Continent jejunal reservoir dialysis for end-stage renal disease: is it possible?

With limited organs available for renal transplantation in comparison with the number of patients on the waiting list, and with the drawbacks of dialysis, other forms of treatment for end-stage renal disease (ESRD) need to be investigated. We propose that using a reconfigured segment of bowel as a reservoir in which dialysate of various compositions can be instilled to remove metabolic wastes usually handled by the kidney may augment or replace renal function in a uremic patient. We have chosen the jejunum and have documented our preliminary findings using hyperosmotic dialysate along with the unique characteristics of continent jejunal reservoir dialysis (CJRD). With further refinements, CJRD may eventually be offered as an alternative treatment for ESRD.     

Synthesis and activity of phenyl derivatives containing 5,6-dimethylthieno[2,3-d]pyrimidin-4(1H)-one or 4H-pyrimido[5,4-b]indol-4-one heterocyclic system as potential nonsteroidal anti-inflammatory drugs

The synthesis, the analgesic and anti-inflammatory activities of two series of phenyl derivatives containing 5,6-dimethyl-thieno[2,3-d]pyrimidin-4(1H)-one and 4H-pyrimido[5,4-b]indol-4-one system, respectively, are reported. Two of these derivatives, 6A and 9B, showed interesting activities. The results of the pharmacological assays are discussed.     

Diurnal rhythms in intraocular pressure,axial length,and choroidal thickness in a primate model of eye growth,the common marmoset

PURPOSE. In chickens, there are circadian rhythms in axial length, choroidal thickness, and intraocular pressure (IOP), the phases of which differ, depending on visual manipulations that alter ocular growth rate. In this study, these same rhythms were sought in the common marmoset, a primate model of eye growth, to establish whether these may play a role in ocular growth regulation across species. METHODS. IOP was measured by applanation tonometry in 14 untreated marmosets ranging in age from 24 to 259 days. High-frequency A-scan ultrasonography was used to measure ocular dimensions (axial length and choroidal thickness) in 12 marmosets ranging in age from 24 to 572 days. Four monkeys were measured when they were juveniles (<110 days of age) and again later, when they were adolescents. Measurements were typically made at 12-hour intervals, although three animals were measured at 6-hour intervals. Nine monkeys had both IOP and axial dimensions measured in the same experiment. RESULTS. There was a diurnal rhythm in IOP in the marmosets: IOP was higher during the dark period and lower during the light period (mean change, 3.6 mm Hg; P < 0.005). There were also rhythms in axial length and choroidal thickness. The rhythm in axial length was dependent on age, with faster-growing eyes of juveniles increasing in length during the day and decreasing at night (+25 microm vs. -22 microm; P < 0.001) and slower-growing eyes of adolescents showing the opposite pattern (-27 microm vs. +46 microm; P < 0.0001). The choroid thickened during the night and thinned during the day, at all ages measured (+19 microm vs. -16 microm; P < 0.0001). CONCLUSIONS. Diurnal rhythms in IOP, axial length, and choroidal thickness exist in primates. Age-related differences in the phase relationships of these rhythms may be associated with differences in the rates of ocular growth.     

Oxidative stress and altered prostanoid production in the placenta of streptozotocin-induced diabetic rats

The oxidative stress in placental tissues during late pregnancy, as well as the relationship between reactive oxygen species (ROS) and the arachidonic acid (AA) pathway was evaluated in a neonatal streptozotocin (STZ)-induced diabetic rat model. Lipoperoxide levels are increased in diabetic tissues compared with control tissues (P<0.001) and they seem to increase throughout the development of gestation both in control (P<0.05) and STZ-induced diabetic (P<0.001) rats. Superoxide dismutase (SOD) activity is not modified on different days of pregnancy, but enzymatic activity is lower in diabetic tissues than in control tissues (P<0.01). Labour is preceded by an increase in placental 14C-prostaglandin conversion from 14C-AA in control and diabetic animals (P<0.05) and the thromboxane B2 (TXB2)/6-keto-prostaglandin F1alpha (PGF1alpha) ratio is higher in diabetic placental tissues than in controls. The addition of SOD and glutathione to the incubation medium does not modify prostanoid levels in control rats, but does decrease the AA conversion to PGF2alpha, PGE2 and TXB2 (P<0.05) in diabetic placenta. Superoxide radical generation (hypoxanthine/xanthine oxidase or hydrogen peroxide added to the incubation medium) produces a decrease in 6-keto-PGF1alpha (P<0.05) in control and diabetic tissues, whereas PGF2alpha, PGE2 and TXB2 levels, and PGF2alpha and TXB2 production are increased in control and diabetic animals respectively (P<0.05). Diabetic pregnant rats supplemented with a diet containing 400 mg day(-1) of alpha-tocopherol (vitamin E) have diminished placental PGF2alpha and TXB2 production and lipoperoxide levels. The results show a higher TXB2 and a decreased 6-keto-PGF1alpha placental production that may be linked to increased oxidative stress and to a reduced antioxidant capacity in STZ-induced diabetic rats. These imbalances, probably involved in abnormal placental structure and function, may potentially be corrected with dietary supplementation of alpha-tocopherol in diabetic pregnancies.     

Synthesis and evaluation of analogues of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine as inhibitors of tumor cell growth,trypanosomal growth,and HIV-1 infectivity

A well-defined series of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine analogues was designed and synthesized in order to further ascertain the optimal structural requirements for S-adenosylmethionine decarboxylase inhibition and potentially to augment and perhaps separate their antiproliferative and antitrypanosomal activities. Most structural modifications had a deleterious affect on both the antitrypanosomal and antineoplastic activity of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine. However, di-O-acetylation of the parent compound produced a potential prodrug that caused markedly pronounced inhibition of trypanosomal and neoplastic cell growth and viability. Moreover, the acetylated derivative of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine did inhibit HIV-1 growth and infectivity, whereas the parent compound did not.     

Evidence for a direct effect of captopril on early steps of insulin action in BC3H-1 myocytes

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been reported to improve insulin sensitivity. However, despite extensive investigation, the mechanisms responsible for this effect are not fully understood. Reduction of plasma angiotensin II and inhibition of kininase II have been suggested to contribute to improve insulin sensitivity. Insulin binding was measured at tracer insulin concentration in intact cells with or without captopril treatment. Specific binding, expressed as percent of total insulin added, was not different in control and captopril-treated cells. However, captopril treatment caused an increase in insulin-induced insulin receptor substrate-1 (IRS-1) phosphorylation accompanied by an increased association of IRS-1 with phosphoinositide-3 kinase (PI-3 kinase), despite no change on insulin receptor (IR) autophosphorylation. There was also an increased threonine kinase B (AKT) phosphorylation in captopril-treated cells followed by enhanced basal and insulin-stimulated glucose uptake. These results indicate that captopril treatment has a direct effect on early phosphorylation events induced by insulin in BC3H-1 myocytes.     

Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses

AIMS AND BACKGROUND: Up to now adjuvant chemotherapy after curative resection for gastric cancer (GC) has been considered an experimental approach. The results of existing phase III randomized trials comparing chemotherapy with control after surgery are controversial. Three meta-analyses have been published in recent years. It is likely that each of them presents a theoretical bias, mainly as regards the inclusion criteria of the trials. In this article we re-examine this potential bias, highlighting the differences between the present and past meta-analyses on adjuvant chemotherapy for GC. METHODS: Only randomized controlled clinical trials comparing systemic adjuvant chemotherapy with control after radical resection of GC were eligible. Total mortality was assessed as outcome measure of the treatment effect and a pooled odds ratio was calculated using the Peto-Mantel-Haenszel method. RESULTS: After the selection process 17 papers (18 comparisons) proved eligible for inclusion in the meta-analysis with a total of 3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the control arms; 762 and 871 deaths occurred in the treatment and control arms, respectively. Statistical analysis suggests an absence of significant heterogeneity between the trials and a significant advantage in survival for adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84). CONCLUSIONS: Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a significant survival advantage in patients with GC. However, this observation undoubtedly requires confirmation in large randomized controlled trials including cisplatin before adjuvant chemotherapy after curative resection for GC can be proposed for use in clinical practice.     

Marital status and eating disorders: an analysis of its relevance

Objectives: This study attempts to understand the clinical impact of marital status on the psychopathology and symptomatology of anorexia (AN) and bulimia nervosa (BN) patients. Method: Eating disorder (ED) patients (n=332, 198 BN and 134 AN) consecutively admitted to our unit participated in the study. All subjects met DSM-IV criteria for those pathologies and were female. Our sample was divided retrospectively into three subgroups based on their marital status. For the assessment, commonly applied questionnaires in the field of ED were used [Eating Attitudes Test (EAT-40), Eating Disorder Inventory (EDI), Bulimic Investigatory Test Edinburgh (BITE), Body Shape Questionnaire (BSQ), Beck Depression Inventory (BDI) and Social Avoidance and Distress Scale (SAD)]. Results: 2×3 (Diagnostic×Marital status) ANOVA and ANCOVA (with age as covariance) designs were applied in the current study. Our results suggested that ED patients who lived with a partner were significantly different with respect to the other ED patients in the following variables: higher age (P<.0001), higher motivation for change (P<.004), perfectionism (P<.03) and purging behavior (P<.04). Discussion: The main finding in this study is that ED patients who live with a partner are those who presented greater eating symptomatology and psychopathology but even higher motivation for change. Interpersonal functionality has to be considered in the development and maintenance of ED.     

Renal allograft laceration treated by superselective embolization.

PURPOSE: To report an illustrative case demonstrating the efficacy of endovascular treatment for traumatic blunt renal allograft injury. CASE REPORT: A 19-year-old man sustained an injury to his renal allograft after a traffic accident secondary to lap belt compression. Angiography revealed contrast extravasation from 2 disrupted upper pole renal artery branches, which were successfully embolized with microcoils. The creatinine level was transiently elevated to 4.1 mg/dL, but it improved to 2.9 mg/dL at discharge 13 days after admission. After 1 year, the serum creatinine level was 1.9 mg/dL. CONCLUSION: As in the native kidney, superselective embolization can also be used safely in the management of blunt injury to a renal allograft, avoiding surgery and preserving graft function.