Regulation of IL-2 beta receptor expression and beta-chain mRNA by human thymocytes.

The high affinity form of the human IL-2 receptor (IL-2R) has two known components, the IL-2R alpha (p55) and the IL-2R beta chain (p75). We have previously shown that recombinant IL-2 (rIL-2) could induce the expression of the alpha-chain (p55) on T cells and thymocytes, and increase this expression following suboptimal activation with concanavalin A (Con A) in combination with IL-2. An increase in the accumulation of IL-2R alpha-specific mRNA induced by rIL-2 in T cells and thymocytes had also been documented. We report here that the expression of IL-2R beta on the cell surface can be demonstrated on human thymocytes by the binding of Mik beta1, a MoAb directed against an epitope of the beta-chain. The IL-2R beta chain is constitutively expressed on freshly isolated thymocytes; this expression can be increased in thymocytes activated with Con A in combination with IL-2 or tetradecanoylphorbol 13-acetate (TPA). Blocking the formation of high affinity receptors with a MoAb directed against the alpha-chain of the receptor results in an increase in the display of IL-2R beta as evidenced by binding of MoAb Mik beta1. The accumulation of IL-2R-beta-specific mRNA is observed in freshly isolated thymocytes and it is increased in thymocytes cultured with rIL-2 alone, with Con A, and further enhanced by the addition of rIL-2 in combination with Con A or with TPA. Cyclosporine (CsA), which inhibits the accumulation of lymphokine-specific mRNA of thymocytes, does not inhibit the induction of the accumulation of IL-2R beta-specific mRNA. This is analogous to its effect on the expression of the alpha-chain (p55), and the accumulation of alpha-chain-specific mRNA.     

Correlation between Karnofsky Performance Status Scale and Short-Form Health Survey in patients on maintenance hemodialysis

BACKGROUND: Assessment of quality of life is vital inmonitoring response to various treatment measures. Various instruments, which include both generic and disease-specific instruments, are used in the assessment of health-related quality of life (HRQOL). In this study, we compare two commonly used generic instruments. OBJECTIVES: The objective of this study was to compare two generic instruments, the Karnofsky Performance Status Scale and the SF-36 Health Survey in hemodialysis (HD) patients. The study also aims to find out the association (if any) between HRQOL scores using these two scales and various clinical and biochemical parameters. MATERIALS AND METHODS: Sixty-two maintenance HD patients were recruited after informed consents were obtained. Detailed sociodemographic data was obtained. They were assessed during their regular HD sessions. Serum chemistry (which included serum urea, creatinine, Na+, K+, HCO3-, Ca2+, Po4(2-)), albumin, globulin, total protein and hemoglobin (g/dl) were assessed in all the patients. Adequacy of HD was assessed using second-generation Daugirdais formula. HRQOL was assessed using the Karnofsky and SSF-36 instruments and the scores collated and compared. Data was analyzed using SPSS version 10. RESULTS: Fifty-five patients completed the study (27 males and 28 females, mean age 40.76 +/- 11.05 years and age range of 20-65 years). There was a significant positive correlation between Karnofsky scores and all eight SF-36 domains, but only physical functioning, social functioning and role limitation due to emotional problems maintained the significance on multiple regression analysis. The serum creatinine and hemoglobin postively correlated with physical function, bodily pain, social functioning and Karnofsky scores. Age of the patients correlated negatively with two SF-36 dimensions (physical functioning and role limitation due to physical fitness) and Karnofsky scores. CONCLUSION: This study revealed a good correlation between Karnofsky performance status scale and the short-form (SF36) health survey in this Egyptian population. Age, serum creatinine and hemoglobin significantly influence quality of life in this HD patient population.     

ROLE OF ACULASER THERAPY IN CEREBRAL PALSY CHILDERN （INITIAL DATA ＆ RESULTS）

1　BACKGROUNDTheincidenceofCPis 0 .7per 1 0 0 0livebirths[1 ] .Becausecerebralpalsyinfluencesthewaychildrendevelop,itoftenresultsindevelop mentaldisability .Today ,more peoplehavecerebralpalsythananyotherdevelopmentaldis ability ,includingDownsyndrome,epilepsy ,andautism .Accordingtoasurveyconductedin1 986,2 .6%ofthepopulationofPakistaniaredisabled (includingbothphysicalandmentaldis abilities) .Childrenbetween 0～1 4 yearsinageconstitute 40 %ofthedisabled populationinPakistan .Routineme…     

Face and brow presentation in northern Jordan, over a decade of experience

BACKGROUND: Malpresentation is a deviation from the normal presentation, which occurs in approximately 5% of labours (Seeds and Cefalo in Clin Obstet Gynaecol 25:145-156, 1982). The commonest form of malpresentation at delivery is breech presentation followed by face and brow presentation. OBJECTIVES: To review the incidence and management of face and brow presentation in north of Jordan. MATERIALS AND METHODS: This was a retrospective review of the experience of face and brow presentation deliveries in the two main civil hospitals in north of Jordan between 1995 and 2005. RESULTS: The incidence of face and brow presentation was 1 in 813 and 1 in 1,689 deliveries, respectively. There was no significant increase in the incidence of prematurity nor very low birth weight and no higher incidence of postmaturity among those delivered by face or brow in the same period. All the foetuses presenting by the brow and by face (mentoposterior) and only 16.7 % of foetuses presenting by face (mentoanterior) were delivered by caesarian section. CONCLUSION: The incidence of face and brow presentation was 1 in 813 and 1 in 1,689 deliveries, respectively. All the babies presenting by brow presentation did undergo caesarean section. The management of face and brow presentation is heading towards a safe delivery and not merely to accomplish vaginal delivery.     

Effects on physiologic measures of appetite from intragastric balloon and endoscopic sleeve gastroplasty: results of a prospective study

Background:Endoscopic bariatric therapies can help address widening management gaps in obesity. Their ability to facilitate weight loss is largely tied to influences on appetite through perturbations of gastric emptying and accommodation. As these tools gain traction in obesity therapy, their physiologic underpinnings require exploration, which may enhance efficacy, tolerance, and patient-tailored care.Methods:We prospectively assessed consecutive subjects with fluid-filled intragastric balloons (IGBs) (n = 18) placed between October 2016 and June 2017 or underwent endoscopic sleeve gastroplasty (ESG) (n = 23) from March 2018 to June 2018. Patients underwent physiologic appraisal at 3 months with ¹³C-spirulina-based gastric emptying breath test to determine time to half emptying (T50), as well as maximum tolerated volume (MTV) of a standard nutrient drink test. Changes in T50 and MTV at 3 months were compared with percent total body weight loss (%TBWL) at 3 and 6 months using best-fit linear regression.Results:The change in T50 at 3 months correlated with %TBWL at 3 months for IGB (P = 0.01) and ESG (P = 0.01) but with greater impact on %TBWL in IGB compared to ESG (R² = 0.42 vs. 0.26). Change in T50 at 3 months was predictive of weight loss at 6 months for IGB (P = 0.01) but not ESG (P = 0.11). ESG was associated with greater decrease in MTV compared to IGB (340.25 ± 297.97 mL vs. 183.00 ± 217.13 mL, P = 0.08), indicting an enhanced effect on satiation through decreased gastric accommodation. Changes in MTV at 3 months did not correlate with %TBWL for either IGB (P = 0.26) or ESG (P = 0.49) but trended toward significance for predicting %TBWL at 6 months for ESG (P = 0.06) but not IGB (P = 0.19).Conclusion:IGB and ESG both induce weight loss but likely through distinct gastric motor function phenotypes, and gastric emptying may predict future weight loss in patients with IGB.     

Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is partially involved in the pathogenesis of cispaltin-induced nephrotoxicity.     

An update on therapies for the treatment of diabetes-induced osteoporosis

Introduction: Currently, 424 million people aged between 20 and 79 years worldwide are diabetic. More than 25% of adults aged over 65 years in North America have Type 2 diabetes mellitus (DM). Diabetes-induced osteoporosis (DM-OS) is caused by chronic hyperglycemia, advanced glycated end products and oxidative stress. The increase in the prevalence of DM-OS has prompted researchers to develop new biological therapies for the management of DM-OS.

Areas covered: This review covered the current and novel biological agents used in the management of DM-OS. Data were retrieved from PubMed, Scopus, American Diabetes Association and International Osteoporosis Foundation websites, and ClinicalTrials.gov. The keywords for the search included: DM, osteoporosis, and management.

Expert opinion: Several biological molecules have been examined in order to find efficient drugs for the treatment of DM-OS. These biological agents include anti-osteoporosis drugs: net anabolics (parathyroid hormone/analogs, androgens, calcilytics, anti-sclerostin antibody), net anti-resorptive osteoporosis drugs (calcitonin, estrogen, selective estrogen receptor modulators, bisphosphonates, RANKL antibody) and anti-diabetic drugs (alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones, GLP-1 receptor agonists, dipeptidylpeptidase-4 inhibitors, sodium glucose co-transporter-2 inhibitors, insulin). Biological medications that effectively decrease hyperglycemia and, at the same time, maintain bone health would be an ideal drug/drug combination for the treatment of DM-OS.     

Synthesis and biological evaluation studies of novel quinazolinone derivatives as antibacterial and anti-inflammatory agents

Some novel 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones bearing sulfonamide derivatives (4–11) were synthesized in good yields and evaluated for their possible antibacterial, anti-inflammatory activities and acute toxicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Their antibacterial activities were evaluated by the agar well diffusion method while their anti-inflammatory activities were evaluated by the carrageenan-induced hind paw edema test. All the tested compounds showed considerable antibacterial activities and high to moderate anti-inflammatory activities that last for 12 h compared to ibuprofen. All the tested compounds showed no toxic symptoms or mortality rates 24 h post-administration at tested anti-inflammatory doses. In addition, LD₅₀ for all tested compounds was higher than that for ibuprofen implying their good safety margin. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs.