studies focus on the effect of GnRH modulators in PCOS-induced animals. Therefore, the present study was designed to study the effect of leuprolide and cetrorelix on hormonal, metabolic, and menstrual dysfunction PCOS rats. Prepubertal female rats were divided into four groups: Group I received a normal pellet diet and Groups II, III, and IV received 40% high-fat diet for 105 days. Similarly, adult female rats were divided into four groups: Group I received 1% carboxymethylcellulose (CMC) and Groups II, III, and IV received letrozole (1 mg/kg, per oral [p.o.] in 1% CMC) for 21 days. Thereafter, leuprolide (2.5 µg/rat, s.c.) and cetrorelix (10 µg/kg, subcutaneous [s.c.]) treatment were given to Group III and Group IV animals, respectively, for 21 days. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, ovarian histopathological changes, and LHR and FSHR expressions were measured. Treatment with leuprolide and cetrorelix did not improve glucose intolerance, insulin level, insulin sensitivity indices, sex hormone levels, lipid profile, and estrus cycle. Only testosterone level, total cholesterol level, and follicular development were improved. Therefore, it was concluded that both leuprolide and cetrorelix showed improvement in follicular development, which could be helpful for improving fertility in PCOS.

Insulin Sensitizers Modulate GnRH Receptor Expression in PCOS Rats.

BACKGROUND: Insulin sensitizers like metformin and pioglitazone are clinically used since last decades for the treatment of PCOS, but their efficacy and possible role in PCOS patients remains questionable. Also, the mechanism by which these insulin sensitizers show effect is not clear. AIM OF THE STUDY: To evaluate the effect of metformin and pioglitazone on leutinizing hormone and follicle stimulating hormone receptor mRNA expression, hyperandrogenism and insulin resistance in high fat diet induced and letrozole induced PCOS in rats. METHODS: Pre-pubertal female rats were divided into four groups: group I received normal pellet diet and group II, III and IV received high fat diet. After 105 d of dietary manipulation, metformin and pioglitazone treatment was given to group III and group IV animals respectively for 21 d. Similarly, adult female rats were divided into four groups: group I received 1% carboxymethyl cellulose (CMC) and group II, III, IV received letrozole for 21 d. After 21 d of letrozole administration, metformin and pioglitazone treatment was given to group III and group IV animals respectively for 21 d. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, leutinizing hormone receptor and follicle stimulating hormone receptor mRNA expression was measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary. RESULTS AND CONCLUSION: Metformin and pioglitazone treatment improve both metabolic and reproductive parameters of PCOS including hyperinsulinemia and hyperandrogenism. LH receptor and FSH receptor mRNA expression were altered by pioglitazone and metformin treatment.

Pyogenic Ventriculitis and Meningitis Caused by Streptococcus Acidominimus in Humans: A Case Report.

BACKGROUND Streptococcus acidominimus, which belongs to the viridans streptococci group, is rarely considered pathogenic in humans. However, over the past 10 years, this bacterium has been reported to cause serious infections in humans, particularly among the critically ill. This article is the first case report of pyogenic ventriculitis (PV) and meningitis caused by S. acidominimus in North America. CASE REPORT A 49-year-old Asian male presented to the emergency department with complaints of a headache, fever greater than 37.8°C (100°F) and confusion, of approximately 3 days duration. He was unable to speak coherently or follow approximately half of the given commands. He appeared ill; an intracranial infection was suspected. Magnetic resonance imaging of the brain showed: 1) infected proteinaceous material and pus-like material throughout the cerebral sulci and in the occipital horns of both lateral ventricles, 2) ependymal signal abnormality of the posterolateral margin of the occipital horn of the left lateral ventricle, and 3) early hydrocephalus suggestive of ventriculitis and meningitis. The blood and cerebrospinal fluid cultures were positive for S. acidominimus. The patient improved with minimal deficits after 6 weeks of IV ceftriaxone without requiring a neurosurgical intervention, such as an intraventricular drain or neuroendoscopic surgery. CONCLUSIONS PV and meningitis caused by S. acidominimus are rare but potentially fatal intracranial infections. Therefore, despite the risk of generalizing, our case report suggests that PV and meningitis caused by S. acidominimus can be effectively treated with a prompt and prolonged course of IV ceftriaxone without neurosurgical intervention.

High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome (PCOS) in rats.

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo-anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported that PCOS often starts with menarche in adolescents. Presently available animal model focuses on ovarian but not metabolic features of PCOS. Therefore, we hypothesized that high-fat diet feeding to pre-pubertal female rats results in both reproductive and metabolic features of PCOS. Pre-pubertal female rats were divided into two groups: group I received normal pellet diet and group II received high-fat diet (HFD). In the letrozole study, adult female rats were divided into two groups: group I received 1% carboxy methyl cellulose and group II received 1 mg/kg letrozole orally. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, luteinizing hormone (LH) receptor and follicle-stimulating hormone receptor expression were measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Feeding of HFD gradually increase glucose intolerance and fasting insulin levels. Triglyceride level was higher in HFD study while total cholesterol level was higher in the letrozole study. Alteration in testosterone and estrogen levels was observed in both studies. LH receptor expression was upregulated only in HFD study. Histopathological changes like increase cystic follicle, diminished granulosa cell layer and thickened theca cell layer were observed in letrozole as well as HFD study. High-fat diet initiated at pre-puberty age in rats produces both metabolic disturbances and ovarian changes similar to that observed clinically in PCOS patients. Letrozole on the other hand induces change in ovarian structure and function.

Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund's adjuvant-induced arthritic rats: involvement of cellular inflammatory mediators and other biomarkers.

Alteration of microbiota is related with rheumatoid arthritis (RA) and administration of certain probiotics showed an improvement in RA. The present study was designed to find out the anti-arthritic activity of cell wall content of Lactobacillus plantarum in complete Freund's adjuvant (CFA)-induced arthritis in rats. Freund's adjuvant was injected into the left footpad in female rats on day 0 and dexamethasone (1 mg kg-1, s.c.) & cell wall content of L. plantarum (105, 107, and 109 cfu/animal, s.c.) treatment were given from day 7 to 21. The change in body weight, paw volume and arthritic index, joint stiffness, gait test, mobility test, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, serum rheumatoid factor (RF), and serum TNF-α was measured on day 21. Cell wall content of L. plantarum treated animals showed improvement in all the parameters as compared to that in CFA-treated animals and exert anti-arthritic activity.

Effect of metformin on clinical, metabolic and endocrine outcomes in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials.

OBJECTIVE: Metformin has been used as a treatment option for polycystic ovary syndrome (PCOS) since 1994; however, more than a hundred randomized clinical trials have reported controversial results regarding the efficacy of metformin in PCOS. This could be due to the small sample size and high variability in methodology between studies. The objective of the present meta-analysis was to determine the effect of metformin on clinical, metabolic, and endocrine outcomes compared to placebo in PCOS women. METHODS: Randomized controlled trials evaluating the efficacy of metformin were identified using a literature search in PubMed. Bibliographies of relevant studies were also screened to identify additional studies. Data was extracted from included studies and analyzed using RevMan software 5.3 from the Cochrane Collaboration. MAIN OUTCOME MEASURES: Clinical outcomes included body mass index, waist to hip ratio, systolic and diastolic blood pressure and Ferriman-Gallway score. Metabolic outcomes included total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, fasting blood glucose, fasting insulin levels, glucose insulin ratio, HOMA-IR and QUICKI. Endocrine outcomes such as serum testosterone, free testosterone, free androgen index, serum sex hormone binding globulin, dehydroepiandrosterone sulfate, luteinizing hormone, follicle stimulating hormone, LH/FSH ratio, estradiol, and progesterone levels. CONCLUSION: Metformin showed significant improvement in clinical outcomes but not in metabolic and endocrine outcomes in PCOS women; however, heterogeneity between studies was found to be moderate to high.

Chemopreventive effect of a novel, selective TACE inhibitor on DMBA- and TPA-induced skin carcinogenesis.

UNLABELLED: Abstract Context: Tumor necrosis factor (TNF)-α, a potent proinflammatory cytokine, plays a major role in the pathogenesis of cancer. TNF-α converting enzyme (TACE) mediates processing and release of biologically active TNF-α. OBJECTIVE: We aimed to investigate the effect of a novel, selective TACE inhibitor (compound 11p) on skin inflammation and associated tumorigenesis in mice. METHODS: Skin edema was induced in mice by dermal application 12-O-tetradecanoylphorbol-13-acetate (TPA) solution in acetone on to the ear and the effect of post-treatment of compound 11p (topical application) was evaluated. Edema and inflammation was assessed by measuring ear thickness, weight of skin punch and cytokine levels. Skin cancer in mice was initiated by single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by repeated TPA application for 20 weeks. The effect of compound 11p on papilloma incidence and multiplicity was evaluated. RESULTS: Treatment with compound 11p strongly suppressed TPA-induced elevation in skin thickness and weight. A dose-dependent suppression in TPA-mediated TNF-α, IL-6, IFN-γ, IL-17 and PGE2 levels which was associated with a decrease in infiltration of inflammatory cells was also observed with the treatment. Moreover, compound 11p treatment delayed the onset, markedly reduced the papilloma incidence and multiplicity persuaded by DMBA and TPA. DISCUSSION AND CONCLUSION: These findings suggest that selective blockade of TACE suppresses TPA-induced epidermal hyperplasia, inflammatory cell infiltration and cytokine level. Inhibition of inflammatory events related to tumor growth might have led to the anti-tumor effect in mouse skin cancer model induced by DMBA and TPA.

Physicochemical and structural characterization of iron-sucrose formulations: a comparative study.

Intravenous polynuclear iron formulations are vital components in the treatment of iron deficiency anemia associated with chronic kidney disease as well as other diseases associated with gastro-intestinal and cardio-vascular system. Intravenous iron preparations consist of iron-carbohydrate nanoparticles with iron-oxyhydroxide as a core covered by carbohydrate shell. These preparations should be very well characterized in terms of their physicochemical properties and pharmacological profile in order to establish safety and efficacy. The present research work was aimed to physicochemically characterize a new generic iron-sucrose preparation (IS-Claris) and establish its equivalency with the reference product (Venofer®). Various analytical techniques including gel permeation chromatography (GPC), mass spectroscopy (MALDI-TOF), absorption spectroscopy, X-ray diffraction analysis (XRD), nuclear magnetic resonance spectroscopy (proton and (13)C NMR), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA) were employed. It was observed that the specifications of IS-Claris obtained through these analyses reflect those of Venofer® and hence the two formulations were considered comparable.

Sonographically guided lumbar puncture in pediatric patients.

Our aim with this study was to develop a user-friendly method for pediatric sonographically guided lumbar punctures so that we can visualize intrathecal anatomy, confirm intrathecal injection at the time of injection, and, most importantly, avoid ionizing radiation to a child's already radiosensitive pelvis. Sonographically guided lumbar puncture was prospectively performed in children aged 7 weeks to 16 years. All attempts (n = 9) were successful. We were able to identify relevant anatomy (including the conus in children 10 years and younger), confirm intrathecal injection, visualize intrathecal hematoma, and avoid radiation. Sonography is a promising modality for image-guided lumbar punctures without radiation in children.

Supratentorial neurenteric cyst mimicking hydatid cyst: A case report and literature review.

Neurenteric (NE) cysts are uncommon congenital cysts of endodermal origin. These cysts are commonly encountered in the posterior fossa surrounding the brain stem structures. We present a case of pathologically proven supratentorial NE cyst that mimicked a hydatid cyst in its clinical presentation and imaging appearance. Including this pathology in the differential diagnosis of supratentorial cystic lesions is important due to the differences in medical and surgical management.

Differentiation of benign and malignant neck pathologies: preliminary experience using spectral computed tomography.

PURPOSE: The objective of this study was to evaluate spectral Hounsfield unit (HU) curves and effective Z (atomic number) generated on dual-energy gemstone spectral imaging computed tomography (CT) in the differentiation of benign and malignant neck pathologic findings. METHODS: This was a retrospective review of 38 patients who underwent neck CT on a gemstone spectral imaging dual-energy CT (Lightspeed CT750 HD 64-slice CT scanner; GE Medical Systems, Milwaukee, Wis) from November 2009 to June 2012 with identifiable masses. One board-certified radiologist placed regions of interest within the mass (19 benign, 19 malignant) and in paraspinal muscles (PSMs) to create 2 spectral HU curves in each patient. The curve parameters compared between the benign and malignant groups included range (conceptually, the difference between the highest and lowest HU), asymptote, decay, and the differences and ratios (of lesion to PSM) of each of these 3 parameters. A logistic regression model was built with these parameters and effective Z. RESULTS: The difference in ranges (between lesion and PSM) was the best predictor of malignancy, with a threshold of 75 or greater demonstrating 95% sensitivity, 89% specificity, and 91.8% area under the curve (AUC). Adding other spectral HU parameters and effective Z to the model did not substantially increase the AUC (93.3%, difference between the 2 models not statistically significant, P > 0.25). The effective Z showed a 79.9% AUC with 68% sensitivity and 68% specificity at an 8.80 cutoff. CONCLUSIONS: The spectral HU curve is promising for differentiating benign and malignant neck pathologic findings, with the difference in range between the lesion and PSM showing the best predictive value.

Treatment with exendin-4 improves the antidiabetic efficacy and reverses hepatic steatosis in glucokinase activator treated db/db mice.

The glucokinase activators improve the fasting as well as postprandial glucose control and are important investigational drugs for the treatment of diabetes. However, recent studies have implicated that continuous activation of glucokinase with a small molecule activator can increase hepatic triglycerides and the long term glucose control is not achieved. In this study, we investigated the effect of combination of glucokinase activator (GKA, Piragliatin) with GLP-1 receptor agonist exendin-4 (Ex-4) in male db/db mice. Twelve weeks combination treatment in the db/db mice resulted in a significant decrease in body weight gain, food consumption, random glucose and %HbA1c. The decrease in serum glucose and %HbA1c in combination group was more profound and significantly different than that of individual treatment (GKA or Ex-4) group. GKA treatment increased hepatic triglycerides, whereas combination of Ex-4 with GKA attenuated hepatic steatosis. The combination of GKA with Ex-4 reduced the hepatic lipid accumulation, improved the insulin sensitivity, and reduced hepatic glucose production in db/db mice. Overall, our data indicate that combination of GKA and GLP-1 receptor agonist Ex-4 improves glucose homeostasis, shows antiobesity activity, without causing harmful side effects like fatty liver.