Glycogen synthase kinases 3α and 3β in cardiac myocytes: regulation and consequences of their inhibition

Inhibition of glycogen synthase kinase 3β (GSK3β) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3α (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3β in cardiac myocytes. Although endothelin increases phosphorylation of GSK3 and decreases its activity, the response is less than that induced by insulin (which does not promote cardiac myocyte hypertrophy). GSK3 phosphorylation induced by endothelin requires signalling through the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade and not the PKB/Akt pathway, whereas the reverse is true for insulin. Cardiac myocyte hypertrophy involves changes in morphology, and in gene and protein expression. The potent GSK3 inhibitor 1-azakenpaullone increases myocyte area as a consequence of increased cell length whereas phenylephrine increases both length and width. Azakenpaullone or insulin promotes AP1 transcription factor binding to an AP1 consensus oligonucleotide, but this was significantly less than that induced by endothelin and derived principally from increased binding of JunB protein, the expression of which was increased. Azakenpaullone promotes significant changes in gene expression (assessed by Affymetrix microarrays), but the overall response is less than with endothelin and there is little overlap between the genes identified. Thus, although GSK3 may contribute to cardiac myocyte hypertrophy in some respects (and presumably plays an important role in myocyte metabolism), it does not appear to contribute as significantly to the response induced by endothelin as has been maintained

Prevalence of and factors associated with pre-diabetes among adolescents in Eastern Sudan: a community-based cross-sectional study

Objectives: There is an increasing trend of pre-diabetes and diabetes mellitus (DM) among adolescents, and sub-Saharan Africa is no exception. However, few published data on pre-diabetes among adolescents in Sudan exist. We aimed to investigate the prevalence of and factors associated with pre-diabetes among adolescents in Eastern Sudan. Design: A community-based cross-sectional study was conducted from August to October 2023. Settings: This community-based study was conducted in Gadarif city, the capital of Gadarif state, Eastern Sudan. Participants: Adolescents (within the ages of 10–19 years). Main outcome measures: A questionnaire was used to collect socio-demographic information. Anthropometric and glycated haemoglobin (HbA1c) measurements were performed in accordance with standard procedures. Multivariate logistic regression analysis was performed. Results: Of the 387 enrolled adolescents, 207 (53.5%) were female and 180 (46.5%) were male. The median (IQR) age was 14.0 (12.0–16.0) years. 39.5% of the participants’ fathers were employed. The median (IQR) HbA1c was 5.5% (5.2%–5.8%). One-third (32.6%) of the adolescents had pre-diabetes or DM. Of the participants, 67.4%, 30.0% and 2.6% had no DM, pre-diabetes or type 2 DM, respectively. In the univariate analysis, the father’s employment (OR=1.60, 95% CI=1.03 to 2.50) was associated with increased odds of pre-diabetes; age, sex, parents’ education, the mother’s occupation, body mass index z-score, cigarette smoking and a family history of DM were not associated with pre-diabetes. In the multivariate analysis, the father’s employment (adjusted OR=1.70, 95% CI=1.03 to 2.50) was associated with increased odds of pre-diabetes. Conclusion: Pre-diabetes is a significant public health problem among adolescents in Eastern Sudan. The introduction of early screening programmes for pre-diabetes at the community level is recommended to halt the progression of pre-diabetes to DM and to deal with existing DM among adolescents

Cancer Risk Assessment and Geochemical Features of Granitoids at Nikeiba, Southeastern Desert, Egypt

Different rock types (syenogranite, alkali feldspar granite and quartz syenite intruded by microgranite dikes and quartz veins) were investigated in the Nikeiba region in Egypt. The main components of the studied intrusive rocks, comprised of granites and quartz syenite, are plagioclase, amphibole, biotite, quartz and K-feldspar in different proportions. Ground gamma ray measurements show that syenogranite, quartz syenite and microgranite dikes have the highest radioactivity (K, eU, eTh and their ratios) in comparison with alkali feldspar granite. Geochemically, syenogranite, alkali feldspar granite and quartz syenite are enriched with large-ion lithophile elements (LILE; Ba, Rb, Sr) and high field-strength elements (HFSE; Y, Zr and Nb), but have decreased Ce, reflecting their alkaline affinity. These rocks reveal calc–alkaline affinity, metaluminous characteristics, A-type granites and post-collision geochemical signatures, which indicates emplacement in within-plate environments under an extensional regime. U and Th are increased in syenogranite and quartz syenite, whereas alkali feldspar granite shows a marked decrease in U and Th. The highest average values of AU (131 ± 49 Bq·kg−1), ATh (164 ± 35) and AK (1402 ± 239) in the syenogranite samples are higher than the recommended worldwide average. The radioactivity levels found in the samples are the result of the alteration of radioactive carrying minerals found inside granite faults. The public’s radioactive risk from the radionuclides found in the investigated granitoid samples is estimated by calculating radiological risks. The excess lifetime cancer (ELCR) values exceed the permissible limit. Therefore, the granitoids are unsuitable for use as infrastructure materials. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Excess Lifetime Cancer Risk Associated with Granite Bearing Radioactive Minerals and Valuable Metals, Monqul Area, North Eastern Desert, Egypt

The present work is concerned with assessing the cancer risk contributed by the studied granite types including valuable metals, such as Cu, Au, and Ba mineralization, as well as radioactive-bearing mineralization, such as monazite and zircon, in south Monqul at Wadi Makhrag El Ebel, north Eastern Desert, Egypt. The mineralization analyses illustrated that copper mineralization containing chrysocolla and tenorite minerals were restricted to the alteration zone, especially (argillic, phyllic, and propylitic) in monzogranite. However, barite veinlets had an ENE–WSW trend, while gold mineralization was confined to quartz veins having NE–SW trends. Monazite and zircon are radioactive-bearing minerals recorded in monzogranite causing high radioactive zones in south Monqul. The radionuclide activity concentrations were detected in the studied monzogranites. The mean values of AU (103 ± 91 Bq kg−1), ATh (78 ± 19 Bq kg−1), and AK (1484 ± 334 Bq kg−1) in the monzogranite samples were higher than the recommended worldwide average. The change in radioactive-transporting minerals found inside granite faults caused the high amounts of radioactivity seen in the samples. Due to the monzogranites being applied in building materials, the radiological hazards were assessed by calculating risk indices such as annual effective dose (AED) and excess lifetime cancer risk (ELCR). The acceptable limit for the ELCR readings was surpassed. As a result, the investigated monzogranite samples are not suitable for use in infrastructure materials. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Changes in Renal Function in Elderly Patients Following Intravenous Iodinated Contrast Administration: A Retrospective Study

Background. Contrast-induced nephropathy (CIN) is a recognised complication of intravascular administration of iodinated contrast media (ICM). Previous studies suggest a higher incidence in the elderly, but no large study has assessed this to date. We set out to assess changes in creatinine in elderly inpatients following computed tomography (CT) examination and compare those who received intravenous contrast to those who did not. Methods. Using the Radiology Information System in two teaching hospitals, inpatients over the age of seventy who had a CT examination and a baseline creatinine were identified and their follow-up creatinine levels were analysed. Elderly inpatients who underwent a noncontrast CT over the same period were used as controls. Results. 677 elderly inpatients who received ICM were compared with 487 controls. 9.2% of patients who received ICM developed acute kidney injury (AKI) compared to 3.5% of inpatient controls (P<0.0001). Patients with higher baseline eGFR had a higher incidence of post-CT AKI. Conclusions. The incidence of post-CT AKI is higher in patients who received IV ICM compared to those who did not; the difference may be partly attributable to contrast-induced nephropathy. This suggests that the incidence of CIN in the elderly may not be as high as previously thought

Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect

Cerebral Venous Sinus Thrombosis, a Nonenhanced CT Diagnosis?

Purpose. Retrospectively evaluate the density of cerebral venous sinuses in nonenhanced head CTs (NCTs) and correlate these with the presence or absence of a cerebral venous sinus thrombus (CVST). Materials and Methods. Institutional review board approval was obtained and informed consent waived prior to commencing this retrospective study. Over a two-year period, all CT venograms (CTVs) performed at our institution were retrieved and the preceding/subsequent NCTs evaluated. Hounsfield Units (HUs) of thrombus when present as well as that of normal superior sagittal and sigmoid sinuses were measured. HU of thrombus was compared to that of normal vessels with and without standardisation to the average HU of the internal carotid arteries. Results. 299 CTVs were retrieved, 26 with a thrombus. Both raw and standardised HU measurements were significantly higher in CVST (p<0.0001) compared to normal vessels. Both raw and standardised HUs are good predictors of CVST. A HU of ≥67 and a standardised measurement of ≥1.5 are associated with high probability of CVST on NCT. Conclusion. Cerebral venous sinus HU measurements may help improve sensitivity and specificity of NCT for venous sinus thrombosis and avoid potentially unnecessary follow-up examinations